Peptoids for inhibition of nasal pathogen infections, and compositions and methods for administration thereof

Abstract

Compositions for use in preventing or treating an infection of the nasal passages, sinuses, or both of a subject are described. The compositions include one or more peptoid compounds in an amount effective to prevent or treat the infection in the nasal passages, sinuses, or both. The compositions include the one or more peptoid compounds in an amount effective to inhibit one or more pathogenic bacteria, pathogenic fungus, or pathogenic virus in the nasal passages, sinuses, or both, while having relatively little or no activity against commensal bacterial species, commensal fungal species, commensal viral species, or any combination thereof, in the nasal passages, sinuses, or both of the subject.

Description

[0001] Attorney Docket No. : 118433-0117

[0002] PEPTOIDS FOR INHIBITION OF NASAL PATHOGEN INFECTIONS, AND COMPOSITIONS AND METHODS FOR ADMINISTRATION THEREOF

[0003] RELATED APPLICATIONS

[0004] This application claims the benefit of U.S. Provisional Application No. 63 / 736,792 filed December 20, 2024, and U.S. Provisional Application No. 63 / 898,700 filed October 14, 2025, the contents of which is hereby incorporated by reference herein in their entireties.

[0005] TECHNICAL FIELD

[0006] The present disclosure relates to methods of preventing and treating nasal infections, including infections of one or more pathogenic bacteria, fungi, or viruses.

[0007] BACKGROUND

[0008] One problem with commonly used existing antibiotics is that they often kill commensal bacteria, fungi, or viruses in the nasal passages, sinuses, or both, along with the harmful pathogens. This disruption of the nasal microbiome can lead to an imbalance, potentially making the nasal passages, sinuses, or both, more susceptible to infections and other issues. However, development of compounds and compositions that are effective for treating pathogenic nasal infections while sparing commensal bacteria, fungi, or viruses is challenging.

[0009] SUMMARY

[0010] The present disclosure relates in several embodiments to peptoid compounds, compositions and method of use thereof for treating or preventing nasal infections.

[0011] According to a first aspect, the present disclosure relates in several embodiments to compositions for use in preventing or treating an infection in the nasal passages, sinuses, or both of a subject, the composition comprising one or more peptoid compounds in an amount effective to prevent or treat the infection of the nasal passages, sinuses, or both.

[0012] The compositions may include but not limited to the following details, which can be combined with one another in any combinations unless clearly mutually exclusive:

[0013] (i) the one or more peptoids may be selected from: a peptoid compound H-Ntridec- NLys-Nspe-Nspe-NLys- NH2; a peptoid compound H-Ntetradec-NLys-Nspe-Nspe-NLys- NH2; a peptoid compound H-Ndec-Nlys-Nspe-Nspe(p-Br)-Nlys-Npse-Nspe(p-Br)-NH2; and a combination thereof, wherein each peptoid is in an amount effective to prevent or treat the infection of the nasal passages, sinuses, or both.

[0014] (ii) the infection may be a pathogenic bacteria infection, a pathogenic fungus infection, a pathogenic virus infection, or a combination thereof, wherein the infection is associated with a pathogenic disease of the nasal passages, sinuses, or both, or a pathogenic condition of the nasal passages, sinuses, or both.

[0015] (iii) the pathogenic bacteria may be selected from the group consisting of but not limited to: Acinetobacter spp., Bacteroides spp., Citrobacter spp., Corynebacterium spp., Enterobacter spp., Enterococcus spp., Escherichia coli, Fusobacterium spp., Haemophilus influenzae, Klebsiella spp., Moraxella catarrhalis, Mycobacterium spp., Peptostreptococcus spp., Porphyromonas spp., Prevotella spp., Cutibacterium acnes. Proteus spp., Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus spp., Streptococcus spp., and any combinations thereof.

[0016] (iv) the pathogenic fungus may be selected from the group consisting of Altemaria spp., Apiospermum spp., Aspergillus spp., Bipolaris spp., Blastomyces dermatitidis, Candida spp., Chrysosporium spp., Cladosporium spp., Coccidioides spp., Cryptococcus neoformans, Curvularia spp., Drechslera spp., Emericella nidulans, Exserohilum spp., Histoplasma spp., Mucor spp., Myriodontium keratinophilum, Paecilomyces spp., Paracoccidioides spp., Penicillium melinii, Pseudallescheria boydii, Rhizopus spp., Scedosporium spp., Schizophyllum commune, Sporothrix schenckii, and any combinations thereof.

[0017] (v) the pathogenic virus may be selected from the group consisting of Adenovirus, Coronavirus, Cytomegalovirus (CMV) (in immunocompromised), Echovirus, Human metapneumovirus (HMPV), Influenza virus, Parainfluenza virus, Rhinovirus and any combinations thereof.

[0018] (vi) the effective amount of the composition may not inhibit growth of a commensal bacteria species, a commensal fungal species, a commensal virus species, or any combination thereof.

[0019] (vii) the effective amount of the composition may inhibit growth of a commensal bacteria species, commensal fungal species, a commensal virus species, or any combination thereof by no more than 99%, 90%, 75%, 66%, 50%, 40%, 30%, 20%, 10%, 5%, 2%, or 1%, or wherein the effective amount of the composition inhibits growth of a commensal bacteria species, a commensal fungal species, a commensal virus species, or any combination thereof, by no more than a 2 log reduction. (viii) the commensal bacteria species may be selected from the group consisting of

[0020] Acinetobacter spp. (e.g., A. junii, A. indicus), Acidocella spp., Aeromonas spp.,

[0021] Aggregatibacter spp., Alicycliphilus spp., Asticcacaulis spp., Bradyrhizobium spp.,

[0022] Chryseobacterium spp., Citrobacter spp., Cloacibacterium spp., Clostridium spp.,

[0023] Coprobacillus spp. Corynebacterium spp. (e.g., C. accolens, C. amycolatum, C. aurimucosum, C. propinquum, C. pseudodiphtheriticum, C. segmentosum, C. striatum, C. tuber culostearicum), Cutibacterium spp. (e.g., C. acnes), Di aphorob acter spp.,

[0024] Dolosigranulum spp. (e.g., D. pigrum), Elizabethkingia spp. (e.g., A. anopheles),

[0025] Enterob acter spp., Escherichia spp., Exiguobacterium spp., Flavobacterium spp.,

[0026] Fusobacterium spp., Haemophilus spp. (e.g., H. influenzae), Helicobacter spp.,

[0027] Hyphomicrobiaceae (family), Klebsiella spp., Lactobacillus spp. (e.g., L. sakei),

[0028] Lawsonella spp., Leptotrichia spp., Micrococcus spp. (e.g., AL luteus),

[0029] Moraxella spp. (e.g., AL catarrhalis), Neisseria spp. (e.g., A. subflava, N. flavescens), Paenibacillus spp., Pedobacter spp., Peptoniphilus spp., Prevotella spp. (e.g., P. melaninogenica), Propionib acterium spp. (e.g., P. acnes, P. avidum, P. granulosum),

[0030] Pseudoalteromonas spp., Pseudomonas spp. (e.g., P. aeruginosa, P. oleovorans),

[0031] Ralstonia spp. (e.g., R. pickettii), Rheinheimera spp., Shewanella spp., Sphingobacterium spp., Staphylococcus spp. (e.g., S. aureus, S. capitis, S. epidermidis, S. hominis, S. lugdunensis), Stenotrophomonas spp. (e.g., S. maltophilia), Streptococcus spp. (e.g., S. mitis, S. parasanguinis, S. pneumoniae, S. pyogenes, S. salivarius), Streptomyces spp., Veillonella spp. (e.g., V. atypica, V. dispar, V. parvula), Vibrio spp, and any combinations thereof.

[0032] (ix) the commensal fungal species may be selected from the group consisting of Altemaria spp. (e.g., A. alternata, A. breviramosa), Aspergillus spp. (e.g., A. fumigatus, A. penicillioides), Aureobasidium spp. (e.g., A. pullulans), Bipolaris spp. (e.g., B. papendorfii), Cladosporium spp. (e.g., C. cladosporioides, C. delicatulum), Coniochaeta spp. (e.g., C. fasciculata), Cryptococcus spp. (e g-, C. neoformans), Fusarium spp., Malassezia spp. (e.g., AL globosa, M. restricta), Penicillium spp. (e.g., P. chrysogenum), Pleosporales (order), Rhodosporidium spp. (e.g., R. diabovatum), Saccharomyces spp., Scutellospora spp., Trichosporon spp, and any combinations thereof.

[0033] (x) the commensal virus may be selected from the group consisting of

[0034] Adenoviridae (family), Alphacoronavirus (genus), Anellovirus (genus),

[0035] Betacoronavirus (genus), Cystovirus (genus) Enterovirus (genus), Herpesviridae (family), Klebsiella phages (various strains), Lambda-like viruses (genus), Myovirus (genus), N4-like viruses (genus), Papillomaviridae (family), Pseudomonas virus phi 12 (species), Rhinovirus (genus), Siphovirus (genus), Tl-like viruses (genus), and any combinations thereof.

[0036] (xi) the composition may be formulated for intranasal administration.

[0037] (xii) the effective amount for intranasal administration may be from 0.1 - 100 mg / Kg / day, 0.5 - 80 mg / Kg / day, 1 - 50 mg / Kg / day, or 2 - 30 mg / Kg / day.

[0038] (xiii) the composition may be formulated for administration one, two, three, or four times per day, once per week, once every two weeks, or once per month, or any combinations thereof.

[0039] According to a second aspect, the present disclosure relates in several embodiments to a method of preventing or treating an infection of the nasal passages, sinuses, or both, of a subject. The method includes administering a composition described herein in an amount effective to prevent or treat the infection of the nasal passages, sinuses, or both.

[0040] BRIEF DESCRIPTION OF THE DRAWINGS

[0041] The present disclosure may be further understood through reference to the attached figures in combination with the detailed description that follows.

[0042] FIG. 1 is the molecular structure of peptoid compound MXB-24,656.

[0043] FIG. 2 is the molecular structure of peptoid compound MXB-22,510.

[0044] FIG. 3 is the molecular structure of peptoid compound MXB-27,369.

[0045] FIG. 4 is the molecular structure of peptoid compound MXB-25,605.

[0046] FIG. 5 is the molecular structure of peptoid compound MXB-24,816.

[0047] FIG. 6 is the molecular structure of peptoid compound MXB-25,739.

[0048] FIG. 7 is a schematic of an example study schedule testing MXB-22,510 in a nonhuman primate model of chronic rhinosinusitis.

[0049] FIG. 8 is a graph reporting example results of treating MRSA infection in nonhuman primate nasal cavity using peptoid MXB-22,510 and control.

[0050] FIG. 9 is a graph reporting example results of treating Candida albicans infection in nonhuman primate nasal cavity using peptoid MXB-22,510 and control.

[0051] FIG. 10 A, FIG. 10B and FIG. 10C are graphs reporting example results of increase in alpha diversity of nasal microbiome in nonhuman primate nasal cavity using peptoid MXB- 22,510 and control. FIG. 10D is a graph reporting example results of increase in beta diversity of nasal microbiome in nonhuman primate nasal cavity using peptoid MXB-22,510 and control.

[0052] DETAILED DESCRIPTION

[0053] The present disclosure relates to peptoid compounds for preventing or treating nasal infections. The present disclosure also relates to compositions that include one or more peptoid compounds, and methods of using the compositions for administering to the nasal passages, sinuses, or both, of a subject for preventing or treating a nasal infection in a subject. The compositions include one or more peptoid compounds that have activity against pathogens in a subject’s nasal passages, sinuses, or both, while having relatively little or no activity against commensal bacteria, fungi, or viruses that reside in the subject’s nasal passages, sinuses, or both. In various embodiments, the present disclosure relates to selective inhibition of nasal pathogens by administering an effective amount of one or more peptoid compounds disclosed herein provided in compositions suitable for intranasally administering to a subject’s nasal passages, sinuses, or both, including but not limited to pharmaceutical compositions and dosage forms thereof.

[0054] The nasal cavities and paranasal sinuses comprise a system of interconnected air-filled spaces within the skull. The nasal cavities are a pair of passages positioned above the roof of the mouth (hard palate) and behind the nose, extending posteriorly to connect with the nasopharynx, while the paranasal sinuses are four paired cavities (frontal, ethmoid, sphenoid, and maxillary) within the surrounding facial bones that drain into the nasal cavities. Divided into left and right sections by the nasal septum, this sinonasal system represents the most superior (cephalic) portion of the respiratory tract, communicating anteriorly with the external environment through the nares (nostrils) and serving functions such as olfaction, air filtration, humidification, and warming. Lined with a mucous membrane (respiratory epithelium) and ciliated cells, these structures provide a moist, warm environment that hosts a diverse microbiome of commensal and potentially pathogenic bacteria, fungi, and viruses.

[0055] The human nasal microbiome refers to a diverse community of microorganisms, including bacteria, fungi, viruses, and other microbes, that inhabit the nasal passages and sinuses. This ecosystem extends from the nostrils (anterior nares) to the upper throat and includes the paranasal sinuses, forming a distinct microbial niche separate from other body sites such as the oral cavity or gut. Colonization begins in early infancy, with the microbial composition typically stabilizing by around three years of age, influenced by factors such as mode of birth, environment, diet, and exposure to antibiotics.

[0056] In healthy individuals, the nasal microbiome is characterized by high diversity and balance, dominated by bacterial genera including but not limited to Coryne bacterium, Staphylococcus (e.g., S. aureus and S. epidermidis), Propionibacterium (e.g., P. acnes), Moraxella, and Dolichospermum in the nasal vestibule and sinonasal tract. Fungi (e.g., species from Aspergillus or Candida) and viruses (e.g., bacteriophages and respiratory viruses) are also present but in lower abundances, contributing to the overall microbial dynamics. This community plays a crucial role in maintaining mucosal integrity, modulating local immune responses, and providing colonization resistance against pathogens through mechanisms like competitive exclusion, production of antimicrobial compounds, and enhancement of mucociliary clearance.

[0057] Variations in the nasal microbiome can occur due to age, geography, seasonality, and health status. For instance, children and older adults may exhibit different bacterial profiles compared to young adults, with shifts during acute infections like the common cold. In disease states, such as chronic rhinosinusitis (CRS) or nasal polyposis, dysbiosis often emerges, marked by reduced microbial diversity, depletion of beneficial species, and overgrowth of opportunistic pathogens like Staphylococcus aureus, Pseudomonas aeruginosa, o Haemophilus influenzae. This imbalance can exacerbate inflammation, impair sinus healing, and contribute to persistent symptoms.

[0058] Accordingly, the nasal passages and sinuses (collectively the sinonasal region) host a complex microbiome comprising commensal bacteria, fungi, and viruses that play essential roles in maintaining mucosal health, immune modulation, and pathogen resistance.

[0059] The human nasal passages and sinuses serve as a protective barrier against external pathogens while hosting a diverse ecosystem of microorganisms, collectively known as the nasal microbiome. This ecosystem includes bacteria, fungi, and viruses, many of which are commensal — typically living on or within the host without causing harm or deriving benefit, though some may provide indirect benefits by competing with pathogens.

[0060] However, infections in the sinonasal region — such as acute or chronic rhinosinusitis (CRS) often involve pathogenic bacteria (e.g., Staphylococcus aureus, Streptococcus pneumoniae), fungi (e.g., Aspergillus fumigatus, Candida spp.), or viruses (e.g., rhinovirus, influenza). Current pharmacological treatments, particularly antibiotics and antifungals, frequently employ broad-spectrum agents that indiscriminately target both pathogens and beneficial commensals. This non-selective action leads to dysbiosis — an imbalance in the microbial community — resulting in short- and long-term consequences like reduced microbial diversity, increased infection susceptibility, antimicrobial resistance, and prolonged inflammation.

[0061] For example, currently used antibiotics are the cornerstone of treatment for bacterial rhinosinusitis, with common agents including amoxicillin-clavulanate (Augmentin), cephalosporins (e.g., cefuroxime), macrolides (e.g., azithromycin), and fluoroquinolones (e.g., levofloxacin). These drugs are often prescribed empirically for acute exacerbations or CRS, especially when bacterial superinfection follows a viral illness. However, most are broadspectrum, affecting a wide range of Gram-positive and Gram-negative bacteria, which inadvertently depletes commensal species like Corynebacterium accolens, Dolosigranulum pigrum, and Staphylococcus epidermidis. These commensals contribute to colonization resistance by producing antimicrobial peptides, competing for nutrients, and modulating immune responses (e.g., via short-chain fatty acids).

[0062] The primary problem associated with currently used antibiotics is the induction of dysbiosis. A single course of oral antibiotics can alter the sinonasal microbiome for up to two years, similar to gut microbiome disruptions. For instance, studies show decreased alpha diversity (species richness) post-treatment, with overgrowth of opportunistic pathogens like Pseudomonas aeruginosa or antibiotic-resistant strains. In CRS patients, antibiotics during acute exacerbations shift the bacterial community, often without resolving symptoms, as the microbiome fails to rebound quickly. By eliminating protective commensals, antibiotics create ecological niches for pathogens or secondary invaders, potentially worsening CRS or leading to recurrent infections. For example, depletion of Corynebacterium spp. reduces inhibition of S. aureus, a common CRS pathogen. Broad-spectrum use fosters antibiotic-resistant bacteria within the microbiome, complicating future treatments. Repeated courses, combined with steroids (which further suppress immunity), pollution, or allergens amplify disruptions. Evidence suggests limited symptomatic benefit from systemic antibiotics in CRS, questioning their routine use given the microbiome harm. This non-selectivity underscores the need for targeted therapies, to preserve commensals.

[0063] Currently, antifungals are used for fungal rhinosinusitis, including allergic fungal rhinosinusitis (AFRS) or invasive forms, with agents like amphotericin B (topical irrigations), azoles (e.g., itraconazole, voriconazole), or echinocandins. These target pathogenic fungi such Aspergillus oxMucor spp., but their broad action affects the sinonasal mycobiome — the fungal component — including commensals \ Malassezia spp., Alternaria, and Cladosporium. Commensal fungi contribute to immune tolerance and bacterial -fungal interactions, preventing overgrowth of harmful species. Currently used antifungals reduce pathogenic loads but also deplete beneficial fungi, altering compositions in CRS patients. For example, in AFRS, modulation decreases pathogens but risks overall fungal diversity loss, potentially exacerbating inflammation via bacterial -fungal imbalances (e.g., Aspergillus interacting with S. aureus biofilms). Interestingly, antibiotics (often coprescribed) variably increase fungal loads by reducing bacterial competitors, promoting fungal overgrowth and complicating antifungal efficacy. Aggressive antifungals like amphotericin can cause severe mucosal irritation while non-selectively clearing the my cobiome.

[0064] Antivirals for sinonasal viral infections (e.g., oseltamivir for influenza, remdesivir for certain coronaviruses) are more specific, targeting viral enzymes or replication in eukaryotic viruses like rhinovirus or influenza. The nasal virome includes commensal bacteriophages (viruses infecting bacteria) and eukaryotic viruses that may asymptomatically persist, aiding bacterial regulation and immune priming. Most antivirals (e.g., neuraminidase inhibitors) do not affect bacteriophages or commensal eukaryotic viruses, as they target specific pathogenic strains. Studies show no significant virome disruption, though viral infections themselves can alter the microbiome indirectly. Antivirals may prevent bacterial superinfections by resolving viral triggers, but if combined with antibiotics, the latter’s effects dominate.

[0065] In summary, the broad-spectrum nature of currently used antibiotics and antifungals, which prioritize rapid pathogen clearance over microbiome preservation, leading to dysbiosis and clinical challenges.

[0066] Commensal bacteria in human nasal passages, sinuses, or both, are microorganisms that typically coexist harmlessly with the host, often providing protective functions. They are integral to maintaining nasal health, preventing colonization by pathogenic microorganisms, and modulating immune responses. The human nasal cavity and sinuses host a diverse array of commensal bacteria, primarily from phyla such as Actinobacteria, Firmicutes, and Proteobacteria. For example, in some embodiments, commensal bacteria can include, without limitation, one or more of the following: Acinetobacter spp. (e.g., A. junii, A. indicus), Acidocella spp., Aeromonas spp., Aggregatibacter spp., Alicycliphilus spp., Asticcacaulis spp., Bradyrhizobium spp., Chryseobacterium spp., Citrobacter spp., Cloacibacterium spp., Clostridium spp., Coprobacillus spp. Corynebacterium spp. (e.g., C. accolens, C. amycolatum, C. aurimucosum, C. propinquum, C. pseudodiphtheriticum, C. segmentosum, C. striatum, C. tuberculostearicum), Cutibacterium spp. (e.g., C. acnes), Diaphorobacter spp., Dolosigranulum spp. (e.g., D. pigrum), Elizabethkingia spp. (e.g., E. anopheles), Enterobacter spp., Escherichia spp., Exiguobacterium spp., Flavobacterium spp., Fusobacterium spp., Haemophilus spp. (e.g., H. influenzae), Helicobacter spp., Hyphomicrobiaceae (family), Klebsiella spp., Lactobacillus spp. (e g-, L. sakei), Lawsonella spp., Leptotrichia spp., Micrococcus spp. (e.g., AL luteus), Moraxella spp. (e.g., AL catarrhalis), Neisseria spp. (e.g., TV. subflava, N. flavescens), Paenibacillus spp., Pedobacter spp., Peptoniphilus spp., Prevotella spp. (e.g., P. melaninogenica), Propionib acterium spp. (e.g., P. acnes, P. avidum, P. granulosum), Pseudoalteromonas spp., Pseudomonas spp. (e.g., P. aeruginosa, P. oleovorans), Ralstonia spp. (e.g., R. pickettii), Rheinheimera spp., Shewanella spp., Sphingobacterium spp., Staphylococcus spp. (e.g., S. aureus, S. capitis, S. epidermidis, S. hominis, S. lugdunensis), Stenotrophomonas spp. (e.g., S. maltophilia), Streptococcus spp. (e.g., S. mitis, S. parasanguinis, S. pneumoniae, S. pyogenes, S. salivarius), Streptomyces spp., Veillonella spp. (e.g., V. atypica, V. dispar, V. parvula), and Vibrio spp.

[0067] Fungi are less abundant than bacteria in the nasal microbiome but contribute to the commensal community, often dominated by species adapted to mucosal environments. For example, in some embodiments, commensal fungi can include, without limitation, one or more of the following: Altemaria spp. (e.g., A. alternata, A. breviramosa),

[0068] Aspergillus spp. (e.g., A. fumigatus, A. penicillioides), Aureobasidium spp. (e.g., A. pullulans), Bipolaris spp. (e.g., B. papendorfii), Cladosporium spp. (e.g., C. cladosporioides, C. delicatulum), Coniochaeta spp. (e.g., C. fasciculata), Cryptococcus spp. (e.g., C. neoformans), Fusarium spp., Malassezia spp. (e.g., AL globosa, M. restricta), Penicillium spp. (e.g., P. chrysogenum), Pleosporales (order), Rhodosporidium spp. (e.g., R. diabovatum), Saccharomyces spp., Scutellospora spp., and Trichosporon spp.

[0069] Viruses in the nasal microbiome often include bacteriophages (which target bacteria) and some eukaryotic viruses that persist asymptomatically. The virome is less well- characterized than the bacterial or fungal components, but certain viruses have been identified in healthy individuals. For example, in some embodiments, commensal viruses can include, without limitation, one or more of the following: Adenoviridae (family), Alphacoronavirus (genus), Anellovirus (genus), Betacoronavirus (genus), Cystovirus (genus) Enterovirus (genus), Herpesviridae (family), Klebsiella phages (various strains), Lambda-like viruses (genus), Myovirus (genus), N4-like viruses (genus), Papillomaviridae (family), Pseudomonas virus phi 12 (species), Rhinovirus (genus), Siphovirus (genus), and Tl-like viruses (genus). Pathogenic bacteria in the human nasal cavity and sinuses often include both aerobic and anaerobic species that can cause acute or chronic rhinosinusitis, particularly in susceptible individuals. Many of these are pathobionts, meaning they may reside as commensals but become pathogenic under conditions like immune compromise, viral co-infection, or structural abnormalities. For example, in some embodiments, the bacteria can include, without limitation, one or more of the following: Acinetobacter spp. (e.g., nosocomial), Bacteroides spp. (e.g., B. fragilis group; e.g., anaerobic, e.g., chronic sinusitis), Citrobacter spp. (e.g., Enterob acteriaceae, chronic), Cory neb acterium spp. (e.g., C. tuberculostearicunr, often in chronic sinusitis), Enterobacter spp. (e.g., Enterob acteriaceae, e.g., chronic / post-surgical), Enterococcus spp. (e.g., nosocomial, e.g., ventilator-associated), Escherichia coli (e.g., Enterob acteriaceae, e.g., chronic / post-surgical), Fusobacterium spp. (e.g., F. nucleatunr, e.g., anaerobic, e.g., chronic sinusitis), Haemophilus influenzae (e.g., acute / chronic sinusitis), Klebsiella spp. (e.g., K. pneumoniae, K. rhinoscleromatis e.g., causing rhinoscleroma; e.g., chronic / post-surgical), Moraxella catarrhalis (e.g., acute sinusitis), Mycobacterium spp. (e.g., M. tuberculosis e.g., causing tuberculosis, M. leprae e.g., causing leprosy), Peptostreptococcus spp. (e.g., anaerobic gram-positive cocci, e.g., chronic sinusitis), Porphyromonas spp. (e.g., anaerobic, e.g., chronic sinusitis), Prevotella spp. (e.g., anaerobic, e.g., chronic sinusitis; e.g., pigmented strains), Propionib acterium acnes (also known as Cutibacterium acnes) (e.g., anaerobic, e.g., chronic sinusitis), Proteus spp. (e.g., P. mirabilis,' e.g., nosocomial / chronic), Pseudomonas aeruginosa (e.g., nosocomial, e.g., chronic in cystic fibrosis / immunocompromised), Serratia marcescens (e.g., nosocomial), Staphylococcus spp. (e.g., S. aureus incl. e.g., MRSA, S. epidermidis as coagulasenegative; e.g., chronic / acute sinusitis), and Streptococcus spp. (e.g., S. pneumoniae, S. pyogenes, e.g., a-hemolytic streptococci; e.g., acute / chronic sinusitis).

[0070] Fungal pathogens are less common but can cause noninvasive (e.g., allergic fungal sinusitis, fungus ball) or invasive fungal rhinosinusitis, especially in immunocompromised hosts. Dematiaceous (dark-pigmented) molds are frequent in allergic forms, while zygomycetes like Mucor cause aggressive infections. For example, in some embodiments, the fungi can include, without limitation, one or more of the following: Alternaria spp. (e.g., chronic invasive, e.g., allergic), Apiospermum spp., Aspergillus spp. (e.g., A. fumigatus, A. flavus, A. niger, e.g., noninvasive / invasive), Bipolaris spp. (e.g., allergic, invasive), Blastomyces dermatitidis, Candida spp. (e.g., chronic invasive), Chrysosporium spp. (e.g., allergic), Cladosporium spp., Coccidioides spp., Cryptococcus neoformans, Curvularia spp. (e.g., C. lunata, e.g., allergic, invasive), Drechslera spp. (e.g., saprophytic, allergic), Emericella nidulans, Exserohilum spp. (e.g., saprophytic, allergic), Histoplasma spp., Mucor spp. (Mucorales order; e.g., invasive, allergic), Myriodontium keratinophilum, Paecilomyces spp., Paracoccidioides spp., Penicillium melinii, Pseudallescheria boydii, Rhizopus spp. (e.g., invasive), Scedosporium spp. (e.g., Monosporium), Schizophyllum commune, and Sporothrix schenckii (e.g., chronic invasive).

[0071] Viruses are primary causes of acute rhinosinusitis, often preceding bacterial superinfections. They are typically detected during upper respiratory infections that involve the nasal cavity and sinuses. For example, in some embodiments, the viruses can include, without limitation, one or more of the following: Adenovirus, Coronavirus, Cytomegalovirus (CMV) (in immunocompromised), Echovirus, Human metapneumovirus (HMPV), Influenza virus, Parainfluenza virus, and Rhinovirus.

[0072] The term “pathogenic” as used herein with regard to bacteria, fungi, or viruses in nasal passages, sinuses, or both, refers to the ability of these microorganisms to cause disease in animals, such as humans. This includes microorganisms that are inherently capable of causing infections or diseases, as well as those that are opportunistic, meaning they can lead to illness under specific conditions, such as when the host’s immune system is weakened. As discussed above, while many microorganisms in the nasal passages, sinuses, or both, are harmless or even beneficial as part of the normal flora, pathogenic bacteria, fungi, or viruses in the nasal passages, sinuses, or both, have the potential to disrupt health, either locally in the nasal passages, sinuses, or both, or elsewhere in the body. Some commensal microorganisms, which typically coexist harmlessly with the host, can become pathogenic under specific conditions, such as immune suppression or microbial imbalance, as discussed herein.

[0073] Accordingly, in some embodiments, the present disclosure relates to a composition for use in preventing or treating an infection in the nasal passages, sinuses, or both, of a subject, the composition comprising an amount of one or more peptoid compounds effective to prevent or treat the infection of the nasal passages, sinuses, or both.

[0074] In some embodiments, the peptoid compounds and compositions thereof described herein have improved activity compared to existing antibiotics, antifungals, antivirals, or combinations thereof, and improved selectivity against nasal pathogens, while having relatively little or no activity against commensal bacteria, fungi, or viruses. For instance, Example 4 shows example, non-limiting experimental data relating to an example peptoid, MXB-22,510, that selectively kills Methicillin-resistant Staphylococcus aureus (MRSA) and Candida albicans in a nonhuman primate study, while sparing commensal Staphylococcus. The peptoids described herein can be formulated or co-formulated in a variety of dosage forms for administration to a subject’s nasal passages, sinuses, or both.

[0075] The terms “peptoid” or “peptoid compound” as used herein refers to a type of biomimetic molecule that is similar to peptides but differs in its structure. Peptoids are synthetic oligomers composed of N-substituted glycine units. Accordingly, peptoids are also known as poly-N-substituted glycine compounds. In contrast to peptides, which have a peptide bond between amino acids, peptoids have a N-substituted (or N-alkylated) amide bond. This structural difference gives peptoids unique properties compared to peptides. Peptoids can be designed and synthesized to mimic the functions of natural peptides but with enhanced stability and different chemical properties. Peptoid compounds may be cyclic or linear. Peptoids have been described, for example, in U.S. Pat. No. 8,445,632, U.S. Pat. No. 8,828,413, U.S. Pat. No. 9,315,548, U.S. Pat. No. 9,872,495, U.S. Pat. No. 9,938,321, and International Patent Application Publication No.’s WO2021046562, WO2020223581, WO2021127294, WO2023287570, WO2022120393, and WO2021231343, the disclosures of which are incorporated herein by reference in their entireties.

[0076] For example, without limitation, in some embodiments a peptoid compound may have a formula:

[0077] In such a compound, A can be selected from H and a terminal N-alkyl substituted glycine residue, where such an alkyl substituent can be selected from about C4 to about C20 linear, branched and cyclic alkyl moi eties; n can be an integer selected from 1-3; B can be selected from NH2, and one and two N-substituted glycine residues, such N- substituents as can be independently selected from a-amino acid side chain moieties and structural / functional analogs thereof; and X, Y and Z can also be independently selected from N-substituted glycine residues, such N-substituents as can be independently selected from a-amino acid side chain moieties and structural / functional analogs thereof and proline residues. Such X-Y-Z periodicity can provide such a compound a certain amphipathicity. As would be understood by those skilled in the art, such structural and / or functional analogy can be considered in the context of any such a-amino acid side chain, N-substituent and / or a sequence of such N-substituted glycine residues, such structure and / or function including but not limited to charge, chirality, hydrophobicity, amphipathicity, helical structure and facial organization. Such analogs include, without limitation, carbon homologs of such side chain — such homologs as would be understood in the art, including but not limited to plus or minus 1 or 2 or more methylene and / or methyl groups.

[0078] A can be H, and B can be selected from one or two N-substituted glycine residues, such a selection as can reduce the hydrophobicity of such a compound, as compared to compounds of 3-fold periodicity. In certain such embodiments, X can be an NLys residue; n can be 2-3; and B can be two N-substituted glycine residues. Without limitation, such a compound can be of a formula:

[0079] Regardless of identity of A, X and B, at least one of Y and Z can be a proline residue. X, Y and Z can be proline residues.

[0080] In certain other embodiments, A can be a terminal N-alkyl substituted glycine residue, with such an alkyl substituent as can be selected from about C6 to about C18 linear alkyl moieties. Regardless, B can be NH2, and n can be selected from 1 and 2. In certain such embodiments, A can be a terminal N-alkyl substituted glycine residue, with an alkyl substituent selected from about C6 to about C18 linear alkyl moieties. Regardless, B can be an NLys residue, and n can be 1.

[0081] In some embodiments, a peptoid compound may have a formula: wherein n can be selected from 2 and 3; and Y, Z, Y' and Z' can be independently selected from N-substituted glycine residues, where such substituents can be independently selected from a- amino acid side chain moieties and carbon homologs thereof. Such Y' and Z' residues can be selected to provide such compound reduced hydrophobicity as compared to a compound of 3- fold periodicity. In certain such embodiments, at least one of X and Y can be a proline residue. Regardless, n can be selected from 2 and 3, and Y' can be an NLys residue. In certain such embodiments, one or both X and Y can be proline residues. Without limitation, such a compound with reduced hydrophobicity can be of a formula:

[0082] In some embodiments, a peptoid compound may have a formula: wherein B can be selected from NH2 and X'; X, Y, Z and X' can be independently selected from N-substituted glycine residues, where such substituents can be independently selected from a- amino acid side chain moieties and carbon homologs thereof; n can be an integer selected from 1 and 2; and R can be an N-alkyl substituent of such a glycine residue, as can be selected from about C4to about C20 linear, branched and cyclic alkyl moieties. In some embodiments, n can be 2, and B can be NH2. In some embodiments, n can be 1, and B can be X'. Accordingly, one or both of X and X' can be N ys residues. Regardless, an alkyl substituent can be selected from about Ceto about Cis linear, branched and cyclic alkyl moieties, and X and X' can be N ys residues. Without limitation, such a compound can be of a formula:

[0083] H - N tri dec - N Ly s - spe - spe - Ly s - NH2.

[0084] A peptoid may be a poly-N-substituted glycine compound comprising an N-terminus selected from H and an N-alkyl substituted glycine residue, where such an alkyl substituent can be selected from about C4 to about C20 linear, branched and cyclic alkyl moieties; a C-terminus selected from NH2, one and two N-substituted glycine residues, such N- substituents as can be independently selected from a-amino acid side chain moieties and structural / functional analogs thereof; and 2 to about 15 monomeric residues between the N- and C-termini, each such residue as can be independently selected from proline residues and N-substituted glycine residues, said N-substituents independently selected from a-amino acid side chain moieties and structural / functional analogs thereof. Such monomers can be selected to provide such a compound a non-periodic sequence of monomers. As would be understood by those skilled in the art, such structural and / or functional analogy can be considered in the context of any such a-amino acid side chain, N-substituent and / or a sequence of such N-substituted glycine residues, such structure and / or function including but not limited to charge, chirality, hydrophobicity, amphipathicity, helical structure and facial organization. Such analogs include, without limitation, carbon homologs of such side chain — such homologs as would be understood by those skilled in the art, including but not limited to plus or minus 1 or 2 or more methylene and / or methyl groups.

[0085] The N-terminus of such a compound can be H; and the C-terminus can be selected from said one and two N-substituted glycine residues. A peptoid compound can comprise 2 to about 5 (X-Y-Z) non-periodic trimers. At least one of X, Y and Z in each of the trimers can be selected to interrupt 3-fold periodicity. Without limitation, at least one X in at least one said trimer can be an NLys residue. At least one of Y and Z in at least one such trimer can be a proline residue. The monomeric residues can comprise at least two non-consecutive of the same or repeat trimers, with at least one such residue therebetween to interrupt periodicity. At least one X in at least one such trimer can be an NLys residue, and at least one of Y and Z in at least one said trimer can be a proline residue.

[0086] The N-terminus of such a compound can be an N-alkyl substituted glycine residue, with an alkyl substituent selected from about C6 to about C18 linear alkyl moi eties. A peptoid compound can comprise 2 to about 5 (X-Y-Z) non-periodic trimers. At least one of X, Y and Z in each of the trimers can be selected to interrupt 3-fold periodicity. The monomeric residues can comprise at least two non-consecutive of the same or repeat trimers, with at least one residue therebetween to interrupt periodicity. At least one X in at least one said trimer can be an NLys residue, and at least one of Y and Z in at least one said trimer can be a proline residue.

[0087] Various halogenated peptoids may be utilized in accordance with the teachings herein to make antiviral pharmaceutical compositions and treatments. These include, without limitation, various halogenated analogs of the foregoing peptoid compounds. These halogenated compositions may be halogenated in various ways. For example, these compounds may include any number of halogen substitutions with the same or different halogens. In particular, these compounds may include one or more fluoro-, chloro-, bromo- or iodosubstitutions, and may include substitution with two or more distinct halogens. In some embodiments, the use of one or two bromo- or chloro-substitutions may be used. The peptoids described herein may be halogenated at various locations, for example and without limitation para halogenation on the peptoids containing aryl rings, ortho- and meta-substitution, or perhalogenation.

[0088] The peptoids described herein may be alkylated, for example and without limitation terminal alkylation. For example and without limitation, the alkyl substituent may be selected from about Ce to about Cis linear alkyl moieties.

[0089] In some embodiments, a peptoid may have activity against pathogenic bacteria, pathogenic fungi, pathogenic viruses, or any combination thereof.

[0090] Accordingly, in some embodiments, the term “pathogen” as used herein refers to any non-commensal virus, non-commensal bacterium, or non-commensal fungus. These pathogens can disrupt the normal function of the nasal passages, sinuses, or both, leading to various infections and conditions. A pathogen that causes infections in in the nasal passages, sinuses, or both, of a subject is also understood to refer to any microorganism or agent that is associated with a disease or pathologic condition of the nasal passages, sinuses, or both, such as those described herein.

[0091] For example, in some embodiments, pathogens can include bacteria such as, without limitation, one or more of the following. Staphylococcus aureus, Streptococcus pyogenes, Propionibacterium acnes, Pseudomonas aeruginosa, Mycobacterium marinum, Corynebacterium species e.g., Corynebacterium minutissimum, Corynebacterium tenuis, Corynebacterium jeikeium, Corynebacterium striatum, and Corynebacterium amycolatum, Propionibacterium acnes also known as Cutibacterium acnes, Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible Staphylococcus aureus (MS SA), Staphylococcus epidermis, Staphylococcus warneri, Staphylococcus mitis, Acinetobacter johnsonii, coagulase-negative staphylococci, Mycobacterium marinum, Pseudomonas aeruginosa, Streptococcus pyogenes, Corynebacterium minutissimum, Corynebacterium tenuis, Corynebacterium jeikeium, Corynebacterium striatum, Corynebacterium amycolatum, Enterobacter species (spp.), Klebsiella spp., Escherichia coli, o Proteus spp., among others.

[0092] In some embodiments, the pathogenic bacteria may include but is not limited to Staphylococcus spp., e.g. Staphylococcus aureus, Staphylococcus epidermidis; Enterococcus spp., e.g. Enterococcus faecalis; Klebsiella spp., e.g. Klebsiella pneumoniae; Acinetobacter spp., e.g. Acinetobacter baumannii; Pseudomonas spp., e.g. Pseudomonas aeruginosa; Enterobacter spp.; Streptococcus pyogenes; Listeria spp.; Pseudomonas spp.; Mycobacterium spp., e.g. Mycobacterium tuberculosis; Enterobacter spp.; Campylobacter spp.; Salmonella spp.; Streptococcus spp., e.g. Streptococcus Group A or B, Streptoccocus pneumoniae; Helicobacter spp., e.g. Helicobacter pylori; Neisseria spp., e.g. Neisseria gonorrhea, Neisseria meningitidis; Borrelia burgdorferi; Shigella spp., e.g. Shigella flexneri; Escherichia coli; Haemophilus spp., e.g. Haemophilus influenzae; Chlamydia spp., e.g. Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci; Francisella fularensis; Bacillus spp., e.g. Bacillus anthracis; Clostridia spp., e.g. Clostridium botulinum; Yersinia spp., e.g. Yersinia pestis; Treponema spp.; Burkholderia spp.; e.g. Burkholderia mallei and B pseudomallei, or the combination thereof. In some embodiments, the infection is from one of the ESKAPE pathogens including Enterococcus spp., e.g. Enterococcus faecalis; Staphylococcus spp., e.g. Staphylococcus aureus, Staphylococcus epidermidis; Klebsiella spp., e.g. Klebsiella pneumoniae; Acinetobacter spp., e.g. Acinetobacter baumannii; Pseudomonas spp., e.g. Pseudomonas aeruginosa; Enterobacter spp., or the combination thereof. Also in some embodiments,, the bacteria are selected from Acidothermus cellulyticus, Actinomyces odontolyticus, Alkaliphilus metalliredigens, Alkaliphilus oremlandii, Arthrobacter aurescens, Bacillus amyloliquefaciens, Bacillus clausii, Bacillus halodurans, Bacillus licheniformis, Bacillus pumilus, Bacillus subtilis, Bifidobacterium adolescentis, Bifidiobacterium longum, Caldicellulosiruptor saccharolyticus, Carboxydothermus hydrogenoformans, Clostridium acetobutylicum, Clostridium beijerinckii, Clostridium botulinum, Clostridium cellulolyticum, Clostridium difficile, Clostridium kluyveri, Clostridium leptum, Clostridium novyi, Clostridium perfringens, Clostridium tetani, Clostridium thermocellum, Corynebacterium diphtheriae, Corynebacterium efficiens, Corynebacterium glutamicum, Corynebacterium jeikeium, Corynebacterium urealyticum, Desulfitobacterium hafniense, Desulfotomaculum reducens, Eubacterium ventriosum, Exiguobacterium sibiricum, Finegoldia magna, Geobacillus kaustophilus, Geobacillus thermodenitrificans, Janibacter sp., Kineococcus radiotolerans, Lactobacillus fermentum, Listeria monocytogenes, Listeria innocua, Listeria welshimeri, Moorella thermoacetica, Mycobacterium avium, Mycobacterium bovis, Mycobacterium gilvum, Mycobacterium leprae, Mycobacterium paratuberculosis, Mycobacterium smegmatis, Mycobacterium tuberculosis, Mycobacterium ulcerans, Mycobacterium vanbaalenii, Nocar dioides sp., Nocardia farcinica, Oceanobacillus iheyensis, Pelotomaculum the rmopropionicum, Rhodococcus sp., Saccharopolyspora erythraea, coagulase-negative Staphylococcus species, Staphylococcus aureus, methicillin resistant Staphylococcus aureus (MRS A), Staphylococcus epidermidis, methicillin resistant Staphylococcus epidermidis, (MRSE), Staphylococcus pseudintermedius, Staphylococcus intermedins, Staphylococcus delphini, Streptococcus agalactiae, Streptococcus gordonii, Streptococcus mitis, Streptococcus oralis, Streptococcus pneumoniae, Streptococcus sanguinis, Streptococcus suis, Streptomyces avermitilis, Streptomyces coelicolor, Thermoanaerobacter ethanolicus, Thermoanaerobacter tengcongensis, or any combinations thereof.

[0093] As another example, in some embodiments, pathogens include fungi such as the following, without limitation. Trichophyton species, such as Trichophyton rubrum, Epidermophyton species, such as Epidermophyton floccosum, Candida species, such as Candida albicans, Microsporum canis, Malassezia furfur Sporothrix schenckii, Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum, Candida spp., including Candida albicans, Candida parapsilosis, and Candida auris, Microsporum canis, Microsporum audouinii, Epidermophyton floccosum, Malassezia furfur, Malassezia globosa, Sporothrix schenckii, Sporothrix schenckii, Fonsecaeaspp., Cladophialophora spp., Exophiala spp., Basidiobolus ranarum, Conidiobolus spp., Aspergillus fumigatus, Fusarium spp., among others.

[0094] In some embodiments, the pathogenic virus may include, but is not limited to, Herpes Simplex Virus 1 (HSV-1), Herpes Simplex Virus 2 (HSV-2), Varicella-Zoster Virus (VZV), Human Papillomavirus (HPV), Molluscum Contagiosum Virus (MCV), Parvovirus Bl 9, Coxsackievirus, Human Herpesvirus 6 (HHV-6), Human Herpesvirus 7 (HHV-7), Epstein-Barr Virus (EBV), Cytomegalovirus (CMV), Variola virus (smallpox), Vaccinia virus, Monkeypox virus (MPox), Measles virus, Rubella virus, Enteroviruses, including Coxsackievirus and Enterovirus 71, Arboviruses, including Dengue virus, Chikungunya, and West Nile virus, or Human Immunodeficiency virus (HIV) among others.

[0095] Without intending to be bound by theory, the peptoid compounds described herein mimic the structures and functions of antimicrobial peptides, key constituents of the human immune system, to exert broad direct antibacterial, antiviral and antifungal activity. Peptoids are structural variants of peptides, in which the side chain groups are appended to nitrogen (instead of carbon) to form an amphiphilic molecule with both hydrophobic and cationic features. This novel structure resists proteolysis to form a more stable compound in vivo with the same anti-pathogenic properties as natural peptides.

[0096] Without intending to be bound by theory, antiviral activity of a peptoid may be associated with its ability to pass through a viral membrane and to bind to viral DNA or RNA. Furthermore, also without intending to be bound by theory, the mechanism of action may also feature disruption of membranes of various pathogens, by preferentially interacting with the lipid phosphatidylserine, which is found on the outer leaflet of various pathogen membranes. Phosphatidylserine is not typically present on mammalian cell surfaces, allowing peptoid compounds to exhibit selectivity towards microbial cell types. The peptoid compounds described herein offer substantial pharmacological advantages over monoclonal antibodies and biological therapeutics: smaller size, low risk of off target effects, low manufacturing cost, antiinflammatory properties, no cold chain requirement, high stability in vivo, and multiple mechanisms of action.

[0097] Various peptoid compounds may be utilized in accordance with the teachings herein to make pharmaceutical compositions and treatments, including without limitation the peptoid compounds described in the various patents and patent application publications described herein, which are incorporated herein in their entireties.

[0098] The peptoids described herein may be synthesized and provided by any suitable method known in the art, such as, for example and not by way of limitation, the method described in Example 1 of the present disclosure, or by methods described in the patents and patent application publications disclosed herein.

[0099] Various counterions may be utilized in forming pharmaceutically acceptable salts of the peptoids disclosed herein. In some embodiments, pharmaceutically acceptable salts of the peptoids disclosed herein may include sodium or hydrochloride salts.

[0100] In some embodiments, the present disclosure extends to the preparation of prodrugs and derivatives of the peptoids of the invention. Prodrugs are derivatives which have cleavable groups and become by solvolysis or under physiological conditions the peptoid of the invention, which are pharmaceutically active. Such examples include, but are not limited to, choline ester derivatives and the like, N-alkylmorpholine esters and the like. In some embodiments, the peptoid compounds provided herein may be prepared e.g., in crystalline form and may be solvated or hydrated. Suitable solvates include pharmaceutically acceptable solvates, such as hydrates, and further include both stoichiometric solvates and non- stoichiometric solvates.

[0101] In some embodiments, the present disclosure relates to a composition for use in preventing or treating a pathogen infection in nasal passages, sinuses, or both, of a subject, the composition comprising one or more peptoids described herein. In some embodiments, the peptoid may be one or more of the peptoids described in Table 1 in the Examples of the present disclosure, including but not limited to peptoid compounds referred to herein as MXB-24,656, MXB-22,510, MXB-27,369, MXB-25,605, MXB-24,816, and MXB-25,739.

[0102] In some embodiments, the peptoid may be one or more of the peptoid compounds referred to herein as MXB-22,510, MXB-24,816, and MXB-27,369.

[0103] It has been surprisingly found that not all peptoid compounds may be suitable for use as agents for use in treating or preventing infections of nasal passages, sinuses, or both, that selectively inhibit pathogens while relatively sparing the commensal microbiome. In some embodiments, one or more of the peptoid compounds referred to herein as MXB-22,510, MXB- 24,816, and MXB-27,369 may be administered to nasal passages, sinuses, or both, of a subject to selectively prevent or treat a pathogenic infection of nasal passages, sinuses, or both, while relatively sparing the commensal microbiome of the nasal passages, sinuses, or both.

[0104] In some embodiments, the present disclosure provides a method of decolonizing a microbial organism comprising contacting the microbial organism separately or simultaneously with one or more of the peptoid compounds referred to herein as MXB-22,510, MXB-24,816, and / or MXB-27,369 as may be administered to the nasal passages, sinuses, or both, of a subj ect to selectively prevent or treat a pathogenic / topical infection of nasal passages, sinuses, or both, while relatively sparing the commensal microbiome. The topical infection is an infection on a surface or localized region of a subject including skin, eye, a mucus membrane, the surface of a cavity such as the nasal passages, sinuses, or both, etc.

[0105] Activity of the one or more peptoid compounds against one or more pathogens of the nasal passages, sinuses, or both, or one or more commensal bacteria, or fungi, may be tested using methods known in the art, such as the following, without limitation. As described in Example 3, a non-human primate model of a pathogenic methicillin-resistant S. aureus BAA- 1717 (MRS A) nasal colonization was used to evaluate the antimicrobial efficacy of MXB- 22,510 when administered to the colonized epithelium of the nasal cavity. To do so, the nasal cavity of rhesus macaque monkeys were inoculated with MRSA then treated twice a day for 10 days, at which point the bacterial burden was measured by standard culture methods. In subjects where the bacterial load of MRSA BAA-1717 strain was at least 103, a 3 log reduction was observed following treatment with MXB-22,510 after 3 days. Similar results were observed for the treatment of Candida albicans strain 96901. Taken together, these results indicate MXB-22,510 possesses multi-kingdom antimicrobial effects. Based on these results, combined with the low resolution of the nasal models available, studies will be expanded to evaluate single and / or multiple peptoid effects on in vivo murine wound models of infection.

[0106] In some embodiments, the peptoid compound for use according to the methods described herein is referred to herein as “MXB-22,510”, having a sequence H-Ntridec-NLys- Nspe-Nspe-NLys-NEh, and having a molecular structure: In some embodiments, the peptoid compound for use according to the methods described herein is referred to herein as “MXB-24,816”, having a sequence H-Ntetradec-NLys- Nspe-Nspe-NLys-NH2, and having a molecular structure:

[0107] In some embodiments, the peptoid compound for use according to the methods described herein is referred to herein as “MXB-27,369” having a formula H-Ndec-Nlys- Nspe-Nspe(p-Br)-Nlys-Npse-Nspe(p-Br)-NH2, and having a molecular structure:

[0108] Advantageously, the peptoids described herein have healing properties, associated not only with their infection-fighting properties, but also including but not limited to the following. The peptoids are not immunogenic and so do not interfere with healing of nasal passages, sinuses, or both. Peptoids promote apoptosis of damaged cells and promote neutrophil engagement. Peptoids are also non-irritating, and do not require continued moistening. Furthermore, peptoids can be administered via various routes, as described herein.

[0109] In some embodiments, the peptoid compounds and compositions thereof described herein have activity to inhibit growth of one or more pathogens by up to 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100%.

[0110] In some embodiments, the peptoid compounds and compositions thereof described herein have activity to inhibit growth of one or more pathogens while inhibiting growth of a commensal bacteria species, a commensal fungal species, or a commensal virus species by no more than 99%, 90%, 75%, 66%, 50%, 40%, 30%, 20%, 10%, 5%, 2%, or 1%.

[0111] In some embodiments, the peptoid compounds and compositions thereof described herein have activity to inhibit growth of one or more pathogens while inhibiting growth of a commensal bacteria, fungi, or virus species, or any combination thereof by no more than a 2- log reduction. As skilled persons would understand, measuring log reduction inhibition of bacteria, fungi, or virus species in response to administration of a peptoid quantifies the effectiveness of the peptoid in reducing populations of the bacteria, fungi, or virus species. It involves comparing the number of viable microorganisms before and after treatment, expressed as a logarithmic reduction. A 1-log reduction equates to a 90% decrease, a 2-log reduction means a 99% decrease, and so on.

[0112] Activity of the one or more peptoid compounds against one or more pathogens or one or more commensal bacteria, fungi, or virus may be tested using methods known in the art, such as the following, without limitation.

[0113] Suitable assays for quantifying the activity of a compound against pathogenic bacteria or commensal bacteria may include the following, without limitation. Minimum Inhibitory Concentration (MIC) testing, in which MIC is the lowest concentration of a compound that inhibits visible bacterial growth. For example, MIC may be determined using broth microdilution, which includes serial dilutions of the compound in liquid media, followed by bacterial inoculation and incubation. Growth is assessed by turbidity or colorimetric indicators. MIC may be determined using agar dilution, in which a compound is incorporated into agar plates at different concentrations, and bacterial growth is monitored. Minimum Bactericidal Concentration (MBC) testing is the lowest concentration that kills 99.9% of bacteria. After MIC determination, samples from non-turbid wells are plated on fresh agar to check for bacterial survival. Disk diffusion (Kirby-Bauer) assay, in which a filter paper disk soaked with the compound is placed on an agar plate inoculated with bacteria. After incubation, the zone of inhibition (clear area around the disk) is measured to assess antimicrobial potency. Time-Kill Assay, in which bacteria are exposed to the compound at different concentrations, and samples are taken at various time points to determine bacterial survival by colony-forming unit (CFU) counting. Growth curve analysis, in which bacterial cultures are grown in the presence of the compound, and optical density (OD600) is measured over time to assess the impact on bacterial growth dynamics. Flow cytometry or fluorescence-based assays, such as live / dead staining, in which fluorescent dyes (e.g., propidium iodide) differentiate live and dead bacteria, or membrane potential dyes, which indicate bacterial membrane disruption by the compound. ATP bioluminescence assay, which measures bacterial metabolic activity by detecting ATP levels using luciferase-based luminescence. Electron Microscopy (SEM / TEM), which is used to visualize structural damage caused by the compound at the cellular level.

[0114] Quantifying the activity of a compound against fungi involves methods similar to antibacterial testing, with modifications suited for fungal physiology. Methods include the following, without limitation. MIC is the lowest concentration of a compound that inhibits visible fungal growth. One common method is broth microdilution (e.g., following CLSI or EUCAST guidelines), in which serial dilutions of the compound in liquid media, followed by fungal inoculation and incubation. Growth is assessed visually or using spectrophotometry (OD600 or OD530). Another common method is agar dilution, in which the compound is incorporated into agar at different concentrations, and fungal growth is observed. Minimum Fungicidal Concentration (MFC) testing is the lowest concentration that kills 99.9% of fungal cells. After MIC determination, samples from non-turbid wells are plated on fresh agar to assess fungal survival. Disk diffusion (Kirby-Bauer) assay in which a filter paper disk soaked with the compound is placed on an agar plate inoculated with fungi. The zone of inhibition (clear area around the disk) is measured to evaluate antifungal potency. Time-Kill assay in which fungal cultures are exposed to the compound at different concentrations, and samples are taken at various time points to determine survival by counting colony-forming units (CFU / mL). Growth curve analysis, in which fungal cultures are grown in the presence of the compound, and optical density (OD600 or OD530) is measured over time to track growth inhibition. Cell viability and membrane integrity assays, such as live / dead staining, such as those using fluorescent dyes e.g., propidium iodide and FUN-1 differentiate live from dead fungal cells. Membrane potential dyes, which assess changes in membrane integrity e.g., using DiBAC4(3) or DiSC3(5). ATP bioluminescence assay, which measures fungal metabolic activity by detecting ATP levels using luciferase-based luminescence. Ergosterol quantification in which e.g. HPLC or spectrophotometric assays can measure reductions in ergosterol levels as an indicator of antifungal activity. Ergosterol is a key component of fungal membranes. Hyphal growth and morphological analysis, which for filamentous fungi, microscopy is used to assess changes in hyphal structure, branching, and conidiation after compound exposure. Electron Microscopy (SEM / TEM) which is used to visualize ultrastructural damage in fungal cells after compound treatment.

[0115] Quantifying the activity of a compound against viruses involves assessing its ability to inhibit viral replication, prevent infection, or inactivate the virus. Methods include the following, without limitation. Plaque Reduction Assays (PRA) / Plaque Forming Unit (PFU) Assays are used for cytopathic viruses that form plaques in a monolayer of host cells. Methods of PRA or PFU assays may be performed as follows. Host cells are infected with the virus in the presence or absence of the compound. After incubation, an overlay (e.g., agar or methylcellulose) is applied to restrict viral spread. After a few days, plaques (clear zones) are counted. The reduction in plaque number compared to untreated controls indicates antiviral efficacy. TCID so (Median Tissue Culture Infectious Dose) assays determine the concentration of virus that infects 50% of cell cultures and may be performed as follows. Serial dilutions of the virus are added to host cells in the presence of the compound. After incubation, cytopathic effects (CPE) are observed. The TCIDso is calculated using statistical methods (e.g., Reed- Muench or Spearman-Karber). A reduction in TCIDso indicates antiviral activity. Viral yield reduction assay measures the total amount of infectious virus produced after treatment and may be performed as follows. Host cells are infected with the virus and treated with the compound. After incubation, viral particles in the supernatant are collected. Virus titers are determined using plaque assays, TCIDso, or quantitative PCR (qPCR). A decrease in viral yield compared to untreated controls indicates antiviral potency. qPCR / RT-qPCR (Quantitative PCR / Reverse Transcription qPCR) measures viral RNA or DNA levels and may be performed as follows. Cells are infected with the virus and treated with the compound. RNA / DNA is extracted from viral particles or infected cells. qPCR is performed using virus-specific primers. A decrease in viral genome copies indicates inhibition of replication. Immunofluorescence / ELISA (Enzyme-Linked Immunosorbent Assay) detects viral proteins in infected cells and may be performed as follows. Cells are infected and treated with the compound. After incubation, viral proteins are stained with specific antibodies. Detection is done via fluorescence microscopy (immunofluorescence) or colorimetric detection (ELISA). A decrease in viral protein levels indicates antiviral activity. Reporter Virus assays uses genetically engineered viruses with fluorescent (e.g., GFP) or luminescent (e.g., luciferase) markers and may be performed as follows. Cells are infected with a reporter virus and treated with the compound. Viral replication is measured by fluorescence or luminescence. A decrease in signal indicates inhibition of viral replication. Direct virus inactivation assay determines if the compound directly inactivates viral particles and may be performed as follows. The virus is pre-incubated with the compound. Treated virus is then used to infect host cells. Viral titers (e.g., via plaque assay) are compared to untreated controls. A reduction in infectivity suggests direct virucidal action. Single-round infection assays are used for viruses engineered to complete only one round of infection. Cells are infected with a replication-deficient virus expressing a reporter (e.g., luciferase). The compound is added, and infection is measured by luminescence or fluorescence.

[0116] In some embodiments, the present disclosure relates to the use of the broad-spectrum anti-pathogenic peptoids described herein to treat or prevent a wide array of pathogen infections in a pathogen-agnostic manner. Because of the broad-spectrum, pathogen-agnostic, activity of the peptoids, in some embodiments, the infection may be an infection of an unidentified pathogen at the time of administering the composition. In some embodiments, the composition of the present disclosure is adapted for administering to a subject for preventing or treating an infection in the subject, prior to identifying, or confirming the identity of, the pathogen, or the presence of a pathogen, in the nasal passages, sinuses, or both, of the subject. In some embodiments, the infection may be an infection of one or more unidentified or unconfirmed pathogenic bacteria, fungi, or viruses, or any combinations thereof.

[0117] The one or more peptoids may be effective in simultaneously treating infections involving the one or more pathogens, including but not limited to one or more pathogenic bacteria, fungi, viruses, or any combinations thereof.

[0118] In some embodiments, the one or more pathogens may show multi-drug-resistant properties.

[0119] In some embodiments, the bacterial infection may be an infection of one or more types of bacteria. For example, and without limitation, the bacteria may be selected from Propionibacterium acnes. Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRS A) methicillin-susceptible Staphylococcus aureus (MS SA), coagulase-negative staphylococci, Mycobacterium marinum, Pseudomonas aeruginosa, Streptococcus pyogenes, Corynebacterium minutissimum, Corynebacterium tenuis, Corynebacterium jeikeium, Corynebacterium striatum, and Corynebacterium amycolatum, and any combinations thereof.

[0120] In some embodiments, the fungal infection may be an infection of one or more types of fungi. For example, and without limitation, the fungal infection may be an infection of a pathogen selected from Trichophyton rubrum, Epidermophyton floccosum, Candida albicans, Microsporum canis, Malassezia furfur, Sporothrix schenckii, and any combinations thereof.

[0121] In some embodiments, the viral infection may be an infection of one or more types of viruses. For example, and without limitation, the viral infection may be an infection of a pathogen selected from Herpes Simplex Virus 1, Herpes Simplex Virus 2, Varicella-Zoster Virus (VZV), Human Papillomavirus (HPV), Molluscum Contagiosum Virus (MCV), Parvovirus Bl 9, Coxsackievirus, Human Herpesvirus 6 (HHV-6), and any combinations thereof.

[0122] In some embodiments, the composition of the present disclosure may comprise an amount of the one or more peptoid compounds described herein effective to prevent, decrease, or inhibit a biofilm.

[0123] In some embodiments, the composition of the present disclosure may comprise an amount of the one or more peptoid compounds described herein effective to prevent, decrease, or inhibit an infection of a pathogen in the nasal passages, sinuses, or both, of a subject.

[0124] In some embodiments, the composition may be formulated for administration via one or more routes to the subject, in order to treat the infection. In some embodiments, the composition may be formulated for intranasal administration to the subject.

[0125] Intranasal (IN) medication administration is a non-invasive route for delivering drugs through the nasal cavity. For example, and not by way of limitation, intranasal administration can be performed using one or more of the following methods: Dripping (direct instillation) involves dripping medication slowly into the nares, e.g., using a syringe, allowing absorption time between drops. Nasal sprays may be used, e.g. delivered via pump bottles or metered-dose sprays for mist distribution. Atomization uses mucosal atomization devices (MAD) to create a fine mist (30-100 microns), covering a larger surface area for better absorption. Nebulization involves aerosolization of medication for inhalation. Powder insufflation involves snorting solid formulations as powder. In some embodiments, the peptoids may be formulated in suitable intranasal preparations such as, without limitation, gels, nanoparticles (e.g., liposomes, chitosan-based), or penetration enhancers to prolong residence and enhance permeability.

[0126] In some embodiments, the present disclosure relates to a composition comprising one or more peptoid compounds described herein and one or more pharmaceutically acceptable excipients.

[0127] Accordingly, in some embodiments, the peptoid compounds of the present disclosure may be formulated in a composition suitable for administration to the subject via various routes to treat or prevent the infection. Such compositions can be prepared in a manner known in the pharmaceutical art. The peptoid compounds described herein can be formulated into pharmaceutically acceptable compositions and dosage forms for administration to a subject. In some embodiments, the present disclosure relates to a composition comprising an effective amount of a peptoid compound described herein for use in a method of treating a subject for an infection of the nasal passages, sinuses, or both. In some embodiments, the present disclosure relates to the use of the peptoids described herein for the preparation of medicaments or as medicaments, that may be used for treating an infection of the nasal passages, sinuses, or both, in a subject.

[0128] The present disclosure provides pharmaceutical compositions comprising one or more peptoids and a pharmaceutically acceptable medium, such as an excipient, carrier, or the like. The peptoids described herein may be dissolved, suspended or dispersed in various media. Such media may include, for example, various liquid, solid or multistate media such as, for example, emulsions, gels or creams. Such media may include liquid media, which may be hydrophobic or may comprise one or more triglycerides or oils. Such media may include, but is not limited to, vegetable oils, fish oils, animal fats, hydrogenated vegetable oils, partially hydrogenated vegetable oils, synthetic triglycerides, modified triglycerides, fractionated triglycerides, and mixtures thereof. Triglycerides used in these pharmaceutical compositions may include those selected from the group consisting of almond oil; babassu oil; borage oil; blackcurrant seed oil; black seed oil; canola oil; castor oil; coconut oil; com oil; cottonseed oil; evening primrose oil; grapeseed oil; groundnut oil; mustard seed oil; olive oil; palm oil; palm kernel oil; peanut oil; rapeseed oil; safflower oil; sesame oil; shark liver oil; soybean oil; sunflower oil; hydrogenated castor oil; hydrogenated coconut oil; hydrogenated palm oil; hydrogenated soybean oil; hydrogenated vegetable oil; hydrogenated cottonseed and castor oil; partially hydrogenated soybean oil; soy oil; glyceryl tricaproate; glyceryl tricaprylate; glyceryl tricaprate; glyceryl triundecanoate; glyceryl trilaurate; glyceryl trioleate; glyceryl trilinoleate; glyceryl trilinolenate; glyceryl tricaprylate / caprate; glyceryl tricaprylate / caprate / laurate; glyceryl tricaprylate / caprate / linoleate; glyceryl tricaprylate / caprate / stearate; saturated polyglycolized glycerides; linoleic glycerides; caprylic / capric glycerides; modified triglycerides; fractionated triglycerides; and mixtures thereof.

[0129] Various fatty acids may be utilized in the pharmaceutical compositions disclosed herein. These include, without limitation, both long and short chain fatty acids. Examples of such fatty acids include, but are not limited to, docosahexaenoic acid, caprylic acid, capric acid, lauric acid, butyric acid, and pharmaceutically acceptable salts thereof. Generally, the peptoid compounds described herein are administered in a therapeutically effective amount. “Therapeutically effective amount” means the amount of a compound that, when administered to a subject for treating or preventing an infection, is sufficient to effect such treatment or prevention of the infection. The therapeutically effective amount of the peptoid compound may be determined by a physician, in the light of the relevant circumstances, including the condition to be treated, the chosen route of administration, the peptoid compound administered, the age, weight, and response of the individual subject, the severity of the subject’s symptoms, and the like.

[0130] In some embodiments, the effective amount for intranasal administration may be from 0.1 - 100 mg / Kg / day, 0.5 - 80 mg / Kg / day, 1 - 50 mg / Kg / day, or 2 - 30 mg / Kg / day. In some embodiments, the effective amount for parenteral administration may be from 0.01 - 50 mg / Kg / day, 0.1 - 40 mg / Kg / day, 1 - 30 mg / Kg / day, or 2 - 20 mg / Kg / day. In some embodiments, the effective amount for topical administration may be from 0.1 - 100 mg / Kg / day, 0.5 - 80 mg / Kg / day, 1 - 50 mg / Kg / day, or 2 - 30 mg / Kg / day. In some embodiments, the effective amount for oral administration may be from 0.1 - 60 mg / Kg / day, 0.5 - 50 mg / Kg / day, 1 - 40 mg / Kg / day, or 2 - 25 mg / Kg / day.

[0131] Moreover, these compositions may be administered in a single dose, multi-dose or controlled release fashion.

[0132] The term “administering”, “administered” and grammatical variants refers to the physical introduction of an agent to a subject, using any of the various methods and delivery systems known to those skilled in the art. Exemplary routes of administration include intranasal, intravenous, intramuscular, subcutaneous, intraperitoneal, spinal, intrathecal or other parenteral routes of administration, for example by injection or infusion. The phrase “parenteral administration” means modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intramuscular, intraarterial, intrathecal, intralymphatic, intralesional, intracapsular, intraorbital, intraocular, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal, epidural and intrastemal injection and infusion, as well as in vivo electroporation. Non-parenteral routes include oral, topical, epidermal or mucosal route of administration, for example, intranasally, vaginally, rectally, sublingually or topically. Administering can also be performed, for example, once, a plurality of times, and / or over one or more extended periods.

[0133] In some embodiments, the administration may be one, two, three, or four times per day, once per week, once every two weeks, once per month, or any combinations thereof. Formulation for topical administration may include, for example, dry powder formulation with a polymer to potentially extend residence time and drug release rate, spray on foam, topical gel, and an aqueous solution. These formulations can be dressed with a bandage or hemostatic gauze to maintain the formulation in place on the skin and to provide a protective barrier for skin healing. A powder formulation containing drug and polymer may be provided in a capsule, sachet, stick pack or other single- and / or multi-unit dose packaging, where it could be administered directly or suspended in an aqueous solution for irrigation and administration. A simple powder formulation may be dissolved in an aqueous solution for irrigation and administration. A spray on foam formulation or a gel formulation may be administered via a small aerosol container.

[0134] The pharmaceutical compositions disclosed herein may be manufactured as tablets, liquids, gels, foams, ointments or powders. In some embodiments, these compositions may be applied as microparticles or nanoparticles.

[0135] Packaging for such peptoid formulations can include for example, but not limited to soft gel capsules, hard gelatin capsules, tubes, tubs, sticks, aerosol or manual (pump) sprays, etc.

[0136] In some embodiments, the formulations described herein may include one or more chelation agents. In some embodiments, the chelation agent may be an efficacious anticalculus agent including, but not limited to, one or more of zinc, hexametaphosphates, and diphosphonates. In some embodiments, the formulations described herein may include one or more chelation agents selected from aminopolycarboxylic acids, citric acid, edetate disodium anhydrous, edetate calcium disodium anhydrous citrate salts, sodium gluconate, transferrins, polymers, and any combinations thereof. In some embodiments, the aminopolycarboxylic acids may be selected from the group consisting of tetraxetan (DOTA), nitrilotriacetic acid (NTA), Ethylenediaminetetraacetic acid (EDTA or EDTA acid), ethylene glycol-bis(P-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA or egtazic acid), l,2-bis(o-aminophenoxy)ethane- N,N,N',N'-tetraacetic acid (BAPTA), pentetic acid, diethylenetriaminepentaacetic acid (DTP A) nicotianamine, ethylenediamine-N,N'-bis(2 hydroxyphenylacetic acid) (EDDHA), Ethylenediamine-N,N' -disuccinic acid (EDDS), and any combinations thereof.

[0137] Non-limiting formulation examples illustrating representative pharmaceutical compositions that may be prepared in accordance with the present disclosure are described in Example 3.

[0138] The one or more peptoids may be included in the formulation over a range of 0.005% - 5%. Example buffer agents include, without limitation, histidine buffer for pH control in the physiological range, and may be utilized over a molarity range of lOmM - 100 mM. Example viscosity increasing agents include, but are not limited to, carbomers, polyvinylpyrrolidone (PVP), hydroxyethylcellulose (HEC), and poloxamers, and may be present in a range of 2- 10%. Osmolality increasing agents can also include, but are not limited to, sorbitol, sodium citrate, or dextrose, and may be included at 1-5%. Preservatives may be included in the range of 0.05% - 2%, and can also include, but are not limited to, benzalkonium chloride and sodium benzoate.

[0139] In some embodiments, the compositions described herein may be formulated as mixtures of one or more peptoids. For example, these mixtures may comprise peptoids in various molar ratios, such as 0.01 :0.99 to 0.99:0.01, or any ratio in between. In some embodiments, the effective amount for systemic administration may be from 0.01 - 50 mg / Kg / day, 0.1 - 40 mg / Kg / day, 1 - 30 mg / Kg / day, or 2 - 20 mg / Kg / day. In some embodiments, the effective amount for topical administration may be from 0.1 - 100 mg / Kg / day, 0.5 - 80 mg / Kg / day, 1 - 50 mg / Kg / day, or 2 - 30 mg / Kg / day. In some embodiments, the effective amount for oral administration may be from 0.1 - 60 mg / Kg / day, 0.5 - 50 mg / Kg / day, 1 - 40 mg / Kg / day, or 2 - 25 mg / Kg / day.

[0140] In some embodiments, a composition may comprise the one or more peptoid compounds described herein in mixtures or combinations with other agents, such as known antibiotic, antifungal, or antiviral compounds. In some embodiments, the peptoid compounds of the present disclosure may act synergistically with the known antibiotic, antifungal, or antiviral compounds, so that the resulting composition demonstrates improved effectiveness.

[0141] In some embodiments, the present disclosure relates to a method of preventing or treating an infection of the nasal passages, sinuses, or both of a subject. The method comprises administering a composition described herein, in an amount effective to prevent or treat the infection of the nasal passages, sinuses, or both.

[0142] In some embodiments, the subject may be a vertebrate animal. In some embodiments, the subject may be a mammal. In some embodiments, the subject may be a primate. In some embodiments, the subject may be a human. In some embodiments, the methods disclosed herein have veterinary applications and can be used to treat non-human animals, such as wild, domestic, working, and farm animals, including, but not limited to, camels, horses, llamas, alpacas, donkeys, oxen, cattle, sheep, goats, pigs, dogs, cats, rabbits, bees and poultry.

[0143] “Treating” or “treatment” of an infection, e.g., of the nasal passages, sinuses, or both, refers, in some embodiments, to aiding in healing of the nasal passages, sinuses, or both, ameliorating various damage (e.g., arresting or reducing worsening damage or at least one of the symptoms related to the damage). In some embodiments “treating” or “treatment” refers to ameliorating at least one physical parameter, which may not be discernible by the subject. In some embodiments, “treating” or “treatment” refers to inhibiting an infection of the nasal passages, sinuses, or both, and improving the condition of the subject’s nasal passages, sinuses, or both, either physically, (e.g., stabilization of a discernible symptom), physiologically, (e.g., stabilization of a physical parameter), or both.

[0144] “Preventing” or “prevention” as used herein refers to a reduction in risk of acquiring an infection of the nasal passages, sinuses, or both (e.g.., causing at least one of the clinical symptoms of the infection not to develop in a subject not yet exposed to or predisposed or susceptible to the infection, and not yet experiencing or displaying symptoms of the disease).

[0145] In some embodiments, the term “treating” or “treatment” of a subject’s nasal passages, sinuses, or both, encompasses preventing or inhibiting an infection in the subject’s nasal passages, sinuses, or both. In some embodiments, an infection may be a viral infection, a bacterial infection, a fungal infection, or any combination thereof.

[0146] In some embodiments, the present disclosure relates to a composition comprising one or more peptoid compounds and one or more pharmaceutically acceptable excipients.

[0147] The term “pharmaceutically acceptable” generally means acceptable for administration to a subject, for pharmaceutical purposes, as would be understood by persons of ordinary skill in the art. In some instances, the term “pharmaceutically acceptable” means approved by a regulatory agency of the federal or a state government or listed in the U.S. Pharmacopoeia or other generally recognized pharmacopoeia for use in animals, and more particularly in humans.

[0148] In some embodiments, a topical formulation of the present disclosure may be, or may comprise, a cream, an ointment, a lotion, a gel, a paste, a liniment, a spray, a foam, a serum, a powder, a mousse, a balm, liposomes, a hydrogel, a microemulsion, a nanoemulsion, a salve, a salve stick, or any combinations thereof.

[0149] The peptoid compounds described herein can also be administered in sustained release forms or from sustained release drug delivery systems.

[0150] The components described herein for a formulation of the present disclosure are merely representative. Other materials as well as processing techniques and the like are known in the art, for example as described in Remington’s Pharmaceutical Sciences, 17th edition, 1985, Mack Publishing Company, Easton, Pa.; Remington: The Science and Practice of Pharmacy (22nd ed.)., Troy, D. B., & Beringer, P. (Eds.) (2012), Lippincott Williams & Wilkins; Pharmaceutical Dosage Forms and Drug Delivery Systems (11th ed.)., Ansel, H. C., Allen, L. V. Jr., & Popovich, N. G. (Eds.) (2016), Lippincott Williams & Wilkins; Dermatological and Transdermal Formulations, Walters, K. A., & Hadgraft, J. (Eds.) (2002), CRC Press; Topical Drug Delivery Formulations, Osborne, D. W., & Amann, A. H. (Eds.) (2002), Marcel Dekker; and Cosmetic Dermatology: Principles and Practice (2nd ed.)., Baumann, L. (Ed.) (2009) McGraw-Hill Education, all of which are incorporated herein by reference.

[0151] Excipients and additives of the present disclosure may include, without limitation, various carriers, emulsifiers, chelation agents, stabilizers, enhancers, preservatives, pH adjusters, texture and sensory modifiers, fragrances, antioxidants, anticoagulants, and botanical extracts, among others.

[0152] In some embodiments, the compositions described herein may include one or more excipients in an amount by weight (w / w) of, or in an amount by weight (w / w) of about, 0.01% to 50%, 0.1% to 40%, 1% to 30%, or 2% to 20%, 5% to 25%, or 10% to 20%.

[0153] In some embodiments, the compositions a described herein may include one or more excipients in an amount by weight (w / w) of, or in an amount by weight (w / w) of about, up to 0.5%, up to 1%, up to 2%, up to 4%, up to 6%, up to 8%, up to 10%, up to 15%, up to 20%, up to 30%, up to 40%, or up to 50%.

[0154] In some embodiments, the administration may be one, two, three, four, five, or six times per day. In some embodiments, the administration may be constant or substantially constant, for a period of time. In some embodiments, the period of time may be up to 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, 24 hours, or up to 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, or up to 2 weeks, 3 weeks, 4 weeks, or up to 2 months, 3 months, 4 months, 5 months, 6 months, or up to a year or more.

[0155] In some embodiments, the compositions and methods described herein may be combined with other compositions and methods, including known active ingredients, compositions and methods, either in the same composition, or administered separately. In some embodiments, the compositions and methods of the present disclosure may act synergistically with the other active ingredients, compositions and methods, so that the resulting compositions and / or methods demonstrate improved effectiveness. In some embodiments, the compositions and methods described herein may be useful for applications as consumer products, such as over-the counter products, or products prescribed by a healthcare professional.

[0156] In some embodiments, the compositions described herein are non-toxic, show improved tolerability, improved stability, improved efficacy, or any combinations thereof, compared to previously existing compositions and products.

[0157] EXAMPLES

[0158] The present examples are provided for illustrative purposes only. They are not intended to and should not be interpreted to encompass the full breadth of the invention.

[0159] Example 1. Preparation of peptoid compounds

[0160] The peptoid compounds listed in Table 1 were prepared using a sub-monomer protocol, on Rink Amide MB HA Resin. Example sub-monomer protocols are described in Zuckermann, R. N., Kerr, J. M., Kent, S. B. H, & Moos, W. H. (1992) J. Am. Chem. Soc., 114, 10646-10647 and in U.S. Pat. No. 8,445,632 and U.S. Pat. No. 6,887,845, the entireties of which are incorporated herein by reference. The starting reagents are bromoacetic acid and a small set of primary amines that are readily available commercially. The crude peptoid products were then cleaved from the resin and sidechain protective groups were removed in one step by acidolysis. The resulting residue was then resolubilized and lyophilized twice to produce peptoids as a dry powder. The peptoid products were then purified by HPLC to produce peptoids in powder form, with hydrochloride as the counter ion. Peptoid compounds were stored as dry powder at -20°C and protected from light prior to preparation of stock solutions.

[0161] Table 1. Peptoid compounds tested against various pathogens

[0162] Chemical structures of the peptoid compounds listed in Table 1 are shown in FIG. 1 - FIG. 6. An initial stock concentration of each peptoid compound was prepared in tubes at 2 mg / ml in phosphate-buffered saline (PBS) pH 7.4 (Gibco; cat no. 10010023). Initial dissolution of lyophilized peptoid compound powders to create a stock solution was performed by gentle mixing by inverting the stock solution tube several times), followed by checking for turbidity, precipitation, or aggregate before proceeding to the next steps. If gentle inversion was insufficient to achieve a solution, the stock solution tube was briefly vortexed. The stock solution was then checked for any undissolved particulate, aggregates, or precipitation before proceeding to the next step. If gentle inversion and vortexing was insufficient to achieve a solution, the stock solution tube was briefly sonicated for 15-60 seconds. The stock solution was then checked again for any undissolved particulate, aggregates, or precipitation before proceeding to the next step. If turbidity, precipitation, or aggregate was observed at the initial stock concentration, the initial stock concentration was solubilized by diluting further in PBS to 1 mg / ml. Aliquots of the stock solutions were dispensed in polypropylene vials, protected from light, and stored at -20°C or -80°C prior to use.

[0163] Before testing, the aliquots were carefully observed for any signs of turbidity, precipitation or aggregate during sample preparation and were mixed, vortexed, or sonicated as needed.

[0164] Example 2. Example formulations of peptoid compounds

[0165] Topical Formulation Approaches

[0166] Topical formulation approaches include powder, solution, suspension, semisolids, or infused into a bandage or other dressing material. Powder formulations include, but are not limited to, powder, granulation, pellets, or mini tablets. These powder dosage forms may be packaged or contained in a simple stick pack, sachet, vial, spray, shaker bottle, or multi-use bottle. The solution formulations may be provided as a solution, granules or powder for reconstitution, disintegrating tablet for dissolution and reconstitution, or incorporated into a spray bottle, with or without materials to provide a scaffold or topical bandage to protect the skin. The suspension formulations include, but are not limited to, aqueous suspension, suspension in another solvent, granules or powder for suspension, or disintegrating tablet for resuspension. These suspension dosage forms may be packaged or contained in a simple stick pack, sachet, vial, shaker bottle, or multi-use bottle. Semisolid formulation approaches include, but are not limited to, creme, gel, ointment, lotion, paste, balm, salve, emulsion, suppository (e.g. embedded in wax or polymer that liquifies at body temperature), spray, including spray on bandages, foam, including spray on foams, or film. Peptoids can also be infused into dressings including gauze, and bandages, among others. Peptoids may be applied using a disintegrating tablet, drug eluting tablet or tablets, drug eluting beads or granules, or dissolvable sheet, wafer, block or embedded in wax or polymer that liquifies at body temperature), or thin wafer applied for drug elution.

[0167] Other delivery methods In addition to topical formulation approaches, other administration approaches of the peptoids may be employed, including transdermal patch or other transdermal approach, to provide one or more peptoid compounds described herein.

[0168] Example formulation:

[0169] Stearyl alcohol (250 g) and a white petrolatum (250 g) may be melted at about 75° C. and then a mixture of a peptoid compound described herein (1 - 100 g g) methylparaben (0.25 g), propylparaben (0.15 g), sodium lauryl sulfate (10 g), and propylene glycol (120 g) dissolved in water (about 370 g) may be added and the resulting mixture is stirred until it congeals. One or more peptoid compounds described herein may be admixed.

[0170] Example Liquid formulation:

[0171] A peptoid compound described herein may be admixed with sucrose (1.75 g) and xanthan gum (4 mg) and the resultant mixture may be blended, passed through a No. 10 mesh U.S. sieve, and then mixed in water. Sodium benzoate (10 mg), flavor, and color are diluted with water and added with stirring. Sufficient water may then be added to produce a total volume of 5 mL.

[0172] Example Powder formulation:

[0173] The peptoids (also referred to herein as “drug substance”) may be administered as a simple powder as a standalone drug or with additional excipients to improve flowability or other processing requirements. This powder may be filled into a hard gelatin capsule and subsequently filled into bottles, or packaged in a sachet, stick pack, vial, or other container to aid in portability and ease of administration. This powder formulation may be applied directly, or dissolved in an aqueous vehicle for topical administration. A powder for topical administration may be prepared using the following formula:

[0174] • Drug Substance- 600 g (active ingredient)

[0175] • Microcrystalline cellulose- 100 g (processing aid- flowability)

[0176] • Lactose- 300 g (processing aid- flowability)

[0177] Step 1- blend the microcrystalline cellulose and lactose in a suitable blender and blend for 10 minutes Step 2- add the drug substance and blend for an additional 10 minutes, or until the drug is uniformly distributed throughout the blender.

[0178] Step 3- discharge the powder blend from the blender into a suitable bin or container to store until the filling operation.

[0179] Step 4- fill the appropriate amount of blend into each package for storage, transfer, and administration.

[0180] Formulation Example - Granulation

[0181] The drug substance powder can also be incorporated into a granulation that can produce a particle with improved flowability and density relative to the powder described above. This granulation can be prepared either dry, or in the presence of water or other solvent. The binder may be added either wet (in the granulation solution) or dry with the rest of the materials. If water or other solvent is used, the blend is dried in a suitable pharmaceutical drier, such as a vacuum oven, forced air oven, or fluid bed drier. This granulation may be filled into a hard gelatin capsule and subsequently filled into bottles, or packaged in a sachet, stick pack, vial, or other container to aid in portability and ease of administration. This granulation formulation may be applied directly, or dissolved in an aqueous vehicle for topical administration. A granule formulation that may be used for topical application or dissolution into a topical solution may be prepared using the following formula:

[0182] Formulation example:

[0183] • Drug substance- 700 g (active ingredient)

[0184] • Microcrystalline cellulose- 200 g (diluent and processing aid)

[0185] • Povidone- 100 g (binder)

[0186] • Water (processing aid; removed during processing)

[0187] Step 1- add the active and excipients to a suitable pharmaceutical mixer or granulator such as a planetary mixer, high-shear granulator, fluid bed granulator, or extruder.

[0188] Step 2- slowly add the water while the mixer is operating until all the water has been added.

[0189] Step 3- continue the granulation step until the granulation endpoint is achieved.

[0190] Step 4- discharge the wet mass into a container suitable to hold the material until drying. Step 5- charge the wet mass into a suitable drier and dry until the endpoint of less than 2% water is reached.

[0191] Step 6- discharge the dried granulation into a suitable bin or container to store until the filling operation.

[0192] Step 7- fill the appropriate amount of granulation into each package for storage, transfer, and administration.

[0193] Additional formulation examples are shown below, and follow a similar procedure for preparation.

[0194] Formulation example:

[0195] • Drug substance- 700 g (active ingredient)

[0196] • Microcrystalline cellulose- 275 g (diluent and processing aid)

[0197] • Povidone- 75 g (binder)

[0198] • Croscarmellose sodium- 50 g (disintegrant)

[0199] • Water (processing aid; removed during processing)

[0200] Formulation example:

[0201] • Drug substance- 600 g (active ingredient)

[0202] • Microcrystalline cellulose- 300 g (diluent and processing aid)

[0203] • Hydroxypropyl cellulose- 100 g (binder)

[0204] • Water (processing aid; removed during processing)

[0205] Formulation example:

[0206] • Drug substance- 800 g (active ingredient)

[0207] • Microcrystalline cellulose- 125 g (diluent and processing aid)

[0208] • Hydroxypropyl cellulose- 50 g (binder)

[0209] • Croscarmellose sodium- 25 g (disintegrant)

[0210] • Water (processing aid; removed during processing)

[0211] Formulation Example - Pellets

[0212] The drug substance powder can also be incorporated into a pellet that can produce a particle with improved flowability and density relative to the powder described above, and better flowability than the granulations described above. These pellets may be filled into a hard gelatin capsule and subsequently filled into bottles, or packaged in a sachet, stick pack, vial, or other container to aid in portability and ease of administration. Pellet formulations that may be used for topical application or dissolution into a topical solution may be prepared using similar formulations to those described above, with the addition of 2 processing steps. This pellet formulation may be applied directly, or dissolved in an aqueous vehicle for topical administration. Pellet formulation examples are shown here:

[0213] Formulation example:

[0214] • Drug substance- 700 g (active ingredient)

[0215] • Microcrystalline cellulose- 200 g (diluent and processing aid)

[0216] • Povidone- 100 g (binder)

[0217] • Water (processing aid; removed during processing)

[0218] Formulation example:

[0219] • Drug substance- 700 g (active ingredient)

[0220] • Microcrystalline cellulose- 275 g (diluent and processing aid)

[0221] • Povidone- 75 g (binder)

[0222] • Croscarmellose sodium- 50 g (disintegrant)

[0223] • Water (processing aid; removed during processing)

[0224] Formulation example:

[0225] • Drug substance- 600 g (active ingredient)

[0226] • Microcrystalline cellulose- 300 g (diluent and processing aid)

[0227] • Hydroxypropyl cellulose- 100 g (binder)

[0228] • Water (processing aid; removed during processing)

[0229] Formulation example:

[0230] • Drug substance- 800 g (active ingredient)

[0231] • Microcrystalline cellulose- 125 g (diluent and processing aid)

[0232] • Hydroxypropyl cellulose- 50 g (binder)

[0233] • Croscarmellose sodium- 25 g (disintegrant)

[0234] • Water (processing aid; removed during processing)

[0235] Step 1- add the active and excipients to a suitable pharmaceutical mixer or granulator such as a planetary mixer, high-shear granulator, fluid bed granulator, or extruder.

[0236] Step 2- slowly add the water while the mixer is operating until all the water has been added.

[0237] Step 3- continue the granulation step until the granulation endpoint is achieved. Step 4- Load the wet mass into a suitable extruder and extrude using a screen with apertures between 300 m and 800 gm.

[0238] Step 5- extrude the wet mass and introduce the extrudate into the marumerizer for pellet formation and spheronization.

[0239] Step 6- discharge the wet mass of pellets into a container suitable to hold the material until drying.

[0240] Step 7- charge the wet mass into a suitable drier and dry until the endpoint of less than 2% water is reached.

[0241] Step 8- discharge the dried pellets into a suitable bin or container to store until the filling operation.

[0242] Step 9- fill the appropriate amount of pellets into each package for storage, transfer, and administration.

[0243] Formulation Example - Mini Tablets

[0244] The drug substance powder can also be incorporated into minitablets that can produce a particle with similar performance characteristics as a pellet. Minitablets offer another dry formulation approach, where a solvent may not be required. These minitablets typically have a diameter on the order of 500 - 2000 j m may be filled into a hard gelatin capsule and subsequently filled into bottles, or packaged in a sachet, stick pack, vial, or other container to aid in portability and ease of administration. These minitablet formulations may be applied directly, or dissolved in an aqueous vehicle for topical administration. Minitablet formulation examples are shown below:

[0245] Formulation example:

[0246] • Drug substance- 600 g (active ingredient)

[0247] • Microcrystalline cellulose- 300 g (diluent)

[0248] • Lactose- 100 g (diluent)

[0249] • Hypromellose (HPMC)- 50 g (binder)

[0250] • Colloidal silicon dioxide- 50 g (glidant)

[0251] • Magnesium stearate- 5 g (lubricant)

[0252] Formulation example:

[0253] • Drug substance- 600 g (active ingredient)

[0254] • Silicified microcrystalline cellulose- 400 g (diluent) • Hypromellose (HPMC)- 50 g (binder)

[0255] • Colloidal silicon dioxide- 50 g (glidant)

[0256] • Magnesium stearate- 5 g (lubricant)

[0257] Formulation

[0258] • Drug substance- 600 g (active ingredient)

[0259] • Silicified microcrystalline cellulose- 400 g (diluent)

[0260] • Polyvinylpyrrolidone (PVP)- 50 g (binder)

[0261] • Colloidal silicon dioxide- 50 g (glidant)

[0262] • Magnesium stearate- 5 g (lubricant)

[0263] Formulation

[0264] • Drug substance- 700 g (active ingredient)

[0265] • Silicified microcrystalline cellulose- 250 g (diluent)

[0266] • Polyethylene glycol (PEG)- 50 g (binder)

[0267] • Colloidal silicon dioxide- 50 g (glidant)

[0268] • Magnesium stearate- 5 g (lubricant)

[0269] Formulation Example - Cream

[0270] A topical cream formulation may be prepared using the following formula for the preparation of a batch of approximately 1 Kg:

[0271] • Methyl paraben- 0.25 g (preservative)

[0272] • Propyl paraben- 0.15 g (preservative)

[0273] • Polysorbate 60- 10 g (emulsifier)

[0274] • Propylene glycol- 120 g (viscosity modifier)

[0275] • Stearyl alcohol- 200 g (oleaginous phase)

[0276] • White petrolatum- 200 g (oleaginous phase)

[0277] • Purified water- 470 g (aqueous base)

[0278] Step 1- mix the stearyl alcohol and white petrolatum and heat to approximately 75°C to melt the base.

[0279] Step 2- Dissolve the remaining excipients in the purified water by stirring until a solution is obtained.

[0280] Step 3- Add approximately 5 g of drug substance to the purified water solution and mix for 5 additional minutes to dissolve the drug to manufacture a 5% ointment. Step 4- Slowly incorporate the aqueous solution to the oleaginous base and mix until it is well mixed.

[0281] Step 5- Fill the cream into a suitable package such as a tube or pump bottle.

[0282] Formulation Example - Gel

[0283] Topical gels can be used for sustained-release of actives, provide lubrication, and a carrier of pharmaceutical agents. Hydrogels are water-based and are less oily than creams or ointments, as well as exhibit excellent spreading properties, and may exhibit a higher retention time. Hydrogels can be simple formulations and may provide for a higher drug capacity than oil based formulations due to the high aqueous solubility of the drug substance. Gel formulation examples are shown here:

[0284] Formulation example:

[0285] • Drug Substance- 50 g (active)

[0286] • Carbopol- 300 g (polymer / viscosity)

[0287] • Purified Water- 650 g (solvent)

[0288] Formulation example:

[0289] • Drug Substance- 50 g (active)

[0290] • Sodium carboxymethylcellulose- 400 g (polymer / viscosity)

[0291] • Purified Water- 550 g (solvent)

[0292] Formulation example:

[0293] • Drug Substance- 50 g (active)

[0294] • Hypromellose- 200 g (polymer / viscosity)

[0295] • Purified Water- 750 g (solvent)

[0296] Step 1- Slowly add the polymer to the purified water while stirring slowly using a suitable mixer such as a Silverson mixer. Continue to mix until the polymer exhibits a lump- free dispersion.

[0297] Step 2- Slowly add the drug substance to the polymer dispersion and mix until dissolved.

[0298] Step 3- Fill the gel into a suitable package such as a tube or pump bottle. Formulation Example - Ointment

[0299] Hydrophilic ointment may be prepared using the following formula for the preparation of about 1 Kg of base:

[0300] Formulation example:

[0301] • Methyl paraben- 0.25 g (preservative)

[0302] • Propyl paraben- 0.15 g (preservative)

[0303] • Sodium lauryl sulfate- 10 g (emulsifier)

[0304] • Propylene glycol- 120 g (viscosity modifier)

[0305] • Stearyl alcohol- 250 g (oleaginous phase)

[0306] • White petrolatum- 250 g (oleaginous phase)

[0307] • Purified water- 370 g (aqueous base)

[0308] Step 1- mix the stearyl alcohol and white petrolatum and heat to approximately 75°C to melt the base.

[0309] Step 2- Dissolve the remaining excipients in the purified water by stirring until a solution is obtained.

[0310] Step 3- Add approximately 1 g of drug substance to the purified water solution and mix for 5 additional minutes to dissolve the drug to manufacture a 1% ointment.

[0311] Step 4- Slowly incorporate the aqueous solution to the oleaginous base and mix until it congeals.

[0312] Step 5- Fill the ointment into a suitable package.

[0313] Example 3. Nonhuman primate nasal infection model study

[0314] This example describes a study of peptoid MXB-22,510 activity against MRS A in a model of chronic rhinosinusitis (CRS) that is comparable to human clinical cases. CRS is polymicrobial (bacterial and fungal - multiple kingdoms of pathogens) and is a common drugresistant infection, making it chronic and serious. Non-Human Primates (NHP), including Rhesus macaques, are considered the most relevant non-human species for the intranasal evaluation of antimicrobial agents since their nasal anatomical structures allow for optimal extrapolation to the human condition. The study was conducted in a total of 24 Rhesus macaque monkeys for the evaluation of MXB-22,510 against nasally inoculated MRSA (Study 1 - Study G-003 / 2024) and C. albicans (Study 2 - Study G-002 / 2024), when administered twice daily intranasally under mild sedation, two puffs per nostril, in a volume of 100 uL / puff and a concentration of 100 ug / ml. Twelve Rhesus macaques were assigned to each of Study 1 and Study 2, randomized in each to a ratio of 10 treated to 2 placebo controls.

[0315] In study 1 (MRSA), the treatment group (n=10) was initially treated with MXB-22,510 for a fixed period of 3 days prior to inoculation with the human strain of MRS A, in order to provide preliminary information on the safety of MXB-22,510 as well as the efficacy of MXB-22,510 on the nasal commensal microbial community. Thereafter, partial immunosuppression, induced by oral administration of dexamethasone in drinking water at a concentration of 4mg / L for 5 days prior to inoculation, along with 2% mupirocin administered intranasally BD, was used to induce successful nasal inoculation with MRSA BAA-1717, with the intent of preserving normal physiological anti-infective processes (local barrier mechanisms, innate and adaptive immune responses) reflective of the expected clinical use of MXB-22,510. Nasal swabs were used to confirm colonization of the nasal cavity, after which treatment was administered intranasally with MXB-22,510 for 11 days. During this second treatment period, nasal swab samples of both the left and right middle meatus and nasopharynx was performed for evaluation of effect of MXB-22,510 on inoculated MRSA as measured by culture and CFU counts, nasal brushings for cytological evaluation, and Shotgun Metagenomics for evaluation of changes in the commensal microbiota. Follow-up examination of the animals was conducted 14 days after the final administration of MXB-22,510. Blood samples for evaluation of the pharmacokinetics of MXB-22,510 was collected on Day 1, Day 4, and Day 11, and samples for hematology, clinical chemistry, and coagulation were collected at baseline prior to the first dosing period, after the first dosing period of 3 days, prior to the first dose of the second dosing period, immediately after completion of the second dosing period, and at the last follow-up visit.

[0316] In study 2 (C. albicans'), partial immunosuppression was also induced by oral administration of dexamethasone in drinking water at a concentration of 4mg / L for 5 days prior to inoculation, and continued for the duration of the treatment period of 9 days in order to better differentiate between treatment effect and physiological eradication of the C. albicans. Confirmation of colonization, treatment with MXB-22,510, nasal swabs for monitoring of efficacy, laboratory safety samples, cytology, Shotgun Metagenomics, and follow-up were performed in the same manner as for study 1. Pharmacokinetics was not performed in study 2. Prior to conducting study 1 and study 2, the microbial susceptibility as measured by the minimum inhibitory concentrations (MIC) of the MRSA ATCC BAA-1717 to MXB-22,510 and commonly used comparators vancomycin and chloramphenicol were determined. Table 2 summarizes the results below. Table 2: Microbial Susceptibility Testing Results

[0317] * Strains used in the study; MIC- Minimum Inhibitory Concentration

[0318] Mean Recovery from Intranasal Infection of MRSA

[0319] FIG. 8 is a graph reporting example results of treating MRSA infection in nonhuman primate nasal cavity using peptoid MXB-22,510 and control. The counts were normalized to 100% for comparative purposes. MRSA CFU counts averaged 176% after 3 days in untreated control primates, while the MRSA CFU counts reduced to 2% of baseline after 3 days of treatment with MXB-22,510 . MXB-22,510 effectively eradicated MRSA after 3 days. Mean Recovery from Intranasal Infection of Candida albicans

[0320] FIG. 9 is a graph reporting example results of treating Candida albicans infection in nonhuman primate nasal cavity using peptoid MXB-22,510 and control. The counts were normalized to 100% for comparative purposes. C albicans CFU counts averaged 25.07% after 3 days in untreated control primates, while the C. albicans CFU counts decreased to 2.35% of baseline after 3 days of treatment with MXB-22,510. MXB-22,510 effectively eradicated Candida albicans after 3 days.

[0321] MXB-22,510 effectively eradicated both kingdoms of pathogens after only 3 days.

[0322] Safety

[0323] MXB-22,510 was well-tolerated and safety was established. No Adverse Events or side effects were observed during the study.

[0324] There was no significant effect on nasal microbiome. MXB-22,510 does not adversely affect the commensal microbiome population in the nasal cavity, as reflected by an increase in both the alpha diversity and beta diversity of the nasal microbiome as observed and as calculated using the Chaol and Shannon Indices (FIG 10A-D). In in vitro assays, the Minimum Inhibitory Concentration (MIC) for commensal Staphylococcus aureus was 3.125 pg / mL while that for pathogenic MRSA ATCC BAA-1717 was 0.39 pg / mL.

[0325] FIG. 10 A, FIG. 10B and FIG. 10C are graphs reporting example results of increase in alpha diversity of nasal microbiome in nonhuman primate nasal cavity using peptoid MXB- 22,510 and control.

[0326] FIG. 10D is a graph reporting example results of increase in beta diversity of nasal microbiome in nonhuman primate nasal cavity using peptoid MXB-22,510 and control.

[0327] ***

[0328] The above disclosure contains various examples of peptoid compound compositions and methods of use thereof. Aspects of these various examples may all be combined with one another, even if not expressly combined in the present disclosure, unless they are clearly mutually exclusive.

[0329] In addition, various example materials are discussed herein and are identified as examples, as suitable materials, and as materials included within a more generally described type of material, for example by use of the term “including” or “such-as.” All such terms are used without limitation, such that other materials falling within the same general type exemplified but not expressly identified may be used in the present disclosure as well.

[0330] Furthermore, unless it is otherwise clear that a single entity is intended, terms such as “a,” “an,” and “the” are not intended to refer to only a singular entity and include the general class of which a specific example is described for illustration. In addition, unless it is clear that a precise value is intended, numbers recited herein should be interpreted to include variations above and below that number that may achieve substantially the same results as that number, or variations that are “about” the same number. Finally, a derivative as disclosed herein may include a chemically modified molecule that has an addition, removal, or substitution of a chemical moiety of the parent molecule.

[0331] It is understood the use of the alternative (e.g., “or”) herein is taken to mean either one or both or any combination thereof of the alternatives. The term “and / or” used herein is to be taken mean specific disclosure of each of the specified features or components with or without the other. For example, the term “and / or” as used in a phrase such as “A and / or B” herein is intended to include “A and B,” “A or B,” “A” (alone), and “B” (alone). Likewise, the term “and / or” as used in a phrase such as “A, B, and / or C” is intended to encompass each of the following aspects: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone).

[0332] As used herein, terms “comprising”, “including”, “having” and “containing”, and their grammatical variants, as used herein are intended to be non-limiting so that one item or multiple items in a list do not exclude other items that can be substituted or added to the listed items. It is understood that wherever aspects are described herein with the language “comprising,” otherwise analogous aspects described in terms of “consisting of’ and / or “consisting essentially of’ are also provided.

[0333] Various compositions may be identified by trade name in this application. All such trade names refer to the relevant composition or instrument as it existed as of the earliest filing date of this application, or the last date a product was sold commercially under such trade name, whichever is later. One of ordinary skill in the art will appreciate that variant compositions and instruments sold under the trade name at different times will typically also be suitable for the same uses.

[0334] The above disclosed subject matter is to be considered illustrative, and not restrictive, and the appended claims are intended to cover all such modifications, enhancements, and other implementations which fall within the true spirit and scope of the present disclosure. Thus, to the maximum extent allowed by law, the scope of the present disclosure is to be determined by the broadest permissible interpretation of the following claims and their equivalents and shall not be restricted or limited by the foregoing detailed description.

Claims

CLAIMS1. A composition for use in preventing or treating an infection of the nasal passages, sinuses, or both of a subject, the composition comprising one or more peptoid compounds in an amount effective to prevent or treat the infection of the nasal passages, sinuses, or both.

2. The composition for use according to claim 1, wherein the one or more peptoids are selected from: a peptoid compound H-Ntridec-NLys-Nspe-Nspe-NLys- NH2; a peptoid compound H-Ntetradec-NLys-Nspe-Nspe-NLys-NLL; a peptoid compound H-Ndec-Nlys-Nspe-Nspe(p-Br)-Nlys-Npse-Nspe(p-Br)-NH2; and any combination thereof wherein each peptoid is in an amount effective to prevent or treat the infection of the nasal passages, sinuses, or both.

3. The composition of claim 1, wherein the infection is a pathogenic bacteria infection, a pathogenic fungus infection, a pathogenic virus infection, or a combination thereof, wherein the infection is associated with a pathogenic disease or a pathogenic condition.

4. The composition of claim 3, wherein the pathogenic bacteria are selected from the group consisting of Acinetobacter spp., Bacteroides spp., Citrobacter spp., Cory neb acterium spp., Enterobacter spp., Enterococcus spp., Escherichia coli, Fusobacterium spp., Haemophilus influenzae, Klebsiella spp., Moraxella catarrhalis, Mycobacterium spp., Peptostreptococcus spp., Porphyromonas spp.,Prevotella spp., Cutibacterium acnes. Proteus spp., Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus spp., Streptococcus spp. and any combinations thereof.

5. The composition of claim 1, wherein the pathogenic fungus is selected from the group consisting of Alternaria spp., Apiospermum spp., Aspergillus spp., Bipolaris spp., Blastomyces dermatitidis, Candida spp., Chrysosporium spp., Cladosporium spp., Coccidioides spp., Cryptococcus neoformans, Curvularia spp., Drechslera spp., Emericella nidulans, Exserohilum spp., Histoplasma spp., Mucor spp., Myriodontium keratinophilum, Paecilomyces spp., Paracoccidioides spp., Penicillium melinii,Pseudallescheria boydii, Rhizopus spp., Scedosporium spp., Schizophyllum commune, Sporothrix schenckii., and any combinations thereof.

6. The composition of claim 1, wherein the pathogenic virus is selected from the group consisting of Adenovirus, Coronavirus, Cytomegalovirus (CMV) (in immunocompromised), Echovirus, Human metapneumovirus (HMPV), Influenza virus, Parainfluenza virus, Rhinovirus, and any combinations thereof.

7. The composition of claim 1, wherein the effective amount of the composition does not inhibit growth of a commensal bacteria species, a commensal fungal species, a commensal virus species, or any combination thereof.

8. The composition of claim 1, wherein the effective amount of the composition inhibits growth of a commensal bacteria species, a commensal fungal species, a commensal virus species, or any combination thereof by no more than 99%, 90%, 75%, 66%, 50%, 40%, 30%, 20%, 10%, 5%, 2%, or 1%, or wherein the effective amount of the composition inhibits growth of a commensal bacteria species, a commensal fungal species, a commensal virus species, or any combination thereof by no more than a 2 log reduction.

9. The composition of claim 7, wherein the commensal bacteria species is selected from the group consisting of Acinetobacter spp. (e.g., A. junii, A. indicus), Acidocella spp., Aeromonas spp., Aggregatibacter spp., Alicy cliphilus spp., Asticcacaulis spp., Bradyrhizobium spp., Chryseobacterium spp., Citrobacter spp., Cloacibacterium spp., Clostridium spp., Coprobacillus spp. Cory neb acterium spp. (e.g., C. accolens, C. amycolatum, C. aurimucosum, C. propinquum, C. pseudodiphtheriticum, C. segmentosum, C. striatum, C. tuberculostearicum), Cutibacterium spp. (e.g., C. acnes), Diaphorobacter spp., Dolosigranulum spp. (e.g., D. pigrum),Elizabethkingia spp. (e.g., E. anopheles), Enterobacter spp., Escherichia spp., Exiguobacterium spp., Flavobacterium spp., Fusobacterium spp.,Haemophilus spp. (e.g., H. influenzae), Helicobacter spp., Hyphomicrobiaceae (family), Klebsiella spp., Lactobacillus spp. (e.g., L. sakei), Lawsonella spp., Leptotrichia spp., Micrococcus spp. (e.g., M. luteus), Moraxella spp. (e.g., M. catarrhalis), Neisseria spp. (e.g., N subflava, N. flavescens), Paenibacillus spp., Pedobacter spp., Peptoniphilus spp., Prevotella spp. (e g-, P- melaninogenica),Propionib acterium spp. (e.g., P. acnes, P. avidum, P. granulosum),Pseudoalteromonas spp., Pseudomonas spp. (e.g., P. aeruginosa, P. oleovorans), Ralstonia spp. (e.g., R. pickettii), Rheinheimera spp., Shewanella spp., Sphingobacterium spp., Staphylococcus spp. (e.g., S. aureus, S. capitis, S. epidermidis, S. hominis, S. lugdunensis), Stenotrophomonas spp. (e.g., S. maltophilia'), Streptococcus spp. (e.g., S. mitis, S. parasanguinis, S. pneumoniae, S. pyogenes, S. saUvarius), Streptomyces spp., Veillonella spp. (e.g., V. atypica, V. dispar, V. parvula). Vibrio spp, and any combinations thereof.

10. The composition of claim 7, wherein the commensal fungal species is selected from the group consisting of Alternaria spp. (e.g., A. alternata, A. breviramosa), Aspergillus spp. (e.g., A. fumigatus, A. peniciHioides), Aureobasidium spp. (e.g., A. pullulans), Bipolaris spp. (e.g., B. papendorfii), Cladosporium spp. (e.g., C. cladosporioides, C. delicatulum), Coniochaeta spp. (e.g., C. fasciculala). Cryptococcus spp. (e.g., C. neoformans), Fusarium spp., Malassezia spp. (e.g., M. globosa, M. reslricla , Penicillium spp.chrysogenum), Pleosporales (order), Rhodosporidium spp. (e.g., R. diabovatum), Saccharomyces spp., Scutellospora spp., Trichosporon spp, and any combinations thereof.

11. The composition of claim 7, wherein the commensal virus is selected from the group consisting of Adenoviridae (family), Alphacoronavirus (genus), Anellovirus (genus), Betacoronavirus (genus), Cystovirus (genus) Enterovirus (genus), Herpesviridae (family), Klebsiella phages (various strains), Lambda-like viruses (genus), Myovirus (genus), N4- like viruses (genus), Papillomaviridae (family), Pseudomonas virus phi 12 (species), Rhinovirus (genus), Siphovirus (genus), Tl-like viruses (genus), and any combinations thereof.

12. The composition of claim 1, formulated for intranasal administration.

13. The composition of claim 12, wherein the effective amount for intranasal administration is from 0.1 - 100 mg / Kg / day, 0.5 - 80 mg / Kg / day, 1 - 50 mg / Kg / day, or 2 - 30 mg / Kg / day.

14. The composition of claim 1, formulated for administration one, two, three, or four times per day, once per week, once every two weeks, or once per month, or any combinations thereof.

15. A method of preventing or treating an infection of the nasal passages, sinuses, or both, of a subject, the method comprising: administering a composition of any of claims 1-14, in an amount effective to prevent or treat the infection of the nasal passages, sinuses, or both.

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