36 results about "Viral protease" patented technology

The invention relates to the technical field of anti-enterovirus medicines, in particular to application of Enractevir in preparation of an anti-enterovirus medicine. According to the invention, efficient screening of candidate drugs is realized through a multi-channel virus reporting system based on a TAT trans-activation effect, and a small molecule compound drug Enractevir with a specific antiviral effect on enterovirus group A 71 and enterovirus group D 68 is obtained. Enractevir improves the interferon secretion level of host cells by inhibiting the activity of enterovirus 2A / 3C protease, thereby inhibiting virus replication and proliferation. Enractevir plays a role through double-target 2A / 3C protease, and the risk of virus drug resistance can be reduced. According to the technical scheme, the technical problem that in the prior art, specific drugs for the two kinds of enteroviruses are lacked can be solved, a standardized treatment scheme is provided for prevention and control of enterovirus related diseases in the global range, and the medicine has remarkable public health significance and wide application and popularization value.

The invention relates to a related substance of a coronavirus 3CLpro protease inhibitor compound as shown in a formula (IV), a preparation method of the related substance and application of the related substance as an impurity reference substance in detection of the related substance of the compound as shown in the formula (IV), and the scientificity and accuracy of impurity detection of the compound as shown in the formula (IV) can be effectively improved by taking the related substance as the reference substance. The impurity content of the compound of the formula (IV) and the preparation thereof can be effectively and conveniently monitored, and the quality of the compound of the formula (IV) and the preparation thereof is favorably controlled, so that the safety and effectiveness of the compound and the preparation thereof are ensured.

Vaccine compositions for protecting a subject against diseases caused by viral pathogens of the Picornaviridae family are disclosed. These vaccines comprise nucleic acids encoding the capsid polyprotein (P1 polyprotein) mixed with the viral 3C protease that processes the P1 polyprotein, and encapsulated within nanoparticle carriers. Methods of preventing, reducing, inhibiting, or delaying the symptoms of an infection caused by a viral pathogen, or of inducing an immune response against a viral pathogen in a subject are provided. Methods of making the vaccines are also described.

The present application discloses an antiviral fusion protein. Specifically, the present application provides an antiviral fusion protein, which comprises a cell death inducing domain (lethal domain), a domain inhibiting the activity of the lethal domain (inhibitory domain) and a protease recognition sequence capable of removing or destroying the function of the inhibitory domain; the fusion protein has the activity of inducing cell death after being cut by a specific viral protease, thereby killing the cells infected by the virus in a targeted manner. The present application also discloses a programmable method for inducing the death of virus-infected cells, which comprises transferring the above-mentioned fusion protein or nucleic acid into cells so that the cells die before replication and assembly after being infected by the virus, thereby achieving timely and effective elimination of the virus.

The invention relates to process development of a preparation prescription of a coronavirus 3CL protease inhibitor compound Iscartrevir and a preparation method of the coronavirus 3CL protease inhibitor compound Iscartrevir. By strictly screening and optimizing the formula, the preparation with a specific prescription ratio is obtained. According to the preparation, the medicine stability is improved, through the overall synergistic effect of the dry granulation step, in the preparation process of the medicine components, the flowing property of totally mixed materials is good, and the sticking problem is further solved. Meanwhile, the preparation is simple in production process, short in production period, energy-saving, efficient, low in cost and suitable for industrial mass production.

The present invention provides the use of 4,3',5'-trihydroxy resveratrol compounds in the preparation of coronavirus 3CL protease inhibitors. The present invention discovers that 4,3',5'-trihydroxy resveratrol and its analogs have the activity of inhibiting coronavirus 3CL protease, and can play an anti-coronavirus role by inhibiting the activity of coronavirus 3CL protease. Among them, piceatannol, oxyresveratrol, physcion, 2,6,3',5'-tetrahydroxy stilbene, cis-tartriloside, 4-hydroxy resveratrol, and 4,3',5'-trihydroxy resveratrol have a half-maximal inhibitory concentration (IC50) against SARS-CoV and SARS-CoV-2 3CL proteases lower than 10 μM, showing good anti-coronavirus 3CL protease effect, effectively inhibiting the activity of coronaviruses, and can potentially be used for the prevention and / or treatment of coronavirus infections, and further for the preparation of drugs for the prevention and / or treatment of coronavirus infections.

Proteases of Group IV (+)ssRNA viruses were found to act on a human sequences in addition to the viral sequences. The identity of the cleavable human sequences is disclosed. Detection of these sequences can act as a diagnostic of infection. It is contemplated that these findings could be employed to facilitate post-translational silencing at the level of protein (e.g., removal of existing proteins), thus serving as a protein analog to CRISPR / Cas9 and RNAi / RISC, and further to enable sequence-specific silencing of host functions without the modification of the host genome.

The invention relates to a crystal and application of a virus protease inhibitor, in particular to a crystal form of a compound 1 or pharmaceutically acceptable salt thereof and application thereof. The invention also relates to a preparation method of the crystal form, a composition containing the crystal and a pharmaceutical composition. The crystal form is stable, high in yield, mild in crystallization condition, suitable for industrial production and capable of well meeting the requirements of the pharmaceutical industry.

The invention discloses a salt form of a coronavirus 3CL protease inhibitor PLC-01 as well as a preparation method and application of the salt form, and belongs to the technical field of medicinal chemistry. Salt types of PLC-01 comprise inorganic acid salt, organic acid salt, sodium salt and a free state. According to the present invention, various organic acids, inorganic acids and solvents are mainly screened so as to obtain the PLC-01 hydrochloride Pattern A, the PLC-01 mesylate Pattern A, the PLC-01 sodium salt Pattern C and the PLC-01 free state Pattern A, wherein the PLC-01 hydrochloride Pattern A, the PLC-01 mesylate Pattern A, the PLC-01 sodium salt Pattern C and the PLC-01 free state Pattern A have characteristics of high purity and good stability; the invention also discloses a pharmaceutical composition of the salt form of the compound shown in the formula I. All salt forms of PLC-01 in the invention have strong inhibition efficacy on 3CL protease, and are expected to become novel active pharmaceutical ingredients for preventing or treating novel coronavirus infection.

The application belongs to the field of pharmaceutical chemical industry and relates to a cyclic peptide compound shown as formula M or a stereoisomer, a tautomer or a mixture thereof of the compound, a pharmaceutically acceptable salt, a polymorph, a co-crystal or a solvate of the compound, or a stable isotope derivative, a metabolite or a prodrug of the compound. The application also relates to a method for synthesizing the cyclic peptide compound and an intermediate. The provided cyclic peptide compound has a strong inhibitory effect on a coronavirus 3CL protease and a small RNA virus (for example, an enterovirus EV71 virus) 3C protease. After cell level activity testing, the provided cyclic peptide compound has an obvious inhibitory effect on EV71 virus and coronavirus and the like, indicating that the cyclic peptide compound shown as formula M can produce a viral inhibitory effect at the cell level by inhibiting viral protease activity, and has a good application prospect as an antiviral drug.

The present invention pertains to compounds that inhibit Flavivirus NS2B-NS3 proteases and are potent and selective inhibitors of the West Nile virus and Zika virus. The compounds of the invention can be used alone or in combination with other agents to treat infections caused by these viruses. Additionally, the invention relates to pharmaceutical compositions containing these compounds.

Crystallization and Use of Viral Protease Inhibitors. Specifically, this invention relates to the crystalline form of Compound 1 or a pharmaceutically acceptable salt thereof and its use. The invention also relates to methods for preparing the crystalline form, as well as compositions containing the crystals and pharmaceutical compositions. The crystalline form is stable, has high yield, involves mild crystallization conditions, is suitable for industrial production, and can fully meet the requirements of the pharmaceutical industry.

Provided are uses of a viral 3C protease or a nucleic acid molecule encoding a 3C protease for the prevention and / or treatment of a tumor in a subject (e.g., a human), and for the preparation of a medicament for the prevention and / or treatment of a tumor in a subject (e.g., a human).

Provided is a compound represented by general formula (I), or a tautomer, mesomer, racemate, enantiomer, diastereomer, or pharmaceutically acceptable salt thereof, and use thereof for preparing an antiviral protease inhibitor drug.

The present invention relates to the technical field of medicinal chemistry, and particularly to a method for preparing a 3-tetrazolylmethyl-1,3,5-triazin-2,4-dione compound inhibiting coronavirus 3CL protease activity and use thereof. Specifically, a compound of Formula I, or a pharmaceutically acceptable salt, or an optical isomer, or an isotope-substituted form thereof is provided. The compound effectively inhibits the SARS-CoV-2 3CLpro activity, and is useful in the preparation of a SARS-CoV-2 3CLpro inhibitor to block the replication and transcription of SARS-CoV-2 viruses in patients. The compound prepared in the present invention has high in-vitro safety, and very good prospect of application in the preparation of SARS-CoV-2 3CLpro inhibitors and anti-SARS-CoV-2 drugs.

Provided herein are compositions and methods that allow for controlled interaction between a target protein and a polypeptide to which a binding protein is fused. Compositions and methods utilize a target protein that binds to the hepatitis C virus protease inhibitor glaprevir to form a complex, and a Tn3 binding protein that specifically binds to the complex. The target protein is or is derived from a viral protease, such as an HCV NS3 / 4A protease.

The present document describes compounds that are inhibitors of coronavirus proteases, and more particularly to compounds that are inhibitors of SARS-CoV-2 viral proteases. Also, the present document describes methods and uses of the compounds for the treatment or prevention of viral infection, such as SARS-CoV-2 infections, in a subject in need of treatment.

A kind of compound containing N-(substituted sulfonyl) acetamide structure as shown in formula I, its pharmaceutically acceptable salt, its isomer, its hydrate or its solvate, and its application as viral protease inhibitor in preparation of antiviral drugs.The provided peptide compound has strong inhibitory effect on coronavirus 3CL protease and small RNA virus (such as enterovirus EV71 virus) 3C protease.Through cell level activity test, the N-(substituted sulfonyl) acetamide structure compound has obvious inhibitory effect on small RNA virus (such as enterovirus EV71 virus) virus and coronavirus, etc., as shown in formula I, the compound containing N-(substituted sulfonyl) acetamide structure can produce viral inhibition effect on cell level by inhibiting viral protease activity, and has good antiviral drug application prospect.

The invention discloses a virus protease, EV71 2Apro and SARS-CoV-23CLpro, which can promote the extracellular level of LRPAP1 to be increased, and the LRPAP1 can degrade IFNAR1 (interferon-related protein 1) and inhibit subsequent interferon signal transduction. In addition, the inhibition of LRPAP1 by a composition containing alpha2M, siRNA, or other LRPAP1 inhibitors can improve RNA virus and DNA virus infections. The invention not only expands the relevance between lipoprotein metabolism and host innate immune response, but also lays a foundation for the development of broad-spectrum antiviral drugs.

The invention provides viral protease inhibitors having the general formula (I) wherein the variables are as described herein, compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds.

The present application provides a preparation (pharmaceutical composition) containing an uracil derivative showing coronavirus 3CL protease inhibitory activity, a pharmaceutically acceptable salt thereof, or a solvate thereof as an effective ingredient. In addition, the present application provides a crystal of an uracil derivative showing coronavirus 3CL protease inhibitory activity, a pharmaceutically acceptable salt thereof, or a solvate thereof.

Disclosed herein are methods for preventing or treating a viral infection, e.g., coronavirus, enterovirus, norovirus, picornavirus, rhinovirus, and / or a herpes virus infection. In certain embodiments, this disclosure relates to peptidomimetic heterocyclic compounds and pharmaceutical compositions comprising the same for uses in methods disclosed herein.

The present invention provides: a viral protease inhibitor having the general formula (I), wherein the variables are as described herein; comprising the compound; methods of making the compounds; and methods of using the compounds. # imgabs0 #

Provided herein, inter alia, are compounds, pharmaceutical compositions and methods related to the treatment of viral infections caused by coronavirus or enterovirus. Provided herein are compounds of Formula (I), (II) and (III)and methods of using the compounds for therapy. These compounds are peptidomimetics that inhibit protease 3CL of a coronavirus, and are useful for treating conditions caused by viral infections, including COVID-19.

The present invention relates to a flavivirus NS2B-NS3 protease inhibitor, a compound that inhibits the replication of flaviviruses in cells. The compounds of the present invention are useful alone or in combination with other agents for use in the treatment of infectious diseases caused by flaviviruses, particularly dengue virus, West Nile virus, chikungunya virus, Japanese encephalitis virus.

The present invention provides compositions comprising extracts from specific plant genera or alternatives thereof, including Lithospermum and Oryza or alternatives thereof, along with optional extracts from Scutellaria and Boswellia. The compositions thus include shikonin, anthocyanins, and other bioactive compounds such as flavonoids and boswellic acids. Additional ingredients like ivermectin, metformin, and curcumin may be incorporated. The compositions are designed as multi-targeted therapeutic agents, combining viral protease inhibitors, endogenous host protease inhibitors, anti-inflammatory agents, and anti-senescence agents. These compositions are intended for treating various medical conditions, including respiratory diseases, viral infections, inflammatory conditions, immune-related disorders, liver conditions, and neurological conditions. The invention describes methods of treatment and use in manufacturing medicaments for these conditions.

The application discloses a compound with a structural formula I, wherein the compound has good 3CL protease inhibitory activity, has significant proliferation inhibitory activity on virus-infected cells, and has potential application value in treating diseases related to virus infection. The compound has good solubility and permeability, good in-vivo metabolic stability, high in-vivo exposure, and high bioavailability, and is a potential drug compound.

The present disclosure relates to a method of reducing or arresting viral load in a subject infected with a coronavirus, the method comprising the step of administering to the subject a therapeutically effective amount of a viral protease inhibitor. In some embodiments, the subject is a human. In one embodiment, the coronavirus is SARS-CoV-19 and the viral protease inhibitor is frovatriptan (6R)-6-(methylamino)-6,7,8,9-tetrahydro-5H-carbazole-3-carboxamide.

This invention is in the field of medicinal pharmacology. In particular, the present invention relates to pharmaceutical agents which function as inhibitors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral replication and / or SARS-CoV-2 related viral 3CL protease (Mpro) activity. The invention further relates to methods of treating and / or ameliorating symptoms related to conditions caused by the SARS-CoV-2 virus (e.g., COVID-19), comprising administering to a subject (e.g., a human patient) a composition comprising one or more pharmaceutical agents which function as inhibitors of SARS-CoV-2 viral replication and / or inhibitors of SARS-CoV-2 related Mpro activity.