Wtacid peptides for pancreatic cancer and lung cancer
Peptides targeting cancer cells with a CPP and SARS-CoV-2 spike SI fragment address the limited treatment options for pancreatic and lung cancers by inducing apoptosis and reducing tumor growth.
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- THE UNITED STATES OF AMERICA AS REPRESENTED BY THE DEPT OF VETERANS AFFAIRS
- Filing Date
- 2025-11-06
- Publication Date
- 2026-05-15
AI Technical Summary
Pancreatic and lung cancers have high mortality rates with limited treatment options, and existing chemotherapy is not effective, necessitating new therapeutic approaches.
Compositions and methods utilizing peptides comprising a cell-penetrating peptide (CPP) and a fragment of the SARS-CoV-2 spike SI peptide to increase LDH release, decrease mitochondrial metabolism, and induce apoptosis in cancer cells.
The peptides effectively target and induce cell death in pancreatic and lung cancer cells while sparing normal cells, leading to tumor regression and reduced angiogenesis in preclinical models.
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Figure US2025054323_15052026_PF_FP_ABST
Abstract
Description
wtACID PEPTIDES FOR PANCREATIC CANCER AND LUNG CANCERSTATEMENT REGARDING FEDERALLY SPONSORED RESEARCH
[0001] Tlii s invention was made with government support under VA award 1IK6 BX004982 awarded by the Department of Veterans Affairs. The government has certain rights in the invention.CROSS-REFERENCE TO RELATED APPLICATIONS
[0002] This Application claims the benefit of U. S. Application No. 63 / 717,692, filed on N ovember 07, 2024, the contents of which are incorporated herein by reference in its entirety7.REFERENCE TO SEQUENCE LISTING
[0003] This Application includes a Sequence Listing filed electronically as an XML file named “37759 0648P1 SL”, created on November 01, 2025, with a size of 11,644 bytes. The Sequence Listing is incorporated herein by reference in its entirety-.BACKGROUND
[0004] Pancreatic cancer is a very aggressive cancer with a high mortality rate and limited treatment options. It is the fourth leading cause of cancer in the US, and mortality rate is rising rapidly with a 12% relative 5-year survival rate. Cytotoxic chemotherapy has been the only viable systemic treatment option for patients with pancreatic cancer, especially in cases where surgery- is not an option. Similarly, lung cancer is also the leading cause of cancer related deaths worldwide, with a relatively low 5-year survival rate. Ironically, among all cancers, lung cancer is by far the leading cause of cancer death in which more than 130,000 people die each year in the USA. In fact, more people die of lung cancerthan of colon, breast and prostate cancers together, approximately am ounting to 25% of all cancer deaths in the USA. Therefore, new effective treatment options for lung cancer and pancreatic cancer are urgently needed.BRIEF SUMMARY
[0005] Described herein are compositions and methods for treating cancer and treating or ameliorating symptoms of cancer. Also described herein are compositions and methods forincreasing LDH release, decreasing MIT metabolism and inducing apoptosis in cancer cells.
[0006] Disclosed herein are peptides comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0007] Also disclosed herein are nucleic acid molecules capable of encoding the peptides disclosed herein. Also disclosed herein are nucleic acid molecules capable of encoding a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0008] Also disclosed herein are vectors comprising one or more of the nucleic acid molecules disclosed herein. Also disclosed are vectors comprising a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0009] Also disclosed herein are cells comprising one or more of the peptides, nucleic acid molecules or vectors disclosed herein. Disclosed herein are cells comprising a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide. Disclosed herein are cells comprising a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide. Disclosed herein are cells comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0010] Disclosed herein are compositions comprising one or more of the peptides, nucleic acid constructs, vectors or cells disclosed herein. Disclosed herein are compositions comprising a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide. Disclosed herein are compositions comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide. Disclosed herein are compositions comprising a vector comprising a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide. Disclosed herein are compositions comprising a cell, wherein the cell comprises a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0011] Also disclosed herein are pharmaceutical compositions comprising one or more of the peptides, nucleic acid constructs, vectors, cells or compositions disclosed herein.Disclosed herein are pharmaceutical compositions comprising a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide. Disclosed herein are pharmaceutical compositions comprising a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide. Disclosed herein are pharmaceutical compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide. Disclosed herein are pharmaceutical compositions comprising a cell, wherein the cell comprises a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide. Disclosed herein are pharmaceutical compositions comprising a composition, wherein the composition comprises a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0012] Disclosed herein are methods of treating cancer in a subject in need thereof comprising administering an effective amount of one or more of the peptides, nucleic acid molecules, vectors, cells, compositions or pharmaceutical compositions disclosed herein.
[0013] Disclosed herein are methods of increasing LDH release in a subject in need thereof comprising administering an effective amount of one or more of the peptides, nucleic acid constructs, vectors, cells, compositions or pharmaceutical compositions disclosed herein.
[0014] Disclosed herein are methods of decreasing MIT metabolism in a subject in need thereof comprising administering an effective amount of one or more of the peptides, nucleic acid constructs, vectors, cells, compositions or pharmaceutical compositions disclosed herein.
[0015] Disclosed herein are methods of inducing apoptosis of cancer cells in a subject in need thereof comprising administering an effective amount of one or more of the peptides, nucleic acid constructs, vectors, cells, compositions or pharmaceutical compositions disclosed herein.BRIEF DESCRIPTION OF THE DRAWINGS
[0016] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate several aspects of the disclosed method and compositions and together with the description, serve to explain the principles of the disclosed method and compositions.
[0017] FIG. 1 is a ri bbon diagram showing the interaction of the ACE2-InteractingDomain (ACID) of SARS-CoV-2 spike SI and ACE2.
[0018] FIGs. 2A-2D shows a wtACID peptide induces cell death in PANC-1 pancreatic cancer cells, but not HPDE normal pancreatic cells. PANC-1 (FIG. 2 A, FIG. 2B) and HPDE (FIG. 2C, FIG. 2D) cells were treated with different concentrations of wtACID and mACID peptides for 24 h under serum free condition followed by measuring LDH release (FIG, 2A, FIG. 2C) and MTT metabolism (FIG. 2B, FIG. 2D). Results are mean + SD of three different experiments. **p < 0.01; ***p < 0.001; NS, not significant with respect to control.
[0019] FIGs. 3A-3D show7wtACID peptide induces cell death in H1299 lung cancer cells, but not BEAS-2B normal lung epithelial cells. Hl 299 (FIG. 3 A, FIG. 3B) and BEAS-2B (FIG. 3C, FIG. 3D) cells were treated with different concentrations of wtACID and mACID peptides for 24 h under serum free condition followed by measuring LDH release (FIG. 3 A, FIG. 3C) and MTT metabolism (FIG. 3B, FIG. 3D), Results are mean + SD of three different experiments. **p < 0.01; ***p < 0.001; NS, not significant with respect to control.
[0020] FIGs. 4A-4B show- wtACID, but not mACID, peptide binds to ACE2 protein. Binding isotherm of ACE2 and ACID peptides were determined using surface plasmon resonance (SPR). Dose dependent response of wtACID (FIG. 4A) and mACID (FIG. 4B) were show:•
[0021] FIGs. 5 A-5F show that wtACID induces apoptosis in human pancreatic cancer cells PANC1 and BXPC3, but not normal pancreatic cells IIPDE. Cells were treated with 2pM of either wtACID or mACID peptide for 12 h followed by monitoring apoptosis by TUNEL assay (FIG. 5A, HPDE; FIG. 5B, BXPC3; FIG. 5C, PANCI). Cells were stamded to show apoptotic nuclei and total nuclei, respectively. Scale bar = 50pm. TUNEL-positive cells were counted in 2 images of each of three different experiments per group and presented as % of total D API-positive cells (FIG. 5D, HPDE; FIG. 5E, BXPC3; FIG. 5F, PANCI). Data are represented as the mean ± SD of three independent experiments, with statistical significance indicated as ****p < 0.0001; ns, not significant.
[0022] FIGs. 6A-6D show intranasal administration of wtACID leads to tumor regression in patientderived xenograft (PDX) model of pancreatic cancer. Female 6-8 week old NOD scid gamma (NSG) mice were engrafted with pancreatic ductal adenocarcinoma (PDAC) tumor fragments (TM01212) in the flank. When PDX mice (n:::3) tumors reached 50 mm2, mice were treated with wtACID (0.1 mg / kg body w7t / d) intranasally. During daily intranasal treatment, wtACID peptide was dissolved in 4 pl saline. After 4 eeks of treatment, tumors w7ere surgically removed from the flank of all mice (FIG. 6A). Three mice were included ineach group. FIG. 6B) Tumor size on the day of sacrifice is shown. FIG. 6C) Tumor sections were labeled for TUNEL. FIG. 6D) TUNEL positive cells were counted in 2 sections of each of 3 mice per group. ***p < 0.001.
[0023] FIGs. 7A-7B show intranasal administration of wtACID reduces angiogenesis marker VEGF in the tumor of PDX model of pancreatic cancer. Female 6-8 week old NSG mice were engrafted with PDAC tumor fragments (TM01212) in the flank. When PDX mice (n:==3) tumors reached 50 mm2, mice were treated with wtACID (0.1 mg / kg body wt / d) intranasally. FIG. 7A) After 4 weeks of treatment, tumor sections were immunostained for VEGF. FIG. 7B) VEGF positive cells were counted in 2 sections of each of 3 mice per group. ***p < 0.001.
[0024] FIGs. 8A-8B show intranasal administration of wtACID decreases angiogenesis marker VEGFR-2 in the tumor of PDX model of pancreatic cancer. Female 6-8 week old NSG mice were engrafted with PDAC tumor fragments (TM01212) in the flank. When PDX mice tumors reached 50 mm2, mice were treated with wtACID (0.1 mg / kg body wt / d) intranasally. FIG. 8A). After 4 weeks of treatment, tumor sections were immunostained for VEGFR-2. FIG. 8B) VEGFR-2 positive cells were counted in 2 sections of each of 3 mice per group. ***p < 0.001.
[0025] FIGs. 9A-9F show The wtACID peptide induces apoptosis in human lung cancer cells (A549 and H1299), but not normal human lung epithelial cells (BEAS-2B). BEAS-2B (FIG. 9A), A549 (FIG. 9B) and H1299 (FIG. 9C) cells were treated with 2 pM of w tACID or mACID peptides for 12 h under serum free condition followed by TUNEL staining. Scale bar = 50pm. DAPI w?as used to stain nuclei. TUNEL-positive cells were counted in 2 images of each of three different experiments per group and presented as % of total D APIpositive cells (FIG. 9D, BEAS-2B; FIG. 9E, A549; FIG. 9F, H1299). Results are mean t SD of three different experiments. ***p < 0.001; NS, not significant with respect to control.DETAILED DESCRIPTION
[0026] The disclosed methods and compositions may be understood more readily by reference to the follow ing detailed description of particular aspects and the Examples included therein and to the Figures and their previous and following description.
[0027] It is to be understood that the disclosed method and compositions are not limited to specific synthetic methods, specific analytical techniques, or to particular reagents unless otherwise specified, and, as such, may vary. It is also to be understood that the terminologyused herein is for the purpose of describing particular aspects only and is not intended to be limiting.A. Definitions
[0028] The terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting.
[0029] As used in the specification and the appended claims, the singular forms “a,” ” i i ’ and “the” can include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a compound” includes mixtures of compounds, reference to “a pharmaceutical carrier” includes mixtures of two or more such carriers, and the like.
[0030] The word “or” as used herein means any one member of a particular list and also includes any combination of members of that list.
[0031] Ranges may be expressed herein as from “about” one particular value, and / or to “about” another particular value. Tire term "about" is used herein to mean approximately, in the region of, roughly, or around. When the term "about" is used in conjunction with a numerical range, it modifies that range by extending the boundaries above and below7tire numerical values set forth. In general, the term “about” is used herein to modify a numerical value above and below the stated value by a variance of 20%. When such a range is expressed, another embodiment includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another embodiment. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint.
[0032] As used herein, the term “amino acid sequence” refers to a list of abbreviations, letters, characters or words representing amino acid residues. The amino acid abbreviations used herein are conventional one letter codes for the amino acids and are expressed as follows: A, alanine; C, cysteine; D aspartic acid; E, glutamic acid; F, phenylalanine; G, glycine; H histidine; I isoleucine; K, lysine; L, leucine; M, methionine; N, asparagine; P, proline; Q, glutamine; R, arginine; S, serine; T, threonine; V, valine; W, tryptophan; and Y, tyrosine. All alpha amino acids except glycine can exist in either of two enantiomers, called L-amino acids or D-amino acids, w hich are mirror images of each other.
[0033] As used herein, the term “amino acid” refers to an organic molecule with a basic amino group (-NH2), an acidic carboxyl group (-COOH), a proton and a variable ‘R’ group bound to an sp3 hybridized central carbon atom. Tire N-terminus of a peptide has a free amino group (-NH2). The C -terminus of a peptide has a free carboxyl group ( COOH).
[0034] “Peptide” as used herein refers to any peptide, oligopeptide, polypeptide, gene product, expression product, or protein, A peptide is compri sed of consecutive amino acids. The term “peptide” encompasses naturally occurring or synthetic molecules. A residue of a peptide is an amino acid. As used herein if an amino acid is said to be in the 5thposition, it is the 5thamino acid from the N-terminus of the peptide.
[0035] Tire term cell penetrating peptide (CPP) as used herein refers to a relatively short peptides, for example about 4 to about 40 amino acids, with the ability to gain the access to the cell interior by means of different mechanism, and / or with the capacity to promote the intracellular effects by themselves or by the delivered bioactive cargoes. CPPs facilitate cellular intake and uptake of molecules ranging from nanosize particles to small chemical compounds to large fragments of DM A. CPPs typically have an amino acid composition that either contains a high relative abundance of positively charged amino acids such as lysine or arginine or has sequences that contain an alternating pattern of polar, charged amino acids and non-polar, hydrophobic amino acids. These two types of structures are referred to as polycationic or amphipathic, respectively. A third class of CPPs are the hydrophobic peptides, containing only apolar residues with low net charge or hydrophobic amino acid groups that are crucial for cellular uptake.
[0036] By “fragment” is meant a portion of a polypeptide or nucleic acid molecule, such as, but not limited to, a truncation mutant. This portion contains, preferably, at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% of the entire length of the reference nucleic acid molecule or polypeptide. For example, a fragment of a polypeptide may contain about 5, about 10, about 15, about 20, about 25 or about 30 or more amino acids. In another example, a fragment of a polypeptide may contain about 1000, about 1500, about 2000, about 2500 or about 3000 or more amino acids.
[0037] As used herein, the term “epitope” refers to a localized region on the surface of an antigen capable of eliciting an immune response,
[0038] As used herein, “sample” is meant to mean an animal; a tissue or organ from an animal; a cell (either within a subject, taken directly from a subject, or a cell maintained in culture or from a cultured cell line); a cell lysate (or lysate fraction) or cell extract; or a solution containing one or more molecules derived from a cell or cellular material (e.g. a polypeptide or nucleic acid), which is assayed as described herein. A sample may also be any body fluid or excretion (for example, but not limited to, blood, urine, stool, saliva, tears, bile) that contains cells or cell components.
[0039] As used herein, “subject” refers to the target of administration, e.g. an animal.Thus the subject of the disclosed methods can be a vertebrate, such as a mammal. For example, the subject can be a human, Tire term does not denote a particular age or sex. Subject can be used interchangeably with “individual” or “patient”.
[0040] As used herein, “modulate” is meant to mean to alter, by increasing or decreasing.
[0041] As used herein, “isolated polypeptide” or “purified polypeptide” is meant to mean a polypeptide (or a fragment thereof) that is substantially free from the materials with which the polypeptide is normally associated in nature. The polypeptides of the invention, or fragments thereof, can be obtained, for example, by extraction from a natural source (for example, a mammalian cell), by expression of a recombinant nucleic acid encoding the polypeptide (for example, in a cell or in a cell-free translation system), or by chemically synthesizing the polypeptide. In addition, polypeptide fragments may be obtained by any of these methods, or by cleaving full length proteins and / or polypeptides.
[0042] “Dose” or “dosage” as used herein refers to a specific quantity of a therapeutic agent, such as a peptide, that is taken at specific times.
[0043] As used herein, “treat” is meant to mean administer one of the disclosed compositions to a subject, such as a human or other mammal (for example, an animal model), that has cancer, in order to prevent or delay a worsening of the effects of the disease or condition, such as cancer, or to partially or fully reverse the effects of a disease such as cancer.
[0044] As used herein, “prevent” is meant to mean minimize the chance that a subject will develop cancer.
[0045] As used herein, the term “treatment cycle” refers to the administration of a peptide for an established period of time. A treatment cycle includes a wide range of dosages of peptide as well as different lengths of time for administering one or more of the peptides, nucleic acid constructs, vectors, cells, compositions or pharmaceutical compositions disclosed herein. For example, a treatment cycle can be a three month period wherein one of the peptides disclosed herein is administered twice a week for the three month period.
[0046] As used herein, “effective amount” is meant to mean a sufficient amount of one or more of the peptides, nucleic acid constructs, vectors, cells, compositions or pharmaceutical compositions disclosed herein to provide the desired effect. For example, an effective amount of one or more of the peptides, nucleic acid constructs, vectors, cells, compositions or pharmaceutical compositions disclosed herein can be an amount that provides a therapeutic affect and provides sustained therapeutic effects after withdrawal of the treatment. An effective amount of one or more of the peptides, nucleic acid constructs, vectors, cells,compositions or pharmaceutical compositions disclosed herein can be an amount that is able to cause a benefit illustrated by a reduction in cancer, or the effects of cancer, an increase in LDH release, a decrease in MIT metabolism and / or an increase in apoptosis of cancer cells, as well as an amount that allows for a sustained therapeutic effect after withdrawal of tire peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition. The exact amount required will vary from subject to subject, depending on the species, age, and general condition of the subject, the severity of disease (or underlying genetic defect) that is being treated, the particular compound used, its mode of administration, and the like. Thus, it is not possible to specify an exact “effective amount.” However, an appropriate “effective amount” may be determined by one of ordinary skill in the art using only routine experimentation.
[0047] As used herein, “sustained therapeutic effect” is a therapeutic effect that persists after the therapeutic has been withdrawn. For example, the sustained therapeutic effect is maintained even after the peptide, nucleic acid, vector, composition or pharmaceutical composition is no longer being administered.
[0048] The phrase “nucleic acid” as used herein refers to a naturally occurring or synthetic oligonucleotide or polynucleotide, whether DNA or RNA or DNA-RNA hybrid, single-stranded or double-stranded, sense or antisense, which is capable of hybridization to a complementary nucleic acid by Watson-Crick base-pairing. Nucleic acids of the invention can also include nucleotide analogs (e.g., BrdU), and non-phosphodiester intemucleoside linkages (e.g., peptide nucleic acid (PNA) or thiodiester linkages). In particular, nucleic acids can include, without limitation, DNA, RNA, cDNA, gDNA, ssDNA, dsDNA or any combination thereof.
[0049] The terms “vector” or “construct” refer to a nucleic acid sequence capable of transporting into a cell another nucleic acid to which the vector sequence has been linked. The term "expression vector" includes any vector, (e.g,, a plasmid, cosmid or phage chromosome) containing a gene construct in a form suitable for expression by a cell (e.g., linked to a transcriptional control element). "Plasmid" and "vector" are used interchangeably, as a plasmid is a commonly used form of vector. Moreover, the invention is intended to include other vectors which serve equivalent functions.
[0050] The term “expression vector” is herein to refer to vectors that are capable of directing the expression of genes to which they are operatively -linked. Common expression vectors of utility in recombinant DNA techniques are often in the form of pl smids.Recombinant expression vectors can comprise a nucleic acid as disclosed herein in a formsuitable for expression of the acid in a host cell. In other words, the recombinant expression vectors can include one or more regulator ’ elements or promoters, which can be selected based on the host cells used for expression that is operatively linked to the nucleic acid sequence to be expressed.
[0051] As used herein, “treating cancer” means a decrease or reduction in any cancer or cancer-mediated effect on a subject or decreasing the size of tumor or alleviating or removing a symptom of cancer in the subject, including, but not limited to, cancer-induced cell growth, cancer-induced changes in LDH release, and / or cancer-induced changes in MTT metabolism.
[0052] Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of skill in the art to which the disclosed method and compositions belong. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present method and compositions, the particularly useful methods, devices, and materials are as described.Publications cited herein and the material for which they are cited are hereby specifically incorporated by reference. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such disclosure by virtue of prior invention. No admission is made that any reference constitutes prior art. The discussion of references states what their authors assert, and applicants reserve the right to challenge the accuracy and pertinency of the cited documents. It will be clearly understood that, although a number of publications are referred to herein, such reference does not constitute an admission that any of these documents forms part of the common general knowledge in the art.B. Compositions1. Peptides
[0053] Non-limiting examples of the peptides of the disclosure are provided herein. Disclosed herein are peptides comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide,
[0054] In some aspects, the CPP is at the N terminus of the peptide. In some aspects, the CPP is at the C terminus of the peptide.
[0055] In some aspects, the CPP is cationic. In some aspects, the CPP is non-amphipathic.
[0056] In some aspects, the CPP is the cell-penetrating domain of HIV-1 Tat. In some aspects, the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: 1). In some aspects, the CPP is polyarginine RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3). In some aspects, the CPP is antennapedia homeodomainDRQIKIWFQNRRMKWKK (SEQ ID NO: 4). In some aspects, the CPP is YARAAARQARA (SEQ ID NO: 1). In some aspects, the CPP is not YARAAARQARA (SEQ ID NO: 1).
[0057] In some aspects, the fragment of SARS-CoV-2 spike SI is from about 10 to 20 amino acids long.
[0058] In some aspects, the fragment of SARS-CoV-2 spike SI is from 12 to 18 amino acids long. In some aspects, the fragment of SARS-CoV-2 spike SI is from about 12 to 15 amino acids long.
[0059] In some aspects, the fragment of SARS-CoV-2 spike SI is 10 amino acids long. In some aspects, the fragment of SARS-CoV-2 spike S 1 is 11 amino acids long. In some aspects, the fragment of SARS-CoV-2 spike SI is 12 amino acids long. In some aspects, the fragment of SARS-CoV-2 spike SI is 13 amino acids long. In some aspects, the fragment of SARS-CoV-2 spike SI is 14 amino acids long. In some aspects, the fragment of SARS-CoV-2 spike SI is 15 amino acids long. In some aspects, the fragment of SARS-CoV-2 spike SI is 16 amino acids long. In some aspects, the fragment of SARS-CoV-2 spike SI is 17 amino acids long. In some aspects, the fragment of SARS-CoV-2 spike SI is 18 amino acids long. In some aspects, the fragment of SARS-CoV-2 spike SI is 19 amino acids long. In some aspects, the fragment of SARS-CoV-2 spike SI is 20 amino acids long.
[0060] In some aspects, the fragment of SARS-CoV-2 spike SI comprises all or part of the ACE2-Interacting Domain (ACID) of SARS-CoV-2 spike SI. In some aspects, the fragment of ACE2 -Interacting Domain (ACID) of SARS-CoV-2 spike SI comprises the sequence QSYGFQPTNGVGY (SEQ ID NO: 5). In some aspects, the fragment of ACE2-Interacting Domain (ACID) of SARS-CoV-2 spike SI comprises the sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects, the fragment of ACE2 -Interacting Domain (ACID) of SARS-CoV-2 spike SI does not comprise the sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence NGVGY (SEQ ID NO: 7). In some aspects, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence GGVGD (SEQ ID NO: 8), In some aspects, the disclosed peptides can comprise one or more of the sequences of Table 1. For example, disclosed herein are peptides comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. In some aspects, the peptides comprise SEQ ID NO: 11.Table 1 - Peptides and Peptide Fragments
[0061] In some aspects, the disclosed peptides can be made synthetically or recombinantly.
[0062] In some aspects, the disclosed peptides further comprise a targe ting domain. In some aspects, the targeting domain is at the N terminus of the peptide. In some aspects, the targeting domain is at the C terminus of the peptide, hi some aspects, the targeting domain is ACE2.2. Variants
[0063] Also disclosed a variants or derivatives of the peptides disclosed herein. Nonlimiting examples of the peptides have been described herein (see Table I, for example). For example, disclosed herein are peptides comprising a fragment of ACE2-Interacting Domain (ACID) of SARS-CoV-2 spike SI, wherein the fragment of ACE2 -Interacting Domain (ACID) of SARS-CoV-2 spike SI comprises a sequence having 70%, 75%, 80%, 85%, 90%, or 95% identity to SEQ ID NO: 5 or SEQ ID NO: 6. In some aspects, the fragment of SARS-CoV-2 spike SI comprises one, two, three, four or five amino acid substitutions as compared to SEQ IDNO: 5. In some aspects, the fragment of SARS-CoV-2 spike SI comprises an ammo acid substitution at position 2, 9 or 13 of SEQ ID NO: 5. In some aspects, the fragment of SARS-CoV-2 spike SI comprises an amino acid substitution at position 2, 9 and 13 of SEQ ID NO: 5. In some aspects, the fragment of SARS-CoV-2 spike SI comprises at least 70% identity to SEQ ID NO: 5 and comprises substitutions at S, N and Y amino acids at position 2, 9 or 13 of SEQ ID NO: 5. As used herein, the term “analog” is used interchangeably with “variant” and “derivative.” Variants and derivatives are well understood to those of skill in the art and can involve amino acid sequence modifications. Such amino acid sequence modifications typically fall into one or more of three classes: substantial; insertional; or deletional variants. Insertions include amino and / or carboxyl terminal fusions as well as intrasequence insertions of single or multiple amino acid residues. Insertions ordinarily are smaller insertions than those of ammo or carboxyl terminal fusions, for example, on the order of one to four residues. These variants ordinarily are prepared bysite-specific mutagenesis of nucleotides in the DNA encoding the protein, thereby producing DNA encoding the variant, and thereafter expressing the DNA in recombinant cell culture. Techniques for making substitution mutations at predetermined sites in DNA having a known sequence are well known, for example M13 primer mutagenesis and PCR mutagenesis. Amino acid substitutions are typically of single residues, but can occur at a number of different locations at once. Substitutions, deletions, insertions or any combination thereof may be combined to arrive at a final derivative or analog. Substitutional variants are those in which at least one residue has been removed and a different residue inserted in its place. Such substitutions generally are made in accordance with Tables 3 and 4 and are referred to as conservative substitutions.
[0064] Substantial changes in function or immunological identity are made by selecting substitutions that are less conservative than those in Table 3, i.e., selecting residues that differ more significantly in their effect on maintaining (a) the structure of the polypeptide backbone in the area of the substitution, for example as a sheet or helical conformation, (b) the charge or hydrophobicity of the molecule at the target site, or (c) the bulk of the side chain. The substitutions which in general are expected to produce the greatest changes in the protein properties are those in which: (a) the hydrophilic residue, e.g. seryl or threonyl, is substituted for (or by) a hydrophobic residue, e.g., leucyl, isoleucyl, phenylalanyl, valyl or alanyl;Tryptophan, Tyrosinyl (b) a cysteine or proline is substituted for (or by) any? other residue; (c) a residue having an electropositive side chain, e.g., lysyl, arginyl, or hystidyl, is substituted for (or by) an electronegative residue, e.g. glutamyl or aspartyl; or (d) a residue having a bulky side chain, e.g., phenylalanine, is substituted for (or by) one not having a side chain, e.g., glycine, in this case, or (e) by increasing the number of sites for sulfation and / or glycosylation.Table 3 Amino Acid SubstitutionsTable 4: Amino Acid Abbreviations
[0065] It is understood that one way to define the variants and derivatives of the disclosed proteins herein is to define them in terms of homology / identity to specific known sequences. Specifically disclosed are variants of peptides h erein disclosed which have at least, 70% or at least 75% or at least 80% or at least 85% or at least 90% or at least 95% or at least 96% or at least 97% or at least 98% or at least 99% identity to the peptides specifically recited herein. For example, disclosed are variants of the peptides herein disclosed which have at least 70% or at least 75% or at least 80% or at least 85% or at least 90% or at least 95% or at least 96% or at least 97% or at least 98% or at least 99% identity to SEQ ID MO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. Also, disclosed are variants of the peptides herein comprising a fragment of SARS-CoV-2 spike SI disclosed, which have at least 70% or at least 75% or at least 80% or at least 85% or at least 90% or at least 95% or at least 96% or at least 97% or at least 98% or at least 99% identity to SEQ ID NO: 5 or 6. Those of skill in the art readily understand how to determine the identity of two proteins.
[0066] The polypeptides disclosed herein can be modified by either natural processes, such as post-translational processing, or by chemical modification techniques which are well known in the art. Modifications can occur anywhere in the polypeptide, including the peptide backbone, the amino acid side-chains and the amino or carboxyl termini. The same type of modification can be present in the same or varying degrees at several sites in a given polypeptide. Also, a given polypeptide can have many types of modifications. Modifications include, without limitation, acetylation, acylation, ADP-ribosylation, amidation, covalent cross-linking or cyclization, covalent attachment of flavin, covalent attachment of a heme moiety, covalent attachment of a nucleotide or nucleotide derivative, covalent attachment of a lipid or lipid derivative, covalent attachment of a phosphatidylinositol, disulfide bond formation, demethylation, formation of cysteine or pyroglutamate, formylation, gammacarboxylation, glycosylation, GPI anchor formation, hydroxylation, iodination, methylation, myristolyation, oxidation, pegylation, proteolytic processing, phosphorylation, prenylation,racemization, selenoylation, sulfation, and transfer-RNA mediated addition of amino acids to protein such as arginylation. (See Proteins - Structure and Molecular Properties 2nd Ed., T. E. Creighton, W. H. Freeman and Company, New York (1993); Posttranslational Covalent Modification of Proteins, B. C. Johnson, Ed., Academic Press, New York, pp. 1-12 (1983)).3. Nucleic Acids
[0067] As this specification discusses various peptide sequences it is understood that the nucleic acids that can encode those polypeptide sequences are also disclosed. This would include all degenerate sequences related to a specific polypeptide sequence, i.e. all nucleic acids having a sequence that encodes one particular polypeptide sequence as well as all nucleic acids, including degenerate nucleic acids, encoding the disclosed variants and derivatives of the protein sequences. Thus, while each particular nucleic acid sequence may not be written out herein, it is understood that each and every sequence is in fact disclosed and described herein through the disclosed polypeptide sequences.
[0068] Disclosed are nucleic acid molecules capable of encoding any of the peptides described herein.
[0069] Disclosed are nucleic acid molecules capable of encoding a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0070] In some aspects, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the CPP is at the N terminus of the peptide. For example, disclosed are nucleic acid molecules that encode a peptide having the amino acid sequence set forth in SEQ ID NOs: 1-12, In some aspects, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the CPP is at the C terminus of the peptide.
[0071] In some aspects, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the CPP is cationic. In some aspects, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the CPP is n on-amphipathic,
[0072] In some aspects, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the CPP is the cell-penetrating domain of HIV- 1 Tat. hi some aspects, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the CPP comprises the amino acid sequenceYARAAARQARA (SEQ ID MO: 1). In some aspects, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike Si peptide, wherein tire CPP is antennapediahomeodomain DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
[0073] hi some aspects, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the fragment of SARS-CoV-2 spike SI is about 10-20 amino acids long. In some aspects, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the fragment of SARS-CoV-2 spike SI is about 12-15 amino acids long.
[0074] In some aspects, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the fragment of SARS-CoV-2 spike SI comprises all or part of the ACE2 -Interacting Domain (ACID) of SARS-CoV-2 spike SI. In some aspects, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the fragment of SARS-CoV-2 spike SI composes the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). In some aspects, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence NGVGY (SEQ ID NO: 7). In some aspects, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence GGVGD (SEQ ID NO: 8).
[0075] In some aspects, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the fragment of SARS-CoV-2 spike SI comprises all or part of the ACE2-Interacting Domain (ACID) of SARS-CoV-2 spike SI. In some aspects, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6).
[0076] In some aspects, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the fragment of SARS-CoV-2 spike SI comprises all or part of the ACE2-Interacting Domain (ACID) of SARS-CoV-2 spike SI. In some aspects, the nucleic acid molecule encodes apeptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the fragment of SARS-CoV-2 spike SI comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y. In some aspects, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence NGVGY (SEQ ID NO: 7). In some aspects, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). In some aspects, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects, the nucleic acid molecule encodes a peptide wherein the peptide comprises one or more of the sequences of Table 1. For example, disclosed herein are nucleic acid molecules capable of encoding a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, or SEQ ID NO: 12. Disclosed herein are nucleic acid molecules capable of encoding a peptide comprising SEQ ID NO: 11.
[0077] In some aspects, the nucleic acid molecule encodes a peptide further comprising a targeting domain. In some aspects, the nucleic acid molecule encodes a peptide wherein the targeting domain is at the N terminus of the peptide. In some aspects, the nucleic acid molecule encodes a peptide wherein the targeting domain is at the C terminus of the peptide. In some aspects, the nucleic acid molecule encodes a peptide further comprising a targeting domain, wherein the targeting domain is ACE2.4. Vectors
[0078] Disclosed are vectors comprising a nucleic acid molecule capable of encoding any of the peptides disclosed herein.
[0079] For example, disclosed are vectors comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0080] In some aspects, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the CPP is at the N terminus of the peptide. In some aspects, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the CPP is at the C terminus of the peptide.
[0081] hi some aspects, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the CPP is cationic. In some aspects, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the CPP is non-amphipathic.
[0082] In some aspects, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the CPP is the cell-penetrating domain of HIV-1 Tat, In some aspects, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: 1).
[0083] hi some aspects, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the CPP is antennapedia homeodomain DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
[0084] In some aspects, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the fragment of SARS-CoV-2 spike SI is about 10 to about 20 amino acids long. In some aspects, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the fragment of SARS-CoV-2 spike SI is about 12 to about 20 amino acids long.
[0085] In some aspects, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the fragment of SARS-CoV-2 spike S 1 comprises all or part of the ACE2-Interacting Domain (ACID) of SARS-CoV-2 spike SI.
[0086] hi some aspects, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the fragment of SARS-CoV-2 spike S 1 comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y. In some aspects, tlie vectors comprise a nucleic acid molecule capable of encoding a peptide wherein die fragment of SARS-CoV-2 spike S I comprises the amino acid sequence NGVGY (SEQ ID NO: 7). In some aspects, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein die fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). hi some aspects, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the peptide comprises one or more of the sequences of Table 1. For example, disclosed herein are vectors comprising a nucleic acid molecule capable of encoding a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ IDNO: 11 or SEQ ID NO: 12. In some aspects, the vector comprises a nucleic acid molecule capable of encoding a peptide comprising SEQ ID NO: 11. In some aspects, the vectors comprise a nucleic acid molecule capable of encoding a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide and further comprising a targeting domain. In some aspects, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the targeting domain is at the N terminus of the peptide, in some aspects, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the targeting domain is at the C terminus of the peptide. In some aspects, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the targeting domain is ACE2.
[0087] Vectors that can be used herein can include plasmids, cosmids, and viruses (e.g., bacteriophage, animal viruses, and plant viruses), and artificial chromosomes (e.g., YACs). Vectors can comprise targeting molecules. A targeting molecule is one that directs the desired nucleic acid to a particular organ, tissue, cell, or other location in a subject's body. A vector, generally, brings about replication when it is associated with the proper control elements (e.g., a promoter, a stop codon, and a polyadenylation signal). Examples of vectors that are routinely used in the art include plasmids and viruses. The term “vector” includes expression vectors and refers to a vector containing a nucleic acid sequence coding for at least part of a gene product capable of being transcribed. A variety of ways can be used to introduce an expression vector into cells. In some aspects, the expression vector comprises a virus or an engineered vector derived from a viral genome. As used herein, “expression vector” is a vector that includes a regulatory’ region, A variety of host / expression vector combinations can be used to express the nucleic acid sequences disclosed herein. Examples of expression vectors include but are not limited to plasmids and viral vectors derived from, for example, bacteriophages, retroviruses (e.g., lentiviruses), and other viruses (e.g., adenoviruses, poxviruses, herpesviruses, baculovirus, tobacco mosaic virus and adeno-associated viruses). Vectors and expression systems are commercially available and known to one skilled in the art.5. Cells
[0088] As this specification discusses various peptide sequences and nucleic acid constructs, it is understood that cells comprising peptides and / or the nucleic acid constructs that can encode those polypeptide sequences are also disclosed.
[0089] Disclosed are cells comprising a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0090] hi some aspects of the cells comprising a peptide, the CPP is at the N terminus of the peptide. In some aspects of the cells comprising a peptide, the CPP is at the C terminus of the peptide.
[0091] In some aspects of the cells comprising a peptide, the CPP is cationic. In some aspects of the cells comprising a peptide, the CPP is non-amphipathic.
[0092] In some aspects of the cells comprising a peptide, the CPP is the cell-penetrating domain of HIV- 1 Tat. hi some aspects of the cells comprising a peptide, the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: 1). In some aspects of the cells comprising a peptide, the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the cells comprising a peptide, the CPP is antennapedia homeodomain DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
[0093] In some aspects of the cells comprising a peptide, the fragment of SARS-CoV-2 spike SI is from about 10 to 20 amino acids long.
[0094] In some aspects of the cells comprising a peptide, the fragment of SARS-CoV-2 spike SI is from 12 to 18 amino acids long, hi some aspects of the cells comprising a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to 15 amino acids long.
[0095] In some aspects of the cells comprising a peptide, the fragment of SARS-CoV-2 spike S I comprises all or part of the ACE2-Interacting Domain (ACID) of SARS-CoV-2 spike S 1. In some aspects of the cells composing a peptide, the fragment of SARS-CoV-2 spike SI comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y In some aspects of the cells comprising a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence NGVGY (SEQ ID NO: 7). In some aspects of the cells comprising a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). In some aspects of the cells comprising a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects of the cells comprising a peptide, the peptide is one or more of the sequences of Table 1. For example, disclosed herein are cells comprising a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. In some aspects, the cells comprise a peptide comprising SEQ ID NO: 11.
[0096] In some aspects of the cells comprising a peptide, the disclosed peptides further comprise a targeting domain. In some aspects of the cells comprising a peptide, the targeting domain is at the N terminus of the peptide. In some aspects of the cells comprising a peptide, the targeting domain is at the C terminus of the peptide. In some aspects of the cellscomprising a peptide, the targeting domain is ACE2
[0097] Disclosed are cells comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0098] Tn some aspects of the cells comprising nucleic acid molecules capable of encoding a peptide, the CPP is at the N terminus of the peptide. In some aspects of the cells comprising nucleic acid molecules capable of encoding a peptide, the CPP is at the C terminus of the peptide.
[0099] In some aspects of the cells comprising nucleic acid molecules capable of encoding a peptide, the CPP is cationic. In some aspects of the cells comprising nucleic acid molecules capable of encoding a peptide, the CPP is non-amphipathic.
[0100] Tn some aspects of the cells comprising nucleic acid molecules capable of encoding a peptide, the CPP is the cell-penetrating domain of HIV-1 Tat. In some aspects of the cells comprising nucleic acid molecules capable of encoding a peptide, the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: 1). In some aspects of the cells comprising nucleic acid molecules capable of encoding a peptide, the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the cells comprising nucleic acid molecules capable of encoding a peptide, the CPP is antennapedia homeodomain DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
[0101] In some aspects of the cells comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI is from about 10 to 20 amino acids long.
[0102] In some aspects of the cells comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI is from 12 to 18 amino acids long. In some aspects of the cells comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike S 1 is from about 12 to 15 amino acids long,
[0103] In some aspects of the cells comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike S 1 comprises all or part of the ACE2-Tnteracting Domain (ACID) of SARS-CoV-2 spike SI. In some aspects of the cells comprising nucleic acid molecules capable of encoding a peptide, the fragmen t of SARS-CoV-2 spike SI comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y. In some aspects of the cells comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence NGVGY (SEQ ID NO: 7). In someaspects of the cells comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). In some aspects of the cells comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects of the cells comprising nucleic acid molecules capable of encoding a peptide, the peptide is one or more of the sequences of Table 1. For example, disclosed herein are cells comprising a nucleic acid molecule encoding a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. In some aspects, the cells comprise a nucleic acid molecule encoding a peptide comprising SEQ ID NO: 11.
[0104] In some aspects of the cells comprising nucleic acid molecules capable of encoding a peptide, the disclosed peptides further comprise a targeting domain. In some aspects of the cells comprising nucleic acid molecules capable of encoding a peptide, the targeting domain is at the N terminus of the peptide. In some aspects of the cells comprising nucleic acid molecules capable of encoding a peptide, the targeting domain is at the C terminus of the peptide. In some aspects of the cells comprising nucleic acid molecules capable of encoding a peptide, the targeting domain is ACE2.6. Compositions
[0105] Disclosed herein are compositions comprising the peptides, nucleic acid constructs, vectors and cells disclosed herein.
[0106] For example, disclosed are compositions comprising a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0107] In some aspects of the compositions comprising a peptide, the CPP is at the N terminus of the peptide. In some aspects of the compositions comprising a peptide, the CPP is at the C terminus of the peptide.
[0108] In some aspects of the compositions comprising a peptide, the CPP is cationic, hi some aspects of the compositions comprising a peptide, the CPP is non-amphipathic.
[0109] In some aspects of the compositions comprising a peptide, the CPP is the cellpenetrating domain of HIV- 1 Tat. In some aspects of the compositions comprising a peptide, the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: 1). hi some aspects of the compositions comprising a peptide, the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the compositions comprising a peptide, the CPP is antennapedia homeodomain DRQIKIWFQNRRMKWKK(SEQ ID NO: 4).
[0110] In some aspects of the compositions comprising a peptide, the fragment of SARS-CoV-2 spike SI is from about 10 to 20 amino acids long.
[0111] In some aspects of the compositions comprising a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to about 18 ammo acids long. In some aspects of the compositions comprising a peptide, the fragment of SARS-CoV-2 spike S 1 is from about 12 to about 15 amino acids long.
[0112] hi some aspects of the compositions comprising a peptide, the fragment of SARS-CoV-2 spike SI comprises all or part of the ACE2-Interacting Domain (ACID) of SARS-CoV -2 spike S 1. In some aspects of the compositions comprising a peptide, the fragment of SARS-CoV-2 spike SI comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y. In some aspects of the compositions comprising a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence NGVGY (SEQ ID NO: 7). In some aspects of the compositions comprising a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). In some aspects of the compositions comprising a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects of the compositions comprising a peptide, the peptide is one or more of the sequences of Table 1. For example, disclosed herein are compositions comprising a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. In some aspects, the compositions comprise a peptide comprising SEQ ID NO: 11.
[0113] In some aspects of the compositions comprising a peptide, the disclosed peptides further comprise a targeting domain. In some aspects of the compositions comprising a peptide, the targeting domain is at the N tenninus of the peptide. In some aspects of the compositions comprising a peptide, the targeting domain is at the C terminus of the peptide. In some aspects of the compositions comprising a peptide, the targeting domain is ACE2.
[0114] Disclosed are compositions comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0115] In some aspects of the compositions comprising nucleic acid molecules capable of encoding a peptide, the CPP is at the N tenninus of the peptide. In some aspects of the compositions comprising nucleic acid molecules capable of encoding a peptide, the CPP is at the C terminus of the peptide.
[0116] hi some aspects of the compositions comprising nucleic acid molecules capable of encoding a peptide, the CPP is cationic. In some aspects of the compositions comprising nucleic acid molecules capable of encoding a peptide, the CPP is non-amphipathic.
[0117] In some aspects of the compositions comprising nucleic acid molecules capable of encoding a peptide, the CPP is the cell-penetrating domain ofHTV-1 Tat. In some aspects of the compositions comprising nucleic acid molecules capable of encoding a peptide, the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: 1). In some aspects of the compositions comprising nucleic acid molecules capable of encoding a peptide, the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the compositions comprising nucleic acid molec ules capable of encoding a peptide, the CPP is antennapedia homeodomain DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
[0118] In some aspects of the compositions comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI is from about 10 to 20 amino acids long.
[0119] In some aspects of the compositions comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to about 18 amino acids long. In some aspects of the compositions comprising nucleic acid molecules capable of encoding a peptide, the fragment of S ARS-CoV-2 spike S I is from about 12 to about 15 amino acids long.
[0120] hi some aspects of the compositions comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike S 1 comprises all or part of the ACE2-In teracting Domain (ACID) of SARS-CoV-2 spike SI. In some aspects of the compositions comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined ammo acids S, N and Y. In some aspects of the compositions comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence NGVGY (SEQ ID NO: 7). In some aspects of the compositions comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). In some aspects of the compositions comprising nucleic acid molecules capable of encoding a peptide, tire fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects of the compositions comprising nucleic acid molecules capable of encoding apeptide, the peptide is one or more of the sequences of Table 1. For example, disclosed herein are compositions comprising nucleic acid molecules capable of encoding a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. Disclosed herein are compositions comprising nucleic acid molecules capable of encoding a peptide comprising SEQ ID NO: 11.
[0121] In some aspects of the compositions comprising nucleic acid molecules capable of encoding a peptide, the disclosed peptides further comprise a targeting domain. In some aspects of the compositions comprising nucleic acid molecules capable of encoding a peptide, the targeting domain is at the N terminus of the peptide. In some aspects of the compositions comprising nucleic acid molecules capable of encoding a peptide, the targeting domain is at the C terminus of the peptide. In some aspects of the compositions comprising nucleic acid molecules capable of encoding a peptide, the targeting domain is ACE2.
[0122] Disclosed are compositions comprising vectors, wherein the vectors comprise a nucleic acid molecule capable of encoding any of the peptides disclosed herein.
[0123] For example, disclosed are compositions comprising vectors, wherein the vectors comprise a nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0124] In some aspects of the compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP is at the N terminus of the peptide. In some aspects of the compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP is at the C terminus of the peptide.
[0125] In some aspects of the compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP is cationic. In some aspects of the compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP is non-amphipathic.
[0126] hi some aspects of the compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP is the cellpenetrating domain of HIV- 1 Tat. In some aspects of the compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: 1).
[0127] In some aspects of the compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP is polyarginine(RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of tire compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP is antennapedia homeodomain DRQIK1WFQNRRMKWKK (SEQ ID NO: 4).
[0128] In some aspects of the compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV -2 spike SI is about 10 to about 20 amino acids long, hi some aspects of the compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike S I is about 12 to about 20 amino acids long.
[0129] In some aspects of the compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV -2 spike S 1 comprises all or part of the ACE2-Interacting Domain (ACID) of SARS-CoV -2 spike S 1.
[0130] hi some aspects of the compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y. In some aspects of the compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence NGVGY (SEQ ID NO: 7). In some aspects of the compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). In some aspects of the compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike S I comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects of the compositions comprising a vector, wherein the vector encodes a nucleic acid molecule capable of encoding a peptide, the peptide is one or more of the sequences of Table 1. For example, disclosed herein are compositions comprising a vector, wherein the vector encodes a nucleic acid molecule capable of encoding a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. Disclosed herein are compositions comprising a vector, wherein the vector encodes a nucleic acid molecule capable of encoding a peptide comprising SEQ ID NO: 11.
[0131] hi some aspects of the compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the peptide further comprises a targeting domain. In some aspects of the compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the targeting domain is at the N terminus of the peptide. In some aspects of the compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the targeting domain is at the C te minus of the peptide. In some aspects of the compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the targeting domain is ACE2.
[0132] Disclosed are compositions comprising cells, wherein the cells comprise a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike S 1 peptide,
[0133] In some aspects of the compositions comprising cells, wherein the cells comprise a peptide, the CPP is at the N terminus of the peptide. In some aspects of the compositions comprising cells, wherein the cells comprise a peptide, the CPP is at the C terminus of the peptide.
[0134] In some aspects of the compositions comprising cells, wherein the cells comprise a peptide, the CPP is cationic. In some aspects of the compositions comprising cells, wherein the cells comprise a peptide, the CPP is non-amphipathic.
[0135] In some aspects of the compositions comprising cells, wherein the cells comprise a peptide, the CPP is tire cell -penetrating domain of HIV- 1 Tat. In some aspects of the compositions comprising cells, wherein the cells comprise a peptide, the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: 1). In some aspects of the compositions comprising cells, wherein the cells comprise a peptide, the CPP is polyarginine (RRRRRRR RR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the compositions composing cells, wherein the cells comprise a peptide, the CPP is antennapedia homeodomain DRQIK1WFQNRRMKWKK (SEQ ID NO: 4).
[0136] In some aspects of the compositions comprising cells, wherein the cells comprise a peptide, the fragment of SARS-CoV-2 spike SI is from about 10 to 20 amino acids long.
[0137] In some aspects of the compositions comprising cells, wherein the cells comprise a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to about 18 amino acids long. In some aspects of the compositions comprising cells, wherein the cells comprise a peptide, the fragment of SARS-CoV-2 spike S 1 is from about 12 to about 15 amino acids long.
[0138] hi some aspects of the compositions comprising cells, wherein the cells comprise a peptide, the fragment of SARS-CoV-2 spike SI comprises all or part of the ACE2-Interacting Domain (ACID) of SARS-CoV-2 spike SI. In some aspects of the compositions comprising cells, wherein the cells comprise a peptide, the fragment of SARS-CoV-2 spike SI comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y. In some aspects of the compositions comprising cells, wherein the cells comprise a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence NGVGY (SEQ ID NO: 7). In some aspects of the compositions comprising cells, wherein the cells comprise a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). In some aspects of the compositions comprising cells, wherein the cells comprise a peptide, the fragment of S ARS-CoV-2 spike S I comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects of the compositions comprising cells, wherein the cells comprise a peptide, the peptide is one or more of the sequences of Table 1. For example, disclosed herein are compositions comprising cells, wherein the cells comprise a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. Disclosed herein are compositions comprising cells, wherein the cells comprise a peptide comprising SEQ ID NO: 11.
[0139] Tn some aspects of the compositions comprising cells, wherein the cells comprise a peptide, the disclosed peptides further comprise a targeting domain. In some aspects of the compositions comprising cells, wherein the cells comprise a peptide, the targeting domain is at the N terminus of the peptide. In some aspects of the compositions comprising cells, wherein the cells comprise a peptide, the targeting domain is at the C terminus of the peptide In some aspects of the compositions comprising cells, wherein the cells comprise a peptide, the targeting domain is ACE2.
[0140] Disclosed are compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0141] In some aspects of the compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the CPP is at the N terminus of the peptide. In some aspects of the compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the CPP is at the C terminus of the peptide.
[0142] In some aspects of the compositions comprising cells, wherein the cells comprisenucleic acid molecules capable of encoding a peptide, the CPP is cationic. In some aspects of the compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the CPP is non-amphipathic.
[0143] In some aspects of the compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the CPP is the cell-penetrating domain of HIV- 1 Tat. In some aspects of the composi tions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: 1). In some aspects of the compositions compri sing cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the CPP is antennapedia homeodomain DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
[0144] In some aspects of the compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI is from about 10 to 20 amino acids long.
[0145] In some aspects of the compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to about 18 amino acids long. In some aspects of the compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to about 15 amino acids long.
[0146] In some aspects of the compositions comprising cells, the cells comprise nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises all or part of tire ACE2-Interacting Domain (ACID) of SARS-CoV-2 spike SI. In some aspects of the compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y. In some aspects of the compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence NGVGY (SEQ ID NO: 7). In some aspects of the compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). In some aspectsof the compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike S I comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects of the compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the peptide is one or more of the sequences of Table 1. For example, disclosed herein are compositions comprising cells, wherein the cells comprise a nucleic acid molecule capable of encoding a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. Disclosed herein are compositions comprising cells, wherein the cells comprise a nucleic acid molecule capable of encoding a peptide comprising SEQ ID NO: 11,
[0147] In some aspects of the compositions comprising cells, the cells comprise nucleic acid molecules capable of encoding a peptide, the disclosed peptides further comprise a targeting domain. In some aspects of the compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, tire targeting domain is at the N terminus of the peptide. In some aspects of the compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the targeting domain is at the C terminus of the peptide. In some aspects of the compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the targeting domain is ACE2.7. Pharmaceutical Compositions
[0148] Disclosed are pharmaceutical compositions comprising any of the peptides, nucleic acid molecules, vectors, cells and compositions disclosed herein and a pharmaceutically acceptable carrier.
[0149] For example, disclosed are pharmaceutical compositions comprising a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0150] Tn some aspects of the pharmaceutical compositions comprising a peptide, the CPP is at the N terminus of the peptide. In some aspects of the pharmaceutical compositions comprising a peptide, the CPP is at the C terminus of the peptide.
[0151] In some aspects of the pharmaceutical compositions comprising a peptide, the CPP is cationic. In some aspects of the pharmaceutical compositions comprising a peptide, the CPP is non-amphipathic.
[0152] In some aspects of the pharmaceutical compositions comprising a peptide, the CPP is the cell -penetrating domain of HIV-1 Tat. In some aspects of the pharmaceutical compositions comprising a peptide, the CPP comprises the amino acid sequenceYARAAARQARA (SEQ ID MO: 1). In some aspects of the pharmaceutical compositions comprising a peptide, the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the pharmaceutical compositions comprising a peptide, the CPP is antennapedia homeodomain DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
[0153] In some aspects of the pharmaceutical compositions comprising a peptide, the fragment of SARS-CoV-2 spike SI is from about 10 to 20 amino acids long.
[0154] In some aspects of the pharmaceutical compositions comprising a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to about 18 ammo acids long. Tn some aspects of the pharmaceutical compositions comprising a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to about 15 amino acids long.
[0155] Tn some aspects of the pharmaceutical compositions comprising a peptide, the fragment of SARS-CoV-2 spike S 1 comprises all or part of the ACE2 -Interacting Domain (ACID) of SARS-CoV-2 spike SI. In some aspects of the pharmaceutical compositions comprising a peptide, the fragment of SARS-CoV-2 spike SI comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y. In some aspects of the pharmaceutical compositions comprising a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence NGVGY (SEQ ID NO: 7). In some aspects of the pharmaceutical compositions comprising a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). In some aspects of the pharmaceutical compositions comprising a peptide, the fragment of SARS-CoV-2 spike S I comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects of the pharmaceutical compositions comprising a peptide, the peptide is one or more of the sequences of Table 1. For example, disclosed herein are pharmaceutical compositions comprising a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12, Disclosed herein are pharmaceutical compositions comprising a peptide comprising SEQ ID NO: 11.
[0156] hi some aspects of the pharmaceutical compositions comprising a peptide, the disclosed peptides further comprise a targeting domain. In some aspects of the pharmaceutical compositions comprising a peptide, the targeting domain is at the N terminus of the peptide. In some aspects of the pharmaceutical compositions comprising a peptide, the targeting domain is at the C terminus of the peptide, hi some aspects of the pharmaceutical composi tions comprising a peptide, the targe ting domain is ACE2.
[0157] Disclosed are pharmaceutical compositions comprising nucleic acid moleculescapable of encoding a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide,
[0158] In some aspects of the pharmaceutical compositions comprising nucleic acid molecules capable of encoding a peptide, the CPP is at the N terminus of the peptide. In some aspects of the pharmaceutical compositions comprising nucleic acid molecules capable of encoding a peptide, the CPP is at the C terminus of the peptide.
[0159] In some aspects of the pharmaceutical compositions comprising nucleic acid molecules capable of encoding a peptide, the CPP is cationic, hi some aspects of the pharmaceutical compositions comprising nucleic acid molecules capable of encoding a peptide, the CPP is non-amphipathic.
[0160] In some aspects of the pharmaceutical compositions comprising nucleic acid molecules capable of encoding a peptide, the CPP is the cell -penetrating domain of HIV-1 Tat. In some aspects of the pharmaceutical compositions comprising nucleic acid molecules capable of encoding a peptide, the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID MO: 1). In some aspects of the pharmaceutical compositions comprising nucleic acid molecules capable of encoding a peptide, the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the pharmaceutical compositions comprising nucleic acid molecules capable of encoding a peptide, the CPP is antennapedia homeodomain DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
[0161] hi some aspects of the pharmaceutical compositions comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI is from about 10 to 20 amino acids long.
[0162] In some aspects of the pharmaceutical compositions comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to about 18 amino acids long. In some aspects of the pharmaceutical compositions comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to about 15 amino acids long.
[0163] In some aspects of the pharmaceutical compositions comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises all or part of the ACE2 -Interacting Domain (ACID) of SARS-CoV-2 spike SI. In some aspects of the pharmaceutical compositions comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined aminoacids S, N and Y. In some aspects of the pharmaceutical compositions comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence NGVGY (SEQ ID NO: 7). In some aspects of the pharmaceutical compositions comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). In some aspects of the pharmaceutical compositions comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects of the pharmaceutical compositions comprising nucleic acid molecules capable of encoding a peptide, the peptide is one or more of the sequences of Table 1. For example, disclosed herein are pharmaceutical compositions comprising nucleic acid molecules capable of encoding a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. Disclosed herein are pharmaceutical compositions comprising nucleic acid molecules capable of encoding a peptide comprising SEQ ID NO: 11.
[0164] hi some aspects of the pharmaceutical compositions comprising nucleic acid molecules capable of encoding a peptide, the disclosed peptides further comprise a targeting domain. In some aspects of the pharmaceutical compositions comprising nucleic acid molecules capable of encoding a peptide, the targeting domain is at the N terminus of the peptide. In some aspects of the pharmaceutical compositions comprising nucleic acid molecules capable of encoding a peptide, the targeting domain is at the C terminus of the peptide. In some aspects of the pharmaceutical compositions comprising nucleic acid molecules capable of encoding a peptide, the targeting domain is ACE2,
[0165] Disclosed are pharmaceutical compositions comprising vectors, wherein the vectors comprise a nucleic acid molecule capable of encoding any of the peptides disclosed herein.
[0166] For example, disclosed are pharmaceutical compositions comprising vectors, wherein the vectors comprise a nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0167] In some aspects of the pharmaceutical compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP is at the N terminus of the peptide, hi some aspects of the pharmaceutical compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP is at the C terminus of the peptide.
[0168] hi some aspects of the pharmaceutical compositions comprising a vector, wherein the vector compri ses a nucleic acid molecule capable of encoding a peptide, the CPP is cationic. In some aspects of the pharmaceutical compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP is non-aniphipathic,
[0169] In some aspects of the pharmaceutical compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP is the cell-penetrating domain of HIV-1 Tat. In some aspects of the pharmaceutical compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: 1).
[0170] In some aspects of the pharmaceutical compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the pharmaceutical compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP is antennapedia homeodomain DRQIK1WFQNRRMKWKK (SEQ ID NO: 4).
[0171] In some aspects of the pharmaceutical compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI is about 10 to about 20 amino acids long. In some aspects of the pharmaceutical compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI is about 12 to about 20 amino acids long.
[0172] In some aspects of the pharmaceutical compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises all or part of the ACE2 -Interacting Domain (ACID) of SARS-CoV-2 spike SI.
[0173] In some aspects of the pharmaceutical compositions comprising a vector, wherein the vector compri ses a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises at least 70°4> identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y. In some aspects of the pharmaceutical compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence NGVGY (SEQ ID NO: 7). In some aspects of thepharmaceutical compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5), In some aspects of the pharmaceutical compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the fragment of S ARS-CoV -2 spike S 1 comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects of the pharmaceutical compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the peptide is one or more of the sequences of Table 1, For example, disclosed herein are pharmaceutical compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. Disclosed herein are pharmaceutical compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide comprising SEQ ID NO: 11.
[0174] hi some aspects of the pharmaceutical compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the peptide further comprises a targeting domain, in some aspects of the pharmaceutical compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the targeting domain is at the N terminus of the peptide. In some aspects of the pharmaceutical compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the targeting domain is at the C terminus of the peptide. In some aspects of the pharmaceutical compositions comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the targeting domain is ACE2.
[0175] Disclosed are pharmaceutical compositions comprising cells, wherein the cells comprise a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0176] hi some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise a peptide, the CPP is at the N terminus of the peptide. In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise a peptide, the CPP is at the C terminus of the peptide.
[0177] In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise a peptide, the CPP is cationic. In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise a peptide, the CPP is non-amphipathic.
[0178] In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise a peptide, the CPP is the cell -penetrating domain of HIV- 1 Tat. In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise a peptide, the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: 1). In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise a peptide, the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise a peptide, the CPP is antennapedia homeodomain DRQIK1WFQNRRMKWKK (SEQ ID NO: 4).
[0179] In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise a peptide, the fragment of SARS-CoV-2 spike SI is from about 10 to 20 amino acids long.
[0180] In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to about 18 amino acids long. In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to about 15 amino acids long.
[0181] In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise a peptide, the fragment of SARS-CoV-2 spike SI comprises all or part of the ACE2-Interacting Domain (ACID) of SARS-CoV-2 spike SI. In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise a peptide, the fragment of SARS-CoV-2 spike SI comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y. In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise a peptide, the fragment of S ARS-CoV-2 spike S I comprises the amino acid sequence NGVGY (SEQ ID NO: 7). In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise a peptide, the fragment of SARS-CoV-2 spike SI comprises the ammo acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise a peptide, the fragment of SARS-CoV -2 spike S 1 comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise a peptide, the peptide is one or more of the sequences of Table 1. For example, disclosed herein are pharmaceutical compositionscomprising cells, wherein the cells comprise a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. Disclosed herein are pharmaceutical compositions comprising cells, wherein the cells comprise a peptide comprising SEQ ID NO: 11.
[0182] In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise a peptide, the disclosed peptides further comprise a targeting domain. In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise a peptide, the targeting domain is at the N terminus of the peptide. In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise a peptide, the targeting domain is at the C terminus of the peptide. In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise a peptide, the targeting domain is ACE2.
[0183] Disclosed are pharmaceutical compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0184] In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the CPP is at the N terminus of the peptide. In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the CPP is at the C terminus of the peptide.
[0185] In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the CPP is cationic. In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the CPP is non-amphipathic.
[0186] In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the CPP is the cellpenetrating domain of HIV-1 Tat. In some aspects of the pharmaceutical compositions compri sing cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the CPP comprises tire amino acid sequence YARAAARQARA (SEQ ID NO: I). In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise nucleic acidmolecules capable of encoding a peptide, the CPP is antennapedia homeodomain DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
[0187] In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI is from about 10 to 20 ammo acids long.
[0188] In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to about 18 amino acids long. In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to about 15 amino acids long.
[0189] Tn some aspects of the pharmaceutical compositions comprising cells, the cells comprise nucleic acid molecules capable of encoding a peptide, tire fragment of SARS-CoV-2 spike SI comprises all or part of the ACE2-Interacting Domain (ACID) of SARS-CoV-2 spike S 1. In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y. In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence NGVGY (SEQ ID NO: 7). hi some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the fragment of S ARS-CoV-2 spike S I comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the peptide is one or more of the sequences of Table 1. For example, disclosed herein are pharmaceutical compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. Disclosed herein are pharmaceutical compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide comprising SEQ ID NO: 11.
[0190] hi some aspects of the pharmaceutical compositions comprising cells, the cells comprise nucleic acid molecules capable of encoding a peptide, the disclosed peptides further comprise a targeting domain. In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the targeting domain is at the N terminus of the peptide. In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the targeting domain is at the C te minus of the peptide. In some aspects of the pharmaceutical compositions comprising cells, wherein the cells comprise nucleic acid molecules capable of encoding a peptide, the targeting domain is ACE2,
[0191] By '‘pharmaceutically acceptable” is meant a material or carrier that would be selected to minimize any degradation of the active ingredient and to minimize any adverse side effects in the subject, as would be well known to one of skill in the art. Examples of carriers include dimyristoylphosphatidyl (DMPC), phosphate buffered saline or a multivesicular liposome. For example, PG: PC: Cholesterol:peptide or PGpeptide can be used as carriers in this invention. Other suitable pharmaceutically acceptable carriers and their formulations are described in Remington: The Science and Practice of Pharmacy (19th ed.) ed. A. R. Gennaro, Mack Publishing Company, Easton, PA 1995. Typically, an appropriate amount of pharmaceutically -acceptable salt is used in the formulation to render the formulation isotonic. Other examples of the pharmaceutically-acceptable carrier include, but are not limited to, saline, Ringer’s solution and dextrose solution. The pH of tire solution can be from about 5 to about 8, or from about 7 to about 7.5. Further carriers include sustained release preparations such as semi-permeable matrices of solid hydrophobic polymers containing the composition, which matrices are in the form of shaped articles, e.g., films, stents (which are implanted in vessels during an angioplasty procedure), liposomes or microparticles. It will be apparent to those persons skilled in the art that certain carriers may be more preferable depending upon, for instance, the route of administration and concentration of composition being administered. These most typically would be standard carriers for administration of drags to humans, including solutions such as sterile water, saline, and buffered solutions at physiological pH.
[0192] Pharmaceutical compositions can also include carriers, thickeners, diluents, buffers, preservatives and the like, as long as the intended activity of the polypeptide, peptide, nucleic acid, vector of the invention is not compromised. Pharmaceutical compositions may also include one or more active ingredients (in addition to the composition of the invention) such as antimicrobial agents, anti-inflammatory agents, anesthetics, and the like. Thepharmaceutical composition may be administered in a number of ways depending on whether local or systemic treatment is desired, and on the area to be treated.
[0193] Preparations of parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions. Examples of non-aqueous solvents are propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate. Aqueous carriers include water, alcoholic / aqueous solutions, emulsions or suspensions, including saline and buffered media. Parenteral vehicles include sodium chloride solution, Ringer’s dextrose, dextrose and sodium chloride, lactated Ringer’s, or fixed oils. Intravenous vehicles include fluid and nutrient replenishers, electrolyte replenishers (such as those based on Ringer’s dextrose), and the like. Preservatives and other additives may also be present such as, for example, antimicrobials, anti-oxidants, chelating agents, and inert gases and the like,
[0194] Formulations for optical administration may include ointments, lotions, creams, gels, drops, suppositories, sprays, liquids and powders. Conventional pharmaceutical carriers, aqueous, powder or oily bases, thickeners and the like may be necessary or desirable.
[0195] Compositions for oral administration include powders or granules, suspensions or solutions in water or non-aqueous media, capsules, sachets, or tablets. Thickeners, flavorings, diluents, emulsifiers, dispersing aids, or binders may be desirable. Some of the compositions may potentially be administered as a pharmaceutically acceptable acid- or baseaddition salt, formed by reaction with inorganic acids such as hydrochloric acid, hydrobromic acid, perchloric acid, nitric acid, thiocyanic acid, sulfuric acid, and phosphoric acid, and organic acids such as formic acid, acetic acid, propionic acid, glycolic acid, lactic acid, pyruvic acid, oxalic acid, malonic acid, succinic acid, maleic acid, and fumaric acid, or by reaction with an inorganic base such as sodium hydroxide, ammonium hydroxide, potassium hydroxide, and organic bases such as mon-, di-, trialkyl and aryl amines and substituted ethanolamines.C. Methods1. Methods For Treating Cancer
[0196] Disclosed herein are methods of treating cancer in a subject in need thereof comprising administering any one of the disclosed peptides, nucleic acids, vectors, cells, compositions or pharmaceutical compositions to the subject.
[0197] Disclosed herein are methods of treating cancer in a subject in need thereof comprising administering an effective amount of a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0198] hi some aspects of the methods of treating cancer, the CPP is at the N terminus of tiie peptide. In some aspects of the methods of treating cancer, the CPP is at the C terminus of the peptide.
[0199] In some aspects of the methods of treating cancer, the CPP is cationic. In some aspects of the methods of treating cancer, the CPP is non-amphipathic.
[0200] In some aspects of the methods of treating cancer, the CPP is the cell -penetrating domain of HIV- 1 Tat. hi some aspects of the methods of treating cancer, the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: 1). In some aspects of the methods of treating cancer, the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the methods of treating cancer, the CPP is antennapedia homeodomain DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
[0201] In some aspects of the methods of treating cancer, the fragment of SARS-CoV-2 spike SI is from about 10 to 20 amino acids long.
[0202] In some aspects of the methods of treating cancer, the fragment of SARS-CoV-2 spike SI is from 12 to 18 amino acids long, hi some aspects of the methods of treating cancer, the fragment of SARS-CoV-2 spike SI is from about 12 to 15 amino acids long.
[0203] In some aspects of the methods of treating cancer, the fragment of SARS-CoV-2 spike SI is 10 amino acids long. In some aspects of the methods of treating cancer, the fragment of SARS-CoV-2 spike S 1 is 11 amino acids long. In some aspects of the methods of treating cancer, the fragment of SARS-CoV-2 spike SI is 12 amino acids long. In some aspects of the methods of treating cancer, the fragment of SARS-CoV-2 spike SI is 13 amino acids long. In some aspects of the methods of treating cancer, the fragment of SARS-CoV-2 spike SI is 14 amino acids long. In some aspects of the methods of treating cancer, the fragment of SARS-CoV-2 spike SI is 15 amino acids long. In some aspects of the methods of treating cancer, the fragment of SARS-CoV-2 spike SI is 16 amino acids long. In some aspects of the methods of treating cancer, the fragment of SARS-CoV-2 spike S 1 is 17 ammo acids long. In some aspects of the methods of treating cancer, the fragment of SARS-CoV-2 spike SI is 18 amino acids long. In some aspects of the methods of treating cancer, the fragment of SARS-CoV-2 spike SI is 19 amino acids long. In some aspects of the methods of treating cancer, the fragment of SARS-CoV-2 spike SI is 20 amino acids long.
[0204] In some aspects of the methods of treating cancer, the fragment of SARS-CoV-2 spike S I comprises all or part of the ACE2-Interacting Domain (ACID) of SARS-CoV-2 spike S 1. In some aspects of the methods of treating cancer, the fragment of SARS-CoV-2 spike SI comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEO ID NO:5) and comprises the underlined amino acids S, N and Y In some aspects of the methods of treating cancer, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence NGVGY (SEQ ID NO: 7). In some aspects of the methods of treating cancer, the fragment of SARS-CoV-2 spike Si comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). In some aspects of the methods of treating cancer, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects of the methods of treating cancer, the peptide is one or more of the sequences of Table 1. For example, disclosed herein are methods of treating cancer with a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12, Disclosed herein are methods of treating cancer with a peptide comprising SEQ ID NO: 11.
[0205] In some aspects of the methods of treating cancer, the disclosed peptides can be made synthetically or recombinantly.
[0206] In some aspects of the methods of treating cancer, the disclosed peptides further comprise a targeting domain. In some aspects of the methods of treating cancer, the targeting domain is at the N terminus of tire peptide. In some aspects of the methods of treating cancer, the targeting domain is at the C terminus of the peptide. In some aspects of the methods of treating cancer, the targeting domain is ACE2.
[0207] Disclosed herein are methods of treating cancer in a subject in need thereof comprising administering an effective amount of a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0208] In some aspects of the methods of treating cancer, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the CPP is at the N terminus of the peptide. In some aspects of the methods of treating cancer, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike S 1 peptide, wherein the CPP is at the C terminus of the peptide.
[0209] hi some aspects of the methods of treating cancer, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the CPP is cationic. In some aspects of the methods of treating cancer, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the CPP is non-amphipathic.
[0210] In some aspects of the methods of treating cancer, the nucleic acid moleculeencodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of tire SARS-CoV-2 spike S I peptide, wherein the CPP is the cell-penetrating domain ofHIV-1 Tat, In some aspects of the methods of treating cancer, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: I), In some aspects of the methods of treating cancer, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the methods of treating cancer, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the CPP is antennapediahomeodomain DRQIKTWFQNRRMKWKK (SEQ ID NO: 4).
[0211] In some aspects of the methods of treating cancer, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the fragment of SARS-CoV-2 spike SI is about 10-20 amino acids long. In some aspects of the methods of treating cancer, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the fragment of SARS-CoV-2 spike SI is about 12-15 amino acids long.
[0212] In some aspects of the methods of treating cancer, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of tire SARS-CoV-2 spike SI peptide, wherein the fragment of SARS-CoV-2 spike SI comprises all or part of the ACE2-Interacting Domain (ACID) of SARS-CoV-2 spike SI. In some aspects of the methods of treating cancer, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5).
[0213] In some aspects of the methods of treating cancer, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the fragment of SARS-CoV-2 spike SI comprises all or part of the ACE2-Interacting Domain (ACID) of SARS-CoV-2 spike SI. In some aspects of the methods of treating cancer, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the fragment of SARS-CoV-2 spike SI comprises at least 70% identity to thesequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S. N and Y. In some aspects of the methods of treating cancer, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence NGVGY (SEQ ID NO: 7). In some aspects of the methods of treating cancer, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the fragment of SARS-CoV-2 spike SI comprises tire amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5), In some aspects of the methods of treating cancer, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects of the methods of treating cancer, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the peptide is one or more of the sequences of Table 1. For example, disclosed herein are methods of treating cancer with a nucleic acid molecule encoding a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. Disclosed herein are methods of treating cancer with a nucleic acid molecule encoding a peptide comprising SEQ ID NO: 11.
[0214] In some aspects of the methods of treating cancer, the nucleic acid molecule encodes a peptide further comprising a targeting domain. In some aspects of the methods of treating cancer, the nucleic acid molecule encodes a peptide wherein the targeting domain is at the N terminus of the peptide. In some aspects of the methods of treating cancer, the nucleic acid molecule encodes a peptide wherein the targeting domain is at the C terminus of the peptide. In some aspects of the methods of treating cancer, the nucleic acid molecule encodes a peptide further comprising a targeting domain, wherein the targeting domain is ACE2.
[0215] Disclosed herein are methods of treating cancer in a subject in need thereof comprising administering an effecti ve amount of a vector comprising a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0216] In some aspects of the methods of treating cancer, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the CPP is at the N terminus of the peptide. In some aspects of the methods of treating cancer, the vectors comprise a nucleicacid molecule capable of encoding a peptide wherein the CPP is at the C terminus of the peptide.
[0217] In some aspects of the methods of treating cancer, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the CPP is cationic. In some aspects of the methods of treating cancer, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the CPP is non-amphipathic.
[0218] In some aspects of the methods of treating cancer, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the CPP is tire cell-penetrating domain of HIV-1 Tat. In some aspects of the methods of treating cancer, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: 1).
[0219] In some aspects of the methods of treating cancer, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the methods of treating cancer, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the CPP is antennapedia homeodomain DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
[0220] In some aspects of the methods of treating cancer, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the fragment of SARS-CoV-2 spike SI is about 10 to about 20 amino acids long. In some aspects of the methods of treating cancer, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the fragment of SARS-CoV-2 spike SI is about 12 to about 20 amino acids long,
[0221] In some aspects of the methods of treating cancer, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the fragment of SARS-CoV-2 spike SI comprises all or part of tire ACE2-Interacting Domain (ACID) of SARS-CoV-2 spike SI.
[0222] In some aspects of the methods of treating cancer, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the fragment of SARS-CoV-2 spike SI comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y. In some aspects of the methods of treating cancer, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence NGVGY (SEQ ID NO: 7). In some aspects of the methods of treating cancer, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). In some aspectsof the methods of treating cancer, the vectors comprise a nucleic acid molecule capable of encoding a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects of the methods of treating cancer, the nucleic acid molecule encodes a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide, wherein the peptide is one or more of the sequences of Table 1. For example, disclosed herein are methods of treating cancer with a nucleic acid molecule encoding a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. Disclosed herein are methods of treating cancer with a nucleic acid molecule encoding a peptide comprising SEQ ID NO: II.
[0223] In some aspects of the methods of treating can cer, the vectors comprise a nucleic acid molecule capable of encoding a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide and further comprising a targeting domain. In some aspects of the methods of treating cancer, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the targeting domain is at the N terminus of the peptide. In some aspects of the methods of treating cancer, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the targeting domain is at the C terminus of the peptide. In some aspects of the methods of treating cancer, the vectors comprise a nucleic acid molecule capable of encoding a peptide wherein the targeting domain is ACE2.
[0224] Disclosed are methods of treating cancer in a subject in need thereof comprising administering an effective amount of a cell comprising a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0225] In some aspects of the methods of treating can cer comprising administeri ng an effective amount of a cell comprising a peptide, the CPP is at the N terminus of the peptide. In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising a peptide, the CPP is at the C terminus of the peptide.
[0226] In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising a peptide, the CPP is cationic. In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising a peptide, the CPP is non-amphipathic.
[0227] In some aspects of the methods of treating cancer comprising administering aneffective amount of a cell comprising a peptide, the CPP is the cell-penetrating domain of HIV-1 Tat. In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising a peptide, the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: 1). In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising a peptide, the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising a peptide, the CPP is antennapedia homeodomain DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
[0228] In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising a peptide, the fragment of SARS-CoV-2 spike SI is from about 10 to 20 amino acids long.
[0229] In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising a peptide, the fragment of SARS-CoV-2 spike SI is from 12 to 18 amino acids long. In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to 15 amino acids long.
[0230] In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising a peptide, the fragment of SARS-CoV-2 spike S I comprises all or part of the ACE2-Interacting Domain (ACID) of SARS-CoV-2 spike SI. In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising a peptide, the fragment of S ARS-CoV-2 spike S I comprises at least 70% identity to the sequence OSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y. hi some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence NGVGY (SEQ ID NO: 7). In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects of the methods of treating cancer comprising adminis tering an effective amount of a cell comprising a peptide, the peptide is one or more of the sequences of Table 1. For example, disclosed herein are methods oftreating cancer comprising administering an effective amount of a cell comprising a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12, Disclosed herein are methods of treating cancer comprising administering an effective amoun t of a cell comprising a peptide comprising SEQ ID NO: 11.
[0231] In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising a peptide, the disclosed peptides further comprise a targeting domain. In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising a peptide, the targeting domain is at the N terminus of the peptide. In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising a peptide, the targeting domain is at the C terminus of the peptide. In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising a peptide, the targeting domain is ACE2.
[0232] Disclosed are methods of treating cancer in a subject in need thereof comprising administering an effective amount of a cell comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0233] In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising nucleic acid molecules capable of encoding a peptide, the CPP is at the N terminus of the peptide. In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising nucleic acid molecules capable of encoding a peptide, the CPP is at tire C terminus of tire peptide.
[0234] In some aspects of the methods of treating cancer comprising administering an effective amoun t of a cell comprising nucleic acid molecules capable of encoding a pep tide, the CPP is cationic. In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising nucleic acid molecules capable of encoding a peptide, the CPP is non-amphipathic.
[0235] In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising nucleic acid molecules capable of encoding a peptide, the CPP is the cell -penetrating domain of HIV-1 Tat. In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising nucleic acid molecules capable of encoding a peptide, the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: 1). In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising nucleic acid molecules capable of encoding a peptide, the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) orRRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising nucleic acid molecules capable of encoding a peptide, the CPP is antennapedia homeodomain DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
[0236] Tn some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI is from about 10 to 20 amino acids long.
[0237] hi some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI is from 12 to 18 amino acids long. In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to 15 amino acids long.
[0238] In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises all or part of the ACE2 -Interacting Domain (ACID) of SARS-CoV-2 spike SI. In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising nucleic acid molecules capable of encoding a peptide, the fragment of S ARS-CoV-2 spike S I comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y. In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises tire amino acid sequence NGVGY (SEQ ID NO: 7). In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising nucleic acid molecules capable of encoding a peptide, the fragment of S ARS-CoV-2 spike S I comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising nucleic acid molecules capable of encoding a pepti de, the fragment of S ARS-CoV-2 spike S I comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising nucleic acid molecules capable of encoding a peptide, tire peptide is one or more of the sequences of Table 1. For example, disclosed herein are methods of treating cancer comprising administering an effective amount of a cell comprising nucleic acid moleculescapable of encoding a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12, Disclosed herein are methods of treating cancer comprising administering an effective amount of a cell comprising nucleic acid molecules capable of encoding a peptide comprising SEQ ID NO: 11.
[0239] Tn some aspects of the methods of treating can cer comprising administering an effective amount of a cell comprising nucleic acid molecules capable of encoding a peptide, the disclosed peptides further comprise a targeting domain. In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising nucleic acid molecules capable of encoding a peptide, the targeting domain is at the N terminus of the peptide. In some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising nucleic acid molecules capable of encoding a peptide, the targeting domain is at the C terminus of the peptide. Tn some aspects of the methods of treating cancer comprising administering an effective amount of a cell comprising nucleic acid molecules capable of encoding a peptide, the targeting domain is ACE2.
[0240] Disclosed herein are methods of treating cancer comprising administering a composition comprising the peptides, nucleic acid constructs, vectors and cells disclosed herein.
[0241] For example, disclosed are methods of treating cancer comprising administering a composition comprising a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0242] hi some aspects of the methods of treating cancer comprising administering a composition comprising a peptide, the CPP is at the N terminus of the peptide. In some aspects of the methods of treating cancer comprising adminis tering a composi tion comprising a peptide, the CPP is at the C terminus of the peptide.
[0243] In some aspects of the methods of treating cancer comprising administering a composition comprising a peptide, the CPP is cationic. In some aspects of the methods of treating cancer comprising administering a composition comprising a peptide, the CPP is non-amphipathic.
[0244] In some aspects of the methods of treating cancer comprising administering a composition comprising a peptide, the CPP is the cell-penetrating domain of HIV-1 Tat. In some aspects of the methods of treating cancer comprising administering a composition comprising a peptide, the CPP comprises die amino acid sequence YARAAARQARA (SEQ ID NO: 1). In some aspects of the methods of treating cancer comprising administering a composition comprising a peptide, the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2)or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the methods of treating cancer comprising administering a composition comprising a peptide, the CPP is antennapedia homeodomain DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
[0245] In some aspects of the methods of treating cancer comprising administering a composition comprising a peptide, the fragment of SARS-CoV-2 spike SI is from about 10 to 20 amino acids long.
[0246] In some aspects of the methods of treating cancer comprising administering a composition comprising a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to about 18 amino acids long. In some aspects of the methods of treating cancer comprising administering a composition comprising a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to about 15 amino acids long.
[0247] Tn some aspects of the methods of treating cancer comprising administering a composition comprising a peptide, the fragment of SARS-CoV-2 spike SI comprises all or part of the ACE2-Interacting Domain (ACID) of SARS-CoV-2 spike S 1. In some aspects of the methods of treating cancer comprising administering a composition comprising a peptide, the fragment of SARS-CoV-2 spike SI comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y. In some aspects of the methods of treating cancer comprising administering a composition comprising a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence NGVGY (SEQ ID NO: 7). In some aspects of the methods of treating cancer comprising administering a composition comprising a peptide, the fragment of SARS-Co V -2 spike SI comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). In some aspects of the methods of treating cancer comprising administering a composition comprising a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects of the methods of treating cancer comprising administering a composition comprising a peptide, the peptide is one or more of the sequences of Table 1. For example, disclosed herein are methods of treating cancer comprising administering a composition comprising a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. Disclosed herein are methods of treating cancer comprising administering a composition comprising a peptide comprising SEQ ID NO: 11.
[0248] In some aspects of the methods of treating cancer comprising administering a composition comprising a peptide, the disclosed peptides further comprise a targeting domain. In some aspects of the methods of treating cancer comprising administering acomposition comprising a peptide, the targeting domain is at the N tenninus of the peptide. In some aspects of the methods of treating cancer comprising administering a composition comprising a peptide, the targeting domain is at the C terminus of the peptide. In some aspects of the methods of treating cancer comprising administering a composition comprising a peptide, the targeting domain is ACE2.
[0249] Disclosed are methods of treating cancer comprising administering a compositions comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0250] In some aspects of the methods of treating cancer comprising administering a composition comprising nucleic acid molecules capable of encoding a peptide, the CPP is at the N terminus of the peptide. In some aspects of the methods of treating cancer comprising administering a composition comprising nucleic acid molecules capable of encoding a peptide, the CPP is at the C tenninus of the peptide.
[0251] hi some aspects of the methods of treating cancer comprising administering a composition comprising nucleic acid molecules capable of encoding a peptide, the CPP is cationic. In some aspects of the methods of treating cancer comprising administering a composition comprising nucleic acid molecules capable of encoding a peptide, the CPP is non-amphipath ic.
[0252] In some aspects of the methods of treating cancer comprising administering a composition comprising nucleic acid molecules capable of encoding a peptide, the CPP is the cell -penetrating domain of HIV- 1 Tat. In some aspects of the methods of treating cancer comprising administering a composition comprising nucleic acid molecules capable of encoding a peptide, the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: 1). In some aspects of the methods of treating cancer comprising administering a composition comprising nucleic acid molecules capable of encoding a peptide, the CPP is polyargmine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). in some aspects of the methods of treating cancer comprising administering a composition comprising nucleic acid molecules capable of encoding a peptide, the CPP is antennapedia homeodomain DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
[0253] In some aspects of the methods of treating cancer comprising administering a composition comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI is from about 10 to 20 amino acids long.
[0254] In some aspects of the methods of treating cancer comprising administering acomposition comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to about 18 amino acids long. In some aspects of the methods of treating cancer comprising administering a composition comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to about 15 amino acids long,
[0255] In some aspects of the methods of treating cancer comprising administering a composition comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises all or part of the ACE2-Interacting Domain (ACID) of SARS-CoV-2 spike SI. In some aspects of the methods of treating cancer composing administering a composition comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y. In some aspects of the methods of treating cancer comprising administering a composition comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises tire amino acid sequence NGVGY (SEQ ID NO: 7). In some aspects of the methods of treating cancer comprising administering a composition comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). In some aspects of the methods of treating cancer comprising administering a composition comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects of the methods of treating cancer comprising administering a composition comprising nucleic acid molecules capable of encoding a peptide, the peptide is one or more of the sequences of Table 1. For example, disclosed herein are methods of treating cancer comprising administering a composition comprising nucleic acid molecules capable of encoding a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. Disclosed herein are methods of treating cancer comprising administering a composition comprising nucleic acid molecules capable of encoding a peptide comprising SEQ ID NO: 11.
[0256] In some aspects of the methods of treating cancer comprising administering a composition comprising nucleic acid molecules capable of encoding a peptide, the disclosed peptide further comprises a targeting domain. In some aspects of the methods of treating cancer comprising administering a composition comprising nucleic acid molecules capable of encoding a peptide, the targeting domain is at the N terminus of the peptide. In some aspectsof the methods of treating cancer comprising administering a composition comprising nucleic acid molecules capable of encoding a peptide, the targeting domain is at the C terminus of the peptide. In some aspects of the methods of treating cancer comprising administering a composition comprising nucleic acid molecules capable of encoding a peptide, the targeting domain is ACE2.
[0257] Disclosed are methods of treating cancer comprising adminis tering a composi tion comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding any of the peptides disclosed herein.
[0258] For example, disclosed are methods of treating cancer comprising administering a composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0259] In some aspects of the methods of treating cancer comprising administering a composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP is at the N tenninus of the peptide. In some aspects of the methods of treating cancer comprising administering a composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP is at the C terminus of the peptide.
[0260] Tn some aspects of the methods of treating can cer comprising administering a composi tion comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP is cationic. In some aspects of the methods of treating cancer comprising administering a composition composing a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP is non-amphipathic.
[0261] In some aspects of the methods of treating cancer comprising administering a composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP is the cell -penetrating domain of HIV- 1 Tat. In some aspects of the methods of treating cancer comprising administering a composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: 1).
[0262] In some aspects of the methods of treating cancer comprising administering a composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the methods of treating cancercomprising administering a composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP is antennapedia homeodomain DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
[0263] In some aspects of the methods of treating cancer comprising administering a composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI is about 10 to about 20 amino acids long. In some aspects of the methods of treating cancer comprising administering a composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike S I is about 12 to about 20 amino acids long.
[0264] In some aspects of the methods of treating cancer comprising administering a composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises all or part of the ACE2 -Interacting Domain (ACID) of SARS-CoV-2 spike SI.
[0265] hi some aspects of the methods of treating cancer comprising administering a composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y. In some aspects of the methods of treating cancer comprising administering a composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-Co V -2 spike S 1 comprises the ammo acid sequence NGVGY (SEQ ID NO: 7), In some aspects of the methods of treating cancer comprising administering a composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). In some aspects of the methods of treating cancer comprising administering a composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). Tn some aspects of the methods of treating cancer comprising administering a composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the peptide is one or more of the sequences of Table 1. For example, disclosed herein are methods of treating cancer comprising administering a composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide comprising SEQ ID NO: 9,SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. Disclosed herein are methods of treating cancer comprising administering a composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide comprising SEQ ID NO: 11.
[0266] In some aspects of the methods of treating can cer comprising administeri ng a composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the peptide further comprises a targeting domain. In some aspects of the methods of treating cancer comprising administering a composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the targeting domain is at the N terminus of the peptide. In some aspects of the methods of treating cancer comprising administering a composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the targeting domain is at the C terminus of the peptide. In some aspects of the methods of treating cancer comprising administering a composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the targeting domain is ACE2.
[0267] Disclosed are methods of treating cancer in a subject in need thereof comprising administering a composition comprising a cell, wherein tlie cell comprises a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0268] In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a peptide, tlie CPP is at the N terminus of the peptide. In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a peptide, the CPP is at the C terminus of the peptide.
[0269] In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, w'herein the cell comprises a peptide, the CPP is cationic. In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a peptide, the CPP is non-amphipathic.
[0270] In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a peptide, the CPP is the cellpenetrating domain of HIV- 1 Tat. In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein tire cell comprises a peptide, the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: 1). In some aspects of the methods of treating cancer comprising administering a compositioncomprising a cell, wherein the cell comprises a peptide, the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a peptide, the CPP is antennapedia homeodomain DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
[0271] In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a peptide, the fragment of SARS-CoV-2 spike SI is from about 10 to 20 amino acids long.
[0272] In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to about 18 amino acids long. In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a peptide, the fragment of SARS-CoV-2 spike S 1 is from about 12 to about 15 amino acids long.
[0273] In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a peptide, the fragment of SARS-CoV-2 spike SI comprises all or part of the ACE2-Interacting Domain (ACID) of SARS-CoV-2 spike SI. hi some aspects of the methods of treating cancer comprising administering a composition compri sing a cell, wherein the cell compri ses a peptide, the fragment of SARS-CoV-2 spike SI comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y. In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence NGVGY (SEQ ID NO: 7). In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a peptide, the fragment of SARS-CoV-2 spike SI composes the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a peptide, the peptide is one or more of the sequences of Table 1. For example, disclosed herein are methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ IDNO: 11 or SEQ ID NO: 12. Disclosed herein are methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a peptide comprising SEQ ID NO: 11.
[0274] In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a peptide, the peptide further comprises a targeting domain. In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a peptide, the targeting domain is at the N terminus of the peptide. In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a peptide, the targeting domain is at the C terminus of the peptide. In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a peptide, the targeting domain is ACE2,
[0275] Disclosed are methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0276] In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the CPP is at the N terminus of the peptide. In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the CPP is at the C terminus of the peptide,
[0277] In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the CPP is cationic, hr some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the CPP is non-amphipathic.
[0278] hi some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the CPP is the cell -penetrating domain of HIV- 1 Tat. In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: 1). In some aspects of the methods of treating cancer comprising administering a composition comprising a cell,wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the CPP is antennapedia homeodomain DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
[0279] In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike S I is from about 10 to 20 amino acids long.
[0280] In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to about 18 amino acids long. In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to about 15 amino acids long.
[0281] In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike S 1 comprises all or part of the ACE2-Interacting Domain (ACID) of SARS-CoV-2 spike SI. In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the fragment of S ARS-CoV-2 spike SI comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y. In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence NGVGY (SEQ ID NO: 7), In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). hi some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV -2 spikeSI comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the peptide is one or more of the sequences of Table 1. For example, disclosed herein are methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. Disclosed herein are methods of treating cancer comprising administering a composition comprising a cell, wherein the cell composes a nucleic acid molecule capable of encoding a peptide compri sing SEQ ID NO: II.
[0282] In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the peptide further comprises a targeting domain. In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the targeting domain is at the N terminus of the peptide. In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the targeting domain is at the C terminus of the peptide. In some aspects of the methods of treating cancer comprising administering a composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the targeting domain is ACE2.
[0283] Disclosed herein are methods of treating cancer comprising administering a pharmaceutical composition comprising the peptides, nucleic acid constructs, vectors and cells disclosed herein.
[0284] For example, disclosed are methods of treating cancer comprising administering a phar aceutical composition comprising a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0285] hi some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a peptide, the CPP is at the N terminus of the peptide. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a peptide, the CPP is at the C terminus of the peptide.
[0286] In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a peptide, the CPP is cationic. In some aspects of themethods of treating cancer comprising administering a pharmaceutical composition comprising a peptide, the CPP is non-amphipathic.
[0287] In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a peptide, the CPP is the cell-penetrating domain of HIV-1 Tat. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a peptide, the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: 1). In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a peptide, the CPP is polyargmine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a peptide, tire CPP is antennapedia homeodomain DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
[0288] In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a peptide, the fragment of SARS-CoV-2 spike SI is from about 10 to 20 amino acids long.
[0289] In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to about 18 amino acids long. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to about 15 amino acids long.
[0290] hi some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a peptide, the fragment of S ARS-CoV -2 spike S 1 comprises all or part of the ACE2-Interacting Domain (ACID) of SARS-CoV-2 spike SI. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a peptide, the fragment of SARS-CoV-2 spike SI comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence NGVGY (SEQ ID NO: 7), In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequenceQAYGFGPTGGVGD (SEQ ID NO: 6) In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a peptide, the peptide is one or more of the sequences of Table 1. For example, disclosed herein are methods of treating cancer comprising administering a pharmaceutical composition comprising a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. Disclosed herein are methods of treating cancer comprising administering a pharmaceutical composition comprising a peptide comprising SEQ ID NO: 11.
[0291] hi some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a peptide, the disclosed peptides further comprise a targeting domain. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a peptide, the targeting domain is at the N terminus of the peptide. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a peptide, the targeting domain is at the C terminus of the peptide. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a peptide, the targeting domain is ACE2.
[0292] Disclosed are methods of treating cancer comprising administering a pharmaceutical composition comprising nucleic acid molecules capable of encoding a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the S ARS-CoV-2 spike S 1 peptide,
[0293] In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising nucleic acid molecules capable of encoding a peptide, the CPP is at the N terminus of the peptide. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising nucleic acid molecules capable of encoding a peptide, the CPP is at the C terminus of the peptide.
[0294] In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising nucleic acid molecules capable of encoding a peptide, the CPP is cationic. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising nucleic acid molecules capable of encoding a peptide, the CPP is non -amphipathic.
[0295] In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising nucleic acid molecules capable of encoding a peptide, the CPP is the cell -penetrating domain of HIV- 1 Tat. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising nucleic acid molecules capable of encoding a peptide, the CPP comprises the amino acidsequence YARAAARQARA (SEQ ID NO: 1). In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising nucleic acid molecules capable of encoding a peptide, the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising nucleic acid molecules capable of encoding a peptide, the CPP is antennapedia homeodomain DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
[0296] hi some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV -2 spike S 1 is from about 10 to 20 amino acids long.
[0297] In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike S 1 is from about 12 to about 18 amino acids long. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to about 15 amino acids long.
[0298] In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises all or part of the ACE2 -Interacting Domain (ACID) of SARS-CoV-2 spike SI. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y. hr some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence NGVGY (SEQ ID NO: 7). In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises tire amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising nucleic acid molecules capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspectsof the methods of treating cancer comprising administering a pharmaceutical composition comprising nucleic acid molecules capable of encoding a peptide, the peptide is one or more of tire sequences of Table I. For example, disclosed herein are methods of treating cancer comprising administering a pharmaceutical composition comprising nucleic acid molecules capable of encoding a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. Disclosed herein are methods of treating cancer comprising administering a pharmaceutical composition comprising nucleic acid molecules capable of encoding a peptide comprising SEQ ID NO: 11.
[0299] In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising nucleic acid molecules capable of encoding a peptide, the disclosed peptide further comprises a targeting domain, hi some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising nucleic acid molecules capable of encoding a peptide, the targe ting domain is at the N terminus of the peptide, hi some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising nucleic acid molecules capable of encoding a peptide, the targeting domain is at the C terminus of the peptide. In some aspects of the methods of treating cancer comprising administering a pharmace utical composition comprising nucleic acid molecules capable of encoding a peptide, the targeting domain is ACE2.
[0300] Disclosed are methods of treating cancer comprising adminis tering a pharmaceutical composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding any of the peptides disclosed herein.
[0301] For example, disclosed are methods of treating cancer comprising administering a pharmaceutical composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0302] In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a vector, wherein tire vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP is at the N terminus of the peptide. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP is at the C terminus of the peptide.
[0303] In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a vector, wherein tire vector comprises a nucleic acidmolecule capable of encoding a peptide, the CPP is cationic. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP is non-amphipathic.
[0304] Tn some aspects of the methods of treating can cer comprising administeri ng a pharmaceutical composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP is the cell-penetrating domain of HIV-1 Tat. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: 1).
[0305] Tn some aspects of the methods of treating can cer comprising administering a pharmaceutical composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the CPP is antennapedia homeodomam DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
[0306] Tn some aspects of the methods of treating can cer comprising administering a pharmaceutical composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-Co V -2 spike S 1 is about 10 to about 20 amino acids long. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI is about 12 to about 20 amino acids long.
[0307] Tn some aspects of the methods of treating can cer comprising administering a pharmaceutical composition comprising a vector, wherein tire vector comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-Co V -2 spike S 1 comprises all or part of the ACE2-Interacting Domain (ACID) of SARS-CoV-2 spike SI.
[0308] In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV -2 spike S 1 comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y. In some aspects of the methods of treating cancercomprising administering a pharmaceutical composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence NGVGY (SEQ ID NO: 7). In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the peptide is one or more of the sequences of Table 1. For example, disclosed herein are methods of treating cancer comprising administering a pharmaceutical composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. Disclosed herein are methods of treating cancer comprising administering a pharmaceutical composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide comprising SEQ ID NO: 11.
[0309] In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the peptide further comprises a targeting domain. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the targeting domain is at the N terminus of the peptide. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the targeting domain is at the C terminus of the peptide. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a vector, wherein the vector comprises a nucleic acid molecule capable of encoding a peptide, the targeting domain is ACE2.
[0310] Disclosed are methods of treating cancer in a subject in need thereof comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises apeptide, wherein the peptide comprises: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0311] In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, the CPP is at the N terminus of the peptide. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, the CPP is at the C terminus of the peptide.
[0312] In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, the CPP is cationic. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, the CPP is non-amphipathic.
[0313] In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein tlie cell comprises a peptide, the CPP is the cell-penetrating domain of HIV- 1 Tat. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: 1). In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, the CPP is antennapedia homeodomain DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
[0314] In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, the fragment of SARS-CoV-2 spike SI is from about 10 to 20 amino acids long,
[0315] In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein tire cell comprises a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to about 18 ammo acids long. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to about 15 amino acids long.
[0316] In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein tire cell comprises a peptide, thefragment of SARS-CoV-2 spike S 1 comprises all or part of the ACE2 -Interacting Domain (ACID) of SARS-CoV-2 spike SI, In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a celt wherein the cell comprises a peptide, the fragment of SARS-CoV-2 spike SI comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y, In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence NGVGY (SEQ ID NO: 7), In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5), In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6) In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, the peptide is one or more of the sequences of Table 1. For example, disclosed herein are methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. Disclosed herein are methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide comprising SEQ ID NO: 11,
[0317] In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, the peptide further comprises a targeting domain. In some aspects of the methods of treating cancer composing administering a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, the targeting domain is at the N terminus of the peptide. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, the targeting domain is at the C terminus of the peptide. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a peptide, the targeting domain is ACE2
[0318] Disclosed are methods of treating cancer comprising adminis tering a pharmaceutical composition comprising a cell, wherein tire cell comprises a nucleic acidmolecule capable of encoding a peptide, wherein the peptide comprises: a) a ceil penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0319] In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the ceil comprises a nucleic acid molecule capable of encoding a peptide, the CPP is at the N terminus of the peptide. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the CPP is at the C terminus of tire peptide.
[0320] In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the CPP is cationic. In some aspects of the methods of treating cancer composing administering a pharmaceutical composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the CPP is non-amphipathic.
[0321] hi some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the CPP is the cell-penetrating domain of HIV-1 Tat. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: 1). In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). in some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the CPP is antennapedia homeodomain DRQIK1WFQNRRMKWKK (SEQ ID NO: 4).
[0322] hi some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike S 1 is from about 10 to 20 amino acids long.
[0323] In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike S 1 is from about12 to about 18 amino acids long. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition composing a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI is from about 12 to about 15 amino acids long.
[0324] Tn some aspects of the methods of treating cancer comprising administeri ng a pharmaceutical composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike S 1 comprises all or part of the ACE2-Interacting Domain (ACID) of SARS-CoV-2 spike SI. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein tire cell comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-Co V -2 spike S 1 comprises the amino acid sequence NGVGY (SEQ ID NO: 7). In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the ceil comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the fragment of SARS-CoV-2 spike S 1 compri ses the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the peptide is one or more of the sequences of Table 1. For example, disclosed herein are methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. Disclosed herein are methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide comprising SEQ ID NO: 11.
[0325] In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein tire cell comprises a nucleic acidmolecule capable of encoding a peptide, the peptide further comprises a targeting domain. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the targeting domain is at the N terminus of the peptide. In some aspects of the methods of treating cancer comprising administering a pharmaceuti cal composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the targeting domain is at the C terminus of the peptide. In some aspects of the methods of treating cancer comprising administering a pharmaceutical composition comprising a cell, wherein the cell comprises a nucleic acid molecule capable of encoding a peptide, the targeting domain is ACE2.
[0326] In some aspects of the methods of treating cancer, the cancer is breast cancer, colon cancer, liver cancer, pancreatic cancer, prostate cancer or lung cancer. In some aspects of the methods of treating cancer, the cancer is pancreatic cancer or lung cancer.
[0327] In some aspects of the methods of treating cancer, LDH release is increased in cancer cells. In some aspects of the methods of treating cancer, LDH release is not increased in non-cancer cells.
[0328] In some aspects of the methods of treating cancer, MIT metabolism is decreased in cancer cells. In some aspects of the methods of treating cancer, MTT metabolism is not decreased in non-cancer cells.
[0329] In some aspects of the methods of treating cancer, the peptide, composition, or pharmaceutical composition is administered intranasally.2. Methods of Increasing LDH Release
[0330] Disclosed are methods of increasing LDH release in a subject in need thereof comprising administering to the subject an effective amount of any one of the peptides, nucleic acids, cells, compositions or pharmaceutical compositions disclosed herein to the subject.
[0331] Disclosed herein are methods increasing LDH release in a subject in need thereof comprising administering to tire subject an effective amount of a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0332] In some aspects of the methods increasing LDH release, the CPP is at the N terminus of the peptide. In some aspects of the methods increasing LDH release, the CPP is at the C terminus of the peptide.
[0333] In some aspects of the methods increasing LDH release, the CPP is cationic. In some aspects of the methods increasing LDH release, the CPP is non-amphipathic.
[0334] hi some aspects of the methods increasing LDH release, the CPP is the cellpenetrating domain of HIV- 1 Tat, In some aspects of the methods increasing LDH release, the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: I). In some aspects of the methods increasing LDH release, the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the methods increasing LDH release, the CPP is antennapedia homeodomain DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
[0335] hi some aspects of the methods increasing LDH release, the fragment of SARS- CoV-2 spike SI is from about 10 to 20 amino acids long.
[0336] In some aspects of the methods increasing LDH release, the fragment of SARS- CoV-2 spike SI is from 12 to 18 amino acids long. In some aspects of the methods increasing LDH release, the fragment of SARS-CoV-2 spike SI is from about 12 to 15 amino acids long.
[0337] In some aspects of the methods increasing LDH release, the fragment of SARS- CoV-2 spike SI is 10 amino acids long. In some aspects of the methods increasing LDH release, the fragment of SARS-CoV-2 spike SI is 11 amino acids long. In some aspects of the methods increasing LDH release, the fragment of SARS-CoV-2 spike SI is 12 amino acids long. In some aspects of the methods increasing LDH release, the fragment of SARS-CoV-2 spike SI is 13 amino acids long. In some aspects of the methods increasing LDH release, the fragment of SARS-CoV-2 spike SI is 14 amino acids long. In some aspects of the methods increasing LDH release, the fragment of SARS-CoV-2 spike SI is 15 amino acids long. In some aspects of the methods increasing LDH release, the fragment of SARS-CoV-2 spike SI is 16 amino acids long. In some aspects of the methods increasing LDH release, the fragment of SARS-CoV-2 spike SI is 17 amino acids long. In some aspects of the methods increasing LDH release, the fragment of SARS-CoV-2 spike SI is 18 amino acids long. In some aspects of the methods increasing LDH release, the fragment of SARS-CoV-2 spike S I is 19 amino acids long. In some aspects of the methods increasing LDH release, the fragment of SARS-CoV-2 spike SI is 20 amino acids long.
[0338] In some aspects of the methods increasing LDH release, the fragment of SARS- CoV-2 spike SI comprises all or part of the ACE2-Interacting Domain (ACID) of SARS-CoV -2 spike S 1. In some aspects of the methods increasing LDH release, the fragment of SARS-CoV-2 spike SI comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y. In some aspects of the methods increasing LDH release, the fragment of SARS-CoV-2 spike SI comprises theamino acid sequence NGVGY (SEQ ID NO: 7). In some aspects of the methods increasing LDH release, the fragment of SARS-CoV-2 spike SI comprises the ammo acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5), In some aspects of the methods increasing LDH release, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects of the methods increasing LDH release, the peptide is one or more of the sequences of Table 1. For example, disclosed herein are methods increasing LDH release with a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. Disclosed herein are methods increasing LDH release with a peptide comprising SEQ ID NO: 11,
[0339] In some aspects of the methods increasing LDH release, the disclosed peptides further comprise a targeting domain. In some aspects of the methods increasing LDH release, the targeting domain is at the N terminus of the peptide. In some aspects of the methods increasing LDH release, the targeting domain is at the C terminus of the peptide. In some aspects of the methods increasing LDH release, the targeting domain is ACE2.
[0340] hi some aspects of the methods of increasing LDH release, LDH release is increased in cancer cells. In some aspects of tire methods of increasing LDH release, LDH release is not increased in non-cancer cells.
[0341] In some aspects of the methods of increasing LDH release, the peptide, composition, or pharmaceutical composition is administered intranasally.3. Methods of Decreasing MTT Metabolism
[0342] Disclosed are methods of decreasing MT metabolism in a subject in need thereof comprising administering to the subject an effective amount of any one of the disclosed peptides, nucleic acids, vectors, cells, compositions or pharmaceutical compositions.
[0343] Disclosed herein are methods decreasing MTT metabolism in a subject in need thereof comprising administering to the subject an effective amount of a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide,
[0344] In some aspects of the methods of decreasing MTT metabolism, the CPP is at the N terminus of the peptide. In some aspects of the methods of decreasing MIT metabolism, the CPP is at the C terminus of the peptide.
[0345] In some aspects of the methods of decreasing MTT metabolism, the CPP is cationic. In some aspects of the methods of decreasing MTT metabolism, the CPP is non-aniphipathic.
[0346] In some aspects of the methods of decreasing MTT metabolism, the CPP is the cell-penetrating domain of HIV-1 Tat. In some aspects of the methods of decreasing MTTmetabolism, the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: 1), In some aspects of the methods of decreasing MTT metabolism, the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the methods of decreasing MTT metabolism, the CPP is antennapedia homeodomain DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
[0347] In some aspects of the methods of decreasing MTT metabolism, the fragment of SARS-CoV-2 spike SI is from about 10 to 20 amino acids long.
[0348] hi some aspects of the methods of decreasing MTT metabolism, the fragment of SARS-CoV-2 spike SI is from 12 to 18 amino acids long. In some aspects of the methods of decreasing MTT metabolism, the fragment of SARS-CoV-2 spike S 1 is from about 12 to 15 amino acids long.
[0349] In some aspects of the methods of decreasing MTT metabolism, the fragment of SARS-CoV-2 spike SI is 10 amino acids long. In some aspects of the methods of decreasing MTT metabolism, the fragment of SARS-CoV-2 spike S 1 is 11 amino acids long. In some aspects of the methods of decreasing MIT metabolism, the fragment of SARS-CoV-2 spike SI is 12 amino acids long. In some aspects of the methods of decreasing MTT metabolism, the fragment of SARS-CoV-2 spike SI is 13 amino acids long. In some aspects of the methods of decreasing MIT metabolism, the fragment of SARS-CoV-2 spike SI is 14 amino acids long. In some aspects of the methods of decreasing MTT metabolism, the fragment of SARS-CoV-2 spike SI is 15 amino acids long. In some aspects of the methods of decreasing MTT metabolism, the fragment of SARS-CoV-2 spike S 1 is 16 amino acids long. In some aspects of the methods of decreasing MTT metabolism, the fragment of SARS-CoV-2 spike SI is 17 amino acids long. In some aspects of the methods of decreasing MTT metabolism, the fragment of SARS-CoV-2 spike SI is 18 amino acids long. In some aspects of the methods of decreasing MIT metabolism, the fragment of SARS-CoV-2 spike SI is 19 amino acids long. In some aspects of the methods of decreasing MTT metabolism, the fragment of SARS-CoV-2 spike SI is 20 amino acids long.
[0350] hi some aspects of the methods of decreasing MTT metabolism, the fragment of SARS-CoV-2 spike SI comprises all or part of the ACE2-Interacting Domain (ACID) of SARS-CoV-2 spike SI. In some aspects of the methods of decreasing MTT metabolism, the fragment of SARS-CoV-2 spike SI comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y. In some aspec ts of the methods of decreasing MTT me tabolism, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence NGVGY (SEQ ID NO: 7). In some aspects ofthe methods of decreasing MIT metabolism, the fragment of SARS-CoV-2 spike S 1 comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5), In some aspects of the methods of decreasing MTT metabolism, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects of the methods of decreasing MTT metabolism, the peptide is one or more of the sequences of Table 1. For example, disclosed herein are methods of decreasing MTT metabolism with a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. Disclosed herein are methods of decreasing MIT metabolism with a peptide comprising SEQ ID NO: 11.
[0351] In some aspects of the methods of decreasing MTT metabolism, the disclosed peptides further comprise a targeting domain. In some aspects of the methods of decreasing MTT metabolism, the targeting domain is at the N terminus of the peptide. In some aspects of the methods of decreasing MTT metabolism, the targeting domain is at the C terminus of the peptide. In some aspects of the methods of decreasing MTT metabolism, the targeting domain is ACE2.
[0352] In some aspects of the methods of decreasing MTT metabolism, MTT metabolism is decreased in cancer cells. In some aspects of the methods of decreasing MTT metabolism, MTT metabolism is not decreased in non-cancer cells.
[0353] In some aspects of the methods of decreasing MTT metabolism, the subject has or has been diagnosed with pancreatic or lung cancer.
[0354] hi some aspects of the methods of decreasing MIT' metabolism, the peptide, composition, or pharmaceutical composition is administered mtranasally,4. Methods of Inducing Apoptosis
[0355] Disclosed are methods of inducing apoptosis in a subject in need thereof comprising administering to the subject an effective amount of any one of the disclosed peptides, nucleic acids, vectors, cells, compositions or pharmaceutical compositions.
[0356] Disclosed herein are methods inducing apoptosis in a subject in need thereof comprising administering to the subject an effective amount of a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0357] In some aspects of the methods of inducing apoptosis, the CPP is at the N terminus of the peptide. In some aspects of the methods of inducing apoptosis, the CPP is at the C terminus of the peptide.
[0358] In some aspects of the methods of inducing apoptosis, the CPP is cationic. In some aspects of the methods of inducing apoptosis, the CPP is non-amphipathic.
[0359] hi some aspects of the methods of inducing apoptosis, the CPP is the cellpenetrating domain of HIV- 1 Tat, In some aspects of the methods of inducing apoptosis, the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: 1). In some aspects of the methods of inducing apoptosis, the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the methods of inducing apoptosis, the CPP is antennapedia homeodomain DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
[0360] hi some aspects of the methods of inducing apoptosis, the fragment of SARS- CoV-2 spike SI is from about 10 to 20 amino acids long.
[0361] In some aspects of the methods of inducing apoptosis, the fragment of SARS- CoV-2 spike SI is from 12 to 18 amino acids long. In some aspects of the methods of inducing apoptosis, the fragment of SARS-CoV-2 spike SI is from about 12 to 15 amino acids long.
[0362] In some aspects of the methods of inducing apoptosis, the fragment of SARS- CoV-2 spike SI is 10 amino acids long. In some aspects of the methods of inducing apoptosis, the fragment of SARS-CoV-2 spike S 1 is 11 amino acids long. In some aspects of the methods of inducing apoptosis, the fragment of SARS-CoV-2 spike SI is 12 amino acids long. In some aspects of the methods of inducing apoptosis, the fragment of SARS-CoV-2 spike SI is 13 amino acids long. In some aspects of the methods of inducing apoptosis, the fragment of SARS-CoV-2 spike SI is 14 amino acids long. In some aspects of the methods of inducing apoptosis, the fragment of SARS-CoV-2 spike SI is 15 amino acids long. In some aspects of the methods of inducing apoptosis, the fragment of SARS-CoV-2 spike SI is 16 amino acids long. In some aspects of the methods of inducing apoptosis, the fragment of SARS-CoV-2 spike SI is 17 amino acids long. In some aspects of the methods of inducing apoptosis, tire fragment of SARS-CoV-2 spike SI is 18 amino acids long. In some aspects of the methods of inducing apoptosis, the fragment of S ARS-CoV -2 spike S 1 is 19 amino acids long. In some aspects of the methods of inducing apoptosis, the fragment of SARS-CoV-2 spike SI is 20 amino acids long.
[0363] In some aspects of the methods of inducing apoptosis, the fragment of S ARS- CoV-2 spike SI comprises all or part of the ACE2-Interacting Domain (ACID) of SARS-CoV -2 spike S 1. In some aspects of the methods of inducing apoptosis, the fragment of SARS-CoV-2 spike SI comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y. In some aspects of the methods of inducing apoptosis, the fragment of SARS-CoV-2 spike SI comprises theamino acid sequence NGVGY (SEQ ID NO: 7). In some aspects of the methods of inducing apoptosis, the fragment of SARS-CoV-2 spike S I comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5), In some aspects of the methods of inducing apoptosis, the fragment of SARS-CoV-2 spike S 1 comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects of the methods of inducing apoptosis, the peptide is one or more of the sequences of Table 1. For example, disclosed herein are methods of inducing apoptosis with a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. Disclosed herein are methods of inducing apoptosis with a peptide comprising SEQ ID NO: 11.
[0364] In some aspects of the methods of inducing apoptosis, the disclosed peptides further comprise a targeting domain. In some aspects of the methods of inducing apoptosis, the targeting domain is at the N terminus of the peptide. In some aspects of the methods of inducing apoptosis, the targeting domain is at the C terminus of the peptide. In some aspects of the methods of inducing apoptosis, the targeting domain is ACE2.
[0365] hi some aspects of the methods of inducing apoptosis, apoptosis of non-cancer cells is not increased.
[0366] In some aspects of the methods of inducing apoptosis, the subject has or has been diagnosed with pancreatic or lung cancer. In some aspects of the methods of inducing apoptosis, the cancer cells are pancreatic cancer or lung cancer cells.
[0367] In some aspects of the methods of inducing apoptosis, LDFI release is increased in the cancer cells. In some aspects of the methods of inducing apoptosis, LDH release is not increased in non-cancer cells.
[0368] In some aspects of the methods of inducing apoptosis, MTT metabolism is decreased in the cancer cells. In some aspects of the methods of inducing apoptosis, MIT metabolism is not decreased in non-cancer cells.
[0369] In some aspects of the methods of inducing apoptosis, the effective amount of the peptide, composition, or a pharmaceutical composition is administered intranasally.
[0370] hi some aspects of the methods of inducing apoptosis, the method further comprises administering chemotherapy or radiation.5. Methods of Reducing VEGF Expression
[0371] Disclosed are methods of reducing VEGF expression in a subject in need thereof comprising administering to the subject an effective amount of any one of the disclosed peptides, nucleic acids, vectors, cells, compositions or pharmaceutical compositions.
[0372] Disclosed are methods of reducing VEGF expression in a subject in need thereofcomprising administering to the subject an effective amount of a peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
[0373] In some aspects of the methods of reducing VEGF expression, the CPP is at the N terminus of the peptide. In some aspects of the methods of inducing apoptosis, the CPP is at the C terminus of the peptide,
[0374] In some aspects of the methods of reducing VEGF expression, the CPP is cationic. In some aspects of the methods of inducing apoptosis, the CPP is non-amphipathic.
[0375] In some aspects of the methods of reducing VEGF expression, the CPP is the cellpenetrating domain of HIV- 1 Tat, In some aspects of the methods of reducing VEGF expression, the CPP comprises the amino acid sequence YARAAARQARA (SEQ ID NO: 1). In some aspects of the methods of reducing VEGF expression, the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)). In some aspects of the methods of reducing VEGF expression, the CPP is antennapedia homeodomain DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
[0376] In some aspects of the methods of reducing VEGF expression, the fragment of SARS-CoV-2 spike SI is from about 10 to 20 amino acids long.
[0377] In some aspects of the methods of reducing VEGF expression, the fragment of SARS-CoV-2 spike SI is from 12 to 18 amino acids long. In some aspects of the methods of reducing VEGF expression, the fragment of S ARS-CoV-2 spike S I is from about 12 to 15 amino acids long.
[0378] In some aspects of the methods of reducing VEGF expression, the fragment of SARS-CoV-2 spike SI is 10 ammo acids long. In some aspects of the methods of reducing VEGF expression, the fragment of SARS-CoV-2 spike SI is 11 amino acids long. In some aspects of the methods of reducing VEGF expression, the fragment of SARS-CoV-2 spike SI is 12 amino acids long. In some aspects of the methods of reducing VEGF expression, the fragment of SARS-CoV-2 spike SI is 13 amino acids long. In some aspects of the methods of reducing VEGF expression, the fragment of SARS-CoV-2 spike SI is 14 amino acids long. In some aspects of the methods of reducing VEGF expression, tire fragment of SARS-CoV-2 spike SI is 15 ammo acids long. In some aspects of the methods of reducing VEGF expression, the fragment of SARS-CoV-2 spike SI is 16 amino acids long. In some aspects of the methods of reducing VEGF expression, the fragment of SARS-CoV-2 spike SI is 17 amino acids long. In some aspects of the methods of reducing VEGF expression, the fragment of SARS-CoV-2 spike SI is 18 amino acids long. In some aspects of the methods of reducing VEGF expression, the fragment of SARS-CoV-2 spike SI is 19 amino acids long. Insome aspects of the methods of reducing VEGF expression, the fragment of SARS-CoV-2 spike S1 is 20 amino acids long.
[0379] In some aspects of the methods of reducing VEGF expression, the fragment of SARS-CoV-2 spike SI comprises all or part of die ACE2 -Interacting Domain (ACID) of SARS-CoV-2 spike S 1. In some aspects of the methods of reducing VEGF expression, the fragment of SARS-CoV-2 spike S 1 comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the underlined amino acids S, N and Y. In some aspects of the methods of reducing VEGF expression, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence NGVGY (SEQ ID NO: 7). In some aspects of the methods of reducing VEGF expression, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5). In some aspects of the methods of reducing VEGF expression, the fragment of SARS-CoV-2 spike SI comprises the amino acid sequence QAYGFGPTGGVGD (SEQ ID NO: 6). In some aspects of the methods of reducing VEGF expression, the peptide is one or more of the sequences of Table 1. For example, disclosed herein are methods of reducing VEGF expression with a peptide comprising SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 or SEQ ID NO: 12. Disclosed herein are methods of reducing VEGF expression with a peptide comprising SEQ ID NO: 11.
[0380] In some aspects of the methods of reducing VEGF expression, the disclosed peptides further comprise a targeting domain. In some aspects of the methods of reducing VEGF expression, the targeting domain is at the N terminus of the peptide. In some aspects of the methods of reducing VEGF expression, the targeting domain is at the C terminus of the peptide. In some aspects of the methods of reducing VEGF expression, the targeting domain is ACE2.
[0381] In some aspects of the methods of reducing VEGF expression, the reduction of VEGF expression in non-cancer cells is not increased.
[0382] In some aspects of the methods of reducing VEGF expression, the subject has or has been diagnosed with pancreatic or lung cancer. In some aspects of the methods of reducing VEGF expression, the cancer cells are pancreatic cancer or lung cancer cells.
[0383] In some aspects of the methods of reducing VEGF expression, LDH release is increased in the cancer cells. In some aspects of the methods of reducing VEGF expression, LDH release is not increased in non-cancer cells.
[0384] In some aspects of the methods of reducing VEGF expression, MTT metabolism is decreased in the cancer cells. In some aspects of the methods of reducing VEGF expression, MTT metabolism is not decreased in non-cancer cells.
[0385] In some aspects of the methods of reducing VEGF expression, the effective amount of the peptide, composition, or a pharmaceutical composition is administered intranasal ly.
[0386] In some aspects of the methods of reducing VEGF expression, the method further comprises administering chemotherapy or radiation.
[0387] In some aspects of the methods of reducing VEGF expression in a subject, wherein the subject has cancer, angiogenesis of tumor of the subject is reduced. In some aspects of the methods of reducing VEGF expression in a subject, wherein the subject has cancer, endothelial proliferation around or near the tumor of the subject is reduced.6. Dosing Regimens
[0388] Disclosed are dosing regimens comprising at least one treatment cycle of an effective amount of any of the disclosed peptides, nucleic acid molecules, vectors, cells, compositions or pharmaceutical compositions.
[0389] Disclosed herein are dosing regimens in which the peptide, nucleic acid molecules, cells, compositions or pharmaceutical compositions is administered only once.
[0390] Disclosed herein are dosing regimens in which the peptide, nucleic acid molecules, cells, compositions or pharmaceutical compositions is administered multiple times over a period of time.
[0391] Treatment cycles can include the administration of different dosages of peptide, nucleic acid molecules, vectors, cells, compositions or pharmaceutical compositions as well as administration at different time points. The peptides, nucleic acid molecules, vectors, cells, compositions or pharmaceutical compositions can be administered for varying amounts of time for up to 6 months. The peptide, nucleic acid molecules, vectors, cells, compositions or pharmaceutical compositions can be administered for varying amounts of time indefinitely. In some instances, the administration can occur for up to one, two, three, four, five or six months. For example, the peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition can be administered once a week for 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, or 24 weeks. In some aspects the disclosed peptides, nucleic acid molecules, vectors, cells, compositions or pharmaceutical compositions can be administered about every 3, about every 6 or about every 12 months.
[0392] The length of time for each treatment cycle can vary depending on the amount of peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition administered per dosage. A treatment cycle can include the administration of peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition once, twice or threetimes a week. In some aspects, the peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition can be administered daily. In some aspects, the peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition can be administered once every two weeks or even once a month. In some instances, the peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition can be administered every two weeks for 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, or 24 weeks. For example, the treatment cycle can include administering a peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition once a week for four weeks or once every two weeks for up to six months. Thus, each treatment cycle includes an established length of time for administration as well as an established dosing schedule during that time frame.
[0393] In one aspect, more than one peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition can be administered during the treatment cycles. The more than one peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition can be formulated together or in separate compositions, In some instances, one or more peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition is administered in combination with one or more other therapeutic agents, including, but not limited to antibodies, nanobodies, aptamers, liposomes, antioxidants, anti-inflammator ’ agents, senolytic agents.7. Dose
[0394] The dose or dosage of peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition can vary depending on many factors, such as but not limited to, age, condition, sex and extent of the disease in the patient, route of administration, length of treatment cycle, or whether other drugs are included in the regimen, and can be determined by one of skill in the art.
[0395] Effective dosages can be determined empirically, and making such determinations is within the skill in the art. The dosage ranges for the administration of the compositions are those large enough to produce the desired effect in which the disease is treated. For example, the dosage can be an amount effective to provide therapeutic effects and provide or allow for sustained therapeutic effects even after the treatment (i.e. peptide) is withdrawn. The therapeutic effects can be, but are not limited to, a decrease in LDH release from cancer cells, an increase in MTT metabolism in cancer cells and / or an increase in apoptosis of cancer cells. Other biomarkers used to measure therapeutic effects can be markers of inflammation, such as cytokines, chemokines and / or adhesion molecules, markers of oxidative stress, and / ormarkers of cell death / apoptosis. Tire therapeutic effects can be measured by imaging techniques, including MRI, intravascular ultrasound, ultrafast imaging CT scans, B-mode ultrasonography, virtual histology intravascular ultrasound, optical coherence tomography, or other known methods.
[0396] The dosage should not be so large as to cause adverse side effects, such as unwanted cross-reactions, anaphylactic reactions, and the like. The dosage can be adjusted by the individual physician in the event of any counter-indications. Dosage can vary, and can be administered in one or more dose administrations daily, for one or several days. Guidance can be found in the literature for appropriate dosages for given classes of pharmaceutical products.
[0397] Suitable dosages include, but are not limited to amounts between 0.01 mg / kg and 20 mg / kg. For example, disclosed herein are methods involving administering one or more of the disclosed peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition to a subject, wherein the peptide is administered in an amount of about 0.01 mg / kg to about 20 mg / kg. For example, the concentration of the peptide can be 0.01, 0.1, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 mg / kg.
[0398] The peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition dose can be administered as a bolus injection or as an infusion over one or more hours.8. Delivery
[0399] In the methods described herein, administration or delivery of the peptides, nucleic acid molecules, vectors, cells, compositions or pharmaceutical compositions can be via a variety of mechanisms. As defined above, disclosed herein are methods of treating, dosing regimens and methods of using those dosing regimens to treat. The dosing regimens and methods include compositions containing any one or more of the polypeptides or nucleic acids described herein that can also include a carrier such as a pharmaceutically acceptable carrier. For example, disclosed are pharmaceutical compositions, comprising the peptides, nucleic acid molecules, vectors, cells and compositions disclosed herein, and a pharmaceutically acceptable carrier.
[0400] The disclosed peptides, nucleic acid molecules, vectors, cells, compositions or pharmaceutical compositions can be in solution or in suspension (for example, incorporated into microparticles, liposomes, or cells). These compositions can be targeted to a particular cell type via antibodies, receptors, or receptor ligands. One of skill in the art knows how to make and use such targeting agents with the disclosed compositions. A targeting agent canbe a vehicle such as an antibody conjugated liposomes; receptor mediated targeting of DNA through cell specific ligands, and highly specific retroviral targeting of cells in vivo. Any such vehicles can be part of the compositions herein. For example, targeting agents that direct the peptide, nucleic acid molecule, vector, composition or pharmaceutical composition to a cancer cell can be included in the compositions.
[0401] Any suitable route of administration can be used for the disclosed compositions. Suitable routes of administration can, for example, include topical, enteral, local, sy stemic, or parenteral. For example, administration can be epicutaneous, inhalational, enema, conjunctival, eye drops, ear drops, alveolar, nasal, intranasal, enteral, oral, intraoral, transoral, intestinal, rectal, intrarectal, transrectal, injection, infusion, intravenous, intraarterial, intramuscular, intracerebral, intraventricular, intracerebroventricular, intracardiac, subcutaneous, intraosseous, intradermal, intrathecal, intraperitoneal, intravesical, intracavemosal, intramedullar, intraocular, intracranial, transdermal, transmucosal, transnasal, inhalational, intracisternal, epidural, peridural, intravitreal, etc. The disclosed compositions can be used in and with any other therapy.
[0402] Nevertheless, in certain aspects, peptide delivery can be enhanced by the use of protective excipients. This is typically accomplished either by complexing the polypeptide with a composition to render it resistant to acidic and enzymatic hydrolysis or by packaging the polypeptide in an appropriately resistant carrier such as a liposome. Means of protecting polypeptides for oral delivery are well known in the art (see, e.g., U. S. Pat. No. 5,391,377 describing lipid compositions for oral delivery of therapeutic agents).
[0403] Elevated serum half-life can be maintained by the use of sustained-release protein "packaging" systems. Such sustained release systems are well known to those of skill in the art. In one preferred embodiment, the ProLease biodegradable microsphere delivery system for proteins and peptides (Tracy (1998) Biotechnol. Prog., 14: 108; Johnson et al. (1996) Nature Med. 2: 795; Herbert et al, (1998), Pharmaceut. Res, 15, 357) a dry’ powder composed of biodegradable polymeric microspheres containing the active agent in a polymer matrix that can be compounded as a dry formulation with or without other agents.
[0404] The ProLease microsphere fabrication process was specifically designed to achieve a high encapsulation efficiency while maintaining integrity of the active agent. The process consists of (i) preparation of freeze-dried drug particles from bulk by spray freeze-drying the drug solution with stabilizing excipients, (ii) preparation of a drug-polymer suspension followed by sonication or homogenization to reduce the drug particle size, (iii) production of frozen drug-polymer microspheres by atomization into liquid nitrogen, (iv)extraction of the polymer solvent with ethanol, and (v) filtration and vacuum drying to produce the final dry-powder product. The resulting powder contains the solid form of the active agents, which is homogeneously and rigidly dispersed within porous polymer particles. The polymer most commonly used in the process, poly(lactide-co-glycolide) (PLG), is both biocompatible and biodegradable.
[0405] Encapsulation can be achieved at low temperatures (e.g., -40° C ). During encapsulation, the protein is maintained in the solid state in the absence of water, thus minimizing water-induced conformational mobility of the protein, preventing protein degradation reactions that include water as a reactant, and avoiding organic -aqueous interfaces where proteins may undergo denaturation. A preferred process uses solvents in which most proteins are insoluble, thus yielding high encapsulation efficiencies (e.g., greater than 95%).
[0406] In another embodiment, one or more components of the solution can be provided as a "concentrate", e.g., in a storage container (e.g., in a premeasured volume) ready for dilution, or in a soluble capsule ready for addition to a volume of water.
[0407] The foregoing formulations and administration methods are intended to be illustrative and not limiting. It will be appreciated that, using the teaching provided herein, other suitable formulations and modes of administration can be readily devised.9. Combination Therapy
[0408] In one aspect of the disclosed methods, the peptides, nucleic acid molecules, vectors, cells, compositions or pharmaceutical compositions can be administered alone or in combination with one or more additional therapeutic agents. The additional therapeutic agents are selected based on the disease or symptom to be treated. A description of the various classes of suitable pharmacological agents and drugs may be found in Goodman and Gilman, The Pharmacological Basis of Therapeutics, (11th Ed., McGraw-Hill Publishing Co.) (2005). For example, pharmaceutical compositions containing peptides can be administered in combination with one or more known therapeutic agents for treating cancer.
[0409] Examples of therapeutic agents that treat vascular disease, cognitive dysfunction and / or neurodegeneration include, but are not limited to, anti -inflammatory’ agents, antioxidant agents, senolytic agents, lipid lowering agents and liposomes.
[0410] The peptides can be administered in conjunction with or followed by any of the disclosed additional therapeutics.
[0411] The combination therapies can include administering the peptide, nucleic acid molecule, vector, cell, composition or pharmaceutical composition and an additionaltherapeutic agent during the treatment cycle of a dosing regimen.EXAMPLES
[0412] It is understood that the disclosed method and compositions are not limited to the particular methodology, protocols, and reagents described as these may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention which will be limited only by the appended claims.
[0413] Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the method and compositions described herein. Such equivalents are intended to be encompassed by the following claims.Example 1: Designing of ACID peptides + HIV-Tat
[0414] Described herein is the engineering of an example of the disclosed peptides that can be used to induce cancer cell death.Designing of ACID peptides
[0415] From in silico analysis of the interaction of SARS-CoV-2 spike SI and human ACE2 (FIG. 1), we designed ACID peptides. The wild type and mutated ACID peptides are:
[0416] Wild type (wt) ACID: yaraaarqaraQSYGFQPTNGVGY (SEQ ID NO: 9)
[0417] Mutated (m) ACID: yaraaarqaraQAYGFGPTGGVGD (SEQ ID NO: 10)
[0418] The positions of mutations are underlined. The cell-penetrating domain of the HIV-1 Tat (lowercase) at the N-terminal of these peptides to facilitate cell permeability. Effect of wtACID and mACID peptides on the survival of human PANC-1 pancreatic cancer cells and normal human pancreatic duct epithelial (HPDE) cells
[0419] The effect of wtACID and mACID peptides on the survival of PANC-1 and HPDE cells was tested by measuring LDH release and MTT metabolism. An increase in LDH release (Fig. 2A) and decrease in MTT metabolism (Fig. 2B) by wtACID in PANC-1 cells was observed, indicating that wtACID is capable of inducing death in PANC-1 cells. In contrast, wtACID remained unable to increase LDH release (Fig. 2C) and decrease in MTT metabolism (Fig. 2D) in HPDE cells, suggesting that wtACID is not toxic to normal HPDE cells. On the other hand, mACID peptide remained unable to induce death in either PANC-1 or HPDE cells (Fig. 2A-D), indicating the specificity of ACID peptides.Effect of wtACID and mACID peptides on the survival of human Hl 299 lung cancer cells and normal BEAS-2B human bronchial epithelial cells
[0420] The effect of wtACID and mACID peptides on the survival of H1299 and BEAS-2B cells was also tested. wtACID induced cell death in H1299 lung cancer cells (LDH release, Fig. 3A; MTT metabolism. Fig. 3B), but not BEAS-2B normal lung cells (LDH release, Fig. 3C; MTT metabolism, Fig. 3D). Similar to that found in pancreatic cancer cells, mACID remained unable to increase LDH release and decrease MTT in either H1299 or BEAS-2B cells (Fig. 3A-D).Effect of wtACID and mACID peptides on tumor regression in a patient-derived xenograft (PDX) mouse model of pancreatic cancer
[0421] Female 6-8-weeks old NOD scid gamma mice were engrafted with pancreatic ductal adenocarcinoma tumor fragments in tlie flank. When tumors reached 0.4 cm2, mice were treated with wtACID intranasally at different doses (0.1 and 0.2 mg / kg body wt / day. After 4 weeks of wtACID treatment, there was no significant reduction in pancreatic tumor size in PDX mice.Example 2: ACID peptides + Antennapedia homeodomain
[0422] For this experiment the ACID peptides were:
[0423] Wild type (wt) ACID: drqikiwfqnrrmkwkkQSYGFQPTNGVGY (SEQ ID NO: 11)
[0424] Mutated (m) ACID: drqikiwfqnrrmkwkkQAYGFGPTGGVGD (SEQ ID NO: 12)
[0425] The positions of mutations are underlined. The Antennapedia homeodomain (lowercase) at the N-terminal of these peptides was used to facilitate cell permeability. Specificity of the wtACID and mACID peptides
[0426] The specificity of the wtACID and mACID peptides was tested using surface plasmon resonance (SPR). The SPR assay showed that wtACID, but not mACID, peptide is capable of binding to ACE2 protein (Figs. 4A-4B), indicating the specificity of effect.Effect of new wtACID and mACID peptides on the apoptosis of human pancreatic cancer cells and normal human pancreatic cells
[0427] When the ACID peptides w'ere investigated in human pancreatic cancer cells, it was found that the wtACID was capable of inducing apoptosis in human pancreatic cancer cells PANCI (Figs. 5C & 5F) and BXPC3 (Figs. 5B & 5E), but not normal pancreatic cells HPDE (Figs. 5 A & 5D). Therefore, wtACID was not be toxic to normal pancreatic cells. In contrast to wtACID, mACID did not induce apoptosis in either pancreatic cancer cells (PANC1 and BXPC3) or normal pancreatic cells (HPDE) (Figs. 5A-5F).Effect of new wtACID peptide on tumor growth in PDX mouse model of pancreatic cancer
[0428] Efficacy of the wtACID peptide containing Antennapedia homeodomain CPD in vivo in the PDX mouse model of pancreatic cancer was also examined. The PDX model (ID# TM01212; Jackson Lab) was used for this study. In this model, cryopreserved tissue obtained from patients with pancreatic cancer was minced and implanted subcutaneously into the NOD scid gamma (NSG) mouse's fat pad. The wtACID peptide was dissolved in normal saline and when tumors reached 50 mm2, PDX mice were treated with wtACID at a dose of 0.1 mg / kg body wt / d intranasally. Mice were held in a supine position and treated with 2 pl saline containing wtACID through each nostril by using pipetman. As a result, mice were treated with a total volume of 4 pl saline containing wtACID. Control PDX mice also received 4 pl saline intranasally. As shown in Fig. 6A, treatment with wtACID reduced tumor size. Tumor measurements showed that the wt ACID-treated PDX mice had smaller tumors compared to control or PDX mice (Fig. 6B).Effect of new wtACID peptide on the apoptosis of tumor in PDX mouse model of pancreatic cancer
[0429] Programmed cell death or apoptosis in tumor tissues was measured by TUNEL assay. Very few TUNEL-positive bodies were found in tumors of untreated PDX mice (Figs.6C-6D). However, significant increase in TUNEL-positive bodies was observed in tumors of wtACID-treated PDX mice as compared to untreated PDX mice (Figs. 6C-6D).Effect of new wtACID peptide on angiogenesis markers in tumor of PDX mouse model of pancreatic cancer
[0430] Angiogenesis is the formation of new blood vessels, which plays a crucial role for tumor growth and metastasis in pancreatic cancer. Vascular Endothelial Growth Factor (VEGF) - VEGF receptor (VEGFR) signaling is a key driver of this process by stimulating endothelial cell proliferation. Therefore, the status of VEGF and VEGFR in tumors of wtACID-treated PDX mice was examined. Tumor tissues in PDX mice readily expressed both VEGF (Figs. 7A-7B) and VEGFR2 (Figs. 8A-8B). However, wtACID treatment markedly reduced the expression of VEGF (Figs. 7A-7B) and VEGFR2 (Figs. 8A-8B) in vivo in tumors of PDX mice, indicating that wtACID is capable of suppressing angiogenic signaling in pancreatic tumors of PDX mice.Effect of new wtACID and mACID peptides on the apoptosis of human lung cancer cells and normal human lung epithelial cells
[0431] The effect of wtACID and mACID peptides on the apoptosis of human lung cancer cells (H1299 and A549) and normal human bronchial epithelial cells (BEAS-2B) was tested. TUNEL staining showed that wtACID induced apoptosis in A549 (Figs. 9B & 9E) andH1299 (Figs. 9C & 9F) lung cancer cells, but not BEAS-2B (Figs. 9A & 9D) normal lung cells, indicating that wtACID is not toxic for normal lung cells. mACID peptide had no effect in either lung cancer cells (A549 and H1299) or normal lung epithelial cells (BEAS-2B) (Figs. 9A-F), indicating the specificity of wtACID peptides.
[0432] It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the scope or spirit of the invention. Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention being indicated by the following claims.
Claims
CLAIMSWe claim:
1. A peptide comprising: a) a cell penetrating peptide (CPP) and b) a fragment of the SARS-CoV-2 spike SI peptide.
2. The peptide of claim 1, wherein the CPP is at the N-terminus of the peptide.
3. The peptide of claim 1, wherein the CPP is at the C -terminus of the peptide.
4. The peptide of any one of claims 1 to 3, wherein the CPP is cationic.
5. The peptide of any one of claims 1 to 4, wherein the CPP is non-amphipatliic.
6. The peptide of any one of claims 1 to 5, wherein the CPP is the cell-penetrating domain of HIV- 1 Tat.
7. The peptide of claim 6, wherein the CPP comprises the amino acid sequence DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
8. The peptide of any one of claims 1 to 5, wherein the CPP is polyarginine (RRRRRRRRR (SEQ ID NO: 2) or RRRRRRRRRRR (SEQ ID NO: 3)) or antennapedia homeodoinain DRQIKIWFQNRRMKWKK (SEQ ID NO: 4).
9. The peptide of any one of claims 1 to 8, wherein the fragment of SARS-CoV-2 spike SI is about 10-20 amino acids long.
10. The peptide claim 9, wherein the fragment of SARS-CoV-2 spike S I is about 12-15 amino acids long,11. The peptide of any one of claims 1 to 10, wherein the fragment of SARS-CoV-2 spike SI comprises all or part of the ACE2-Interactmg Domain (ACID) of SARS-CoV-2 spike SI.
12. The peptide of any one of claims 1 to 11, wherein the fragment of SARS-CoV-2 spike SI comprises at least 70% identity to the sequence QSYGFQPTNGVGY (SEQ ID NO: 5) and comprises the amino acids S, N and Y of the amino acid sequence QSYGFQPTNGVGY(SI ) ID NO: 5).
13. The peptide of any one of claims 1 to 11, wherein the fragment of SARS-CoV-2 spike SI comprises the ammo acid sequence NGVGY (SEQ ID NO: 7).
14. The peptide of any one of claims 1 to 13, wherein the fragment of SARS-CoV-2 spike SI comprises the ammo acid sequence QSYGFQPTNGVGY (SEQ ID NO: 5).
15. The peptide of any one of claims 1 to 14, wherein the peptide further comprises a targeting domain.
16. The peptide of claim 15, wherein the targeting domain is at the N terminus of the peptide.
17. The peptide of claim 15, wherein the targeting domain is at the C terminus of the peptide.
18. The peptide of any one of claims I to 17, wherein the targeting domain is ACE2.
19. The peptide of any one of claims 1 to 18, wherein the peptide is drqikiwfqnrrmkwkkQSYGFQPTNGVGY (SEQ ID NO: 11).
20. A nucleic acid molecule capable of encoding the peptide of any one of claims 1 -19.
21. A vector comprising the nucleic acid molecule of claim 20,22. A cell comprising the peptide of any one of claims 1-19, the nucleic acid molecule of claim 20, or the vector of claim 21.
23. A composition comprising the peptide of any one of claims 1-19, the nucleic acid molecule of claim 20, the vector of claim 21, or the cell of claim 22.
24. A pharmaceutical composition comprising a) the peptide of any one of claims 1 -19, the nucleic acid molecule of claim 20, the vector of claim 21, the cell of claim 22, or the composition of claim 23 and b) a pharmaceutically acceptable carrier.
25. A method of treating cancer in a subject in need thereof comprising administering an effective amount of the peptide of any one of claims 1-19, the nucleic acid molecule of claim 20, the vector of claim 21, the cell of claim 22, the composition of claim 23, or the pharmaceutical composition of claim 24.
26. The method of claim 25, wherein the cancer is breast cancer, colon cancer, liver cancer, pancreatic cancer, prostate cancer or lung cancer.
27. The method of claim 26, wherein the cancer is pancreatic cancer or lung cancer.
28. The method of any one of claims 25 to 27, wherein LDH release is increased in cancer cells.
29. The method of any one of claims 25 to 28, wherein LDH release is not increased in non-cancer cells.
30. The method of any one of claims 25 to 29, wherein MTT metabolism is decreased in cancer cells.
31. The method of any one of claims 25 to 30, wherein MTT metabolism is not decreased in non-cancer cells.
32. The method of any one of claims 25 to 31, wherein the peptide, composition, or pharmaceutical composition is administered intranasally.
33. A method of increasing LDH release in a subject in need thereof comprising administering an effective amount of the peptide of any one of claims 1-19, the nucleic acid molecule of claim 20, the vector of claim 21, the cell of claim 22, the composition of claim 23, or the pharmaceutical composition of claim 24.
34. The method of claim 33, wherein LDH release is not increased in non-cancer cells.
35. A method of decreasing MTT metabolism in a subject in need thereof comprising administering an effective amount of the peptide of any one of claims 1-19, the nucleic acidmolecule of claim 20, the vector of claim 21, the cell of claim 22, the composition of claim 23, or the pharmaceutical composition of claim 24.
36. The method of claim 35, wherein MTT metabolism is not decreased in non-cancer cells.
37. The method of any one of claims 33 to 36, wherein the subject has or has been diagnosed with pancreatic or lung cancer.
38. The method any one of claims 33 to 37, wherein the peptide, composition, or pharmaceutical composition is administered intranasally.
39. A method of inducing apoptosis of cancer cells in a subject in need thereof comprising administering an effective amount of the peptide of any one of claims 1-19, the nucleic acid molecule of claim 20, the vector of claim 21, the cell of claim 22, the composition of claim 23, or the pharmaceutical composition of claim 24.
40. The method of claim 39, wherein apoptosis of non-cancer cells is not increased.
41. The method of claim 39 or claim 40, wherein the subject has or has been diagnosed with pancreatic or lung cancer.
42. The method of any one of claims 39 to 41, wherein the cancer cells are pancreatic cancer or lung cancer cells.
43. The method of any one of claims 39 to 42, wherein LDH release is increased in the cancer cells.
44. The method of any one of claims 39 to 43, wherein LDH release is not increased in non-cancer cells,45. The method of any one of claims 39 to 44, wherein MTT metabolism is decreased in the cancer cells.
46. The method of any one of claims 39 to 45, wherein MTT metabolism is not decreased in non-cancer cells.
47. The method of any one of claims 39 to 46, wherein the effective amount of the peptide, composition, or a pharmaceutical composition is administered mtranasally.
48. The method of any one of claims 25 to 47, further comprising administering chemotherapy or radiation.