A Study of Drug Repurposing to Identify SARS-CoV-2 Main Protease (3CLpro) Inhibitors. 2022

Seri Jo, and Luca Signorile, and Suwon Kim, and Mi-Sun Kim, and Oscar Huertas, and Raúl Insa, and Núria Reig, and Dong Hae Shin
College of Pharmacy and Graduates School of Pharmaceutical Sciences, Ewha W. University, Seoul 03760, Korea.

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wreaked havoc all over the world. Although vaccines for the disease have recently become available and started to be administered to the population in various countries, there is still a strong and urgent need for treatments to cure COVID-19. One of the safest and fastest strategies is represented by drug repurposing (DRPx). In this study, thirty compounds with known safety profiles were identified from a chemical library of Phase II-and-up compounds through a combination of SOM Biotech's Artificial Intelligence (AI) technology, SOMAIPRO, and in silico docking calculations with third-party software. The selected compounds were then tested in vitro for inhibitory activity against SARS-CoV-2 main protease (3CLpro or Mpro). Of the thirty compounds, three (cynarine, eravacycline, and prexasertib) displayed strong inhibitory activity against SARS-CoV-2 3CLpro. VeroE6 cells infected with SARS-CoV-2 were used to find the cell protection capability of each candidate. Among the three compounds, only eravacycline showed potential antiviral activities with no significant cytotoxicity. A further study is planned for pre-clinical trials.

UI MeSH Term Description Entries
D011480 Protease Inhibitors Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES). Antiprotease,Endopeptidase Inhibitor,Endopeptidase Inhibitors,Peptidase Inhibitor,Peptidase Inhibitors,Peptide Hydrolase Inhibitor,Peptide Hydrolase Inhibitors,Peptide Peptidohydrolase Inhibitor,Peptide Peptidohydrolase Inhibitors,Protease Antagonist,Protease Antagonists,Antiproteases,Protease Inhibitor,Antagonist, Protease,Antagonists, Protease,Hydrolase Inhibitor, Peptide,Hydrolase Inhibitors, Peptide,Inhibitor, Endopeptidase,Inhibitor, Peptidase,Inhibitor, Peptide Hydrolase,Inhibitor, Peptide Peptidohydrolase,Inhibitor, Protease,Inhibitors, Endopeptidase,Inhibitors, Peptidase,Inhibitors, Peptide Hydrolase,Inhibitors, Peptide Peptidohydrolase,Inhibitors, Protease,Peptidohydrolase Inhibitor, Peptide,Peptidohydrolase Inhibitors, Peptide
D003546 Cysteine Endopeptidases ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000086402 SARS-CoV-2 A species of BETACORONAVIRUS causing atypical respiratory disease (COVID-19) in humans. The organism was first identified in 2019 in Wuhan, China. The natural host is the Chinese intermediate horseshoe bat, RHINOLOPHUS affinis. 2019 Novel Coronavirus,COVID-19 Virus,COVID19 Virus,Coronavirus Disease 2019 Virus,SARS Coronavirus 2,SARS-CoV-2 Virus,Severe Acute Respiratory Syndrome Coronavirus 2,Wuhan Coronavirus,Wuhan Seafood Market Pneumonia Virus,2019-nCoV,2019 Novel Coronaviruses,COVID 19 Virus,COVID-19 Viruses,COVID19 Viruses,Coronavirus 2, SARS,Coronavirus, 2019 Novel,Coronavirus, Wuhan,Novel Coronavirus, 2019,SARS CoV 2 Virus,SARS-CoV-2 Viruses,Virus, COVID-19,Virus, COVID19,Virus, SARS-CoV-2,Viruses, COVID19
D000086782 Coronavirus 3C Proteases 3C proteases that occur in species of CORONAVIRIDAE. 3C Proteases, Coronavirus,3C-Like Proteinase, Coronavirus,Chymotrypsin-Like Main Protease, Coronavirus,Coronavirus 3C Proteinases,Coronavirus 3CLpro Proteases,Coronavirus 3CLpro Proteinase,M(pro) Protein, Coronavirus,Main Proteinase, Coronavirus,Mpro Protein, Coronavirus,3C Like Proteinase, Coronavirus,3C Proteinases, Coronavirus,3CLpro Proteases, Coronavirus,3CLpro Proteinase, Coronavirus,Chymotrypsin Like Main Protease, Coronavirus,Coronavirus 3C-Like Proteinase,Coronavirus Main Proteinase,Coronavirus Mpro Protein,Proteinase, Coronavirus 3CLpro,Proteinases, Coronavirus 3C
D000093485 COVID-19 Drug Treatment The use of DRUGS to treat COVID19 or its symptoms. COVID-19 Drug Therapy,COVID19 Drug Therapy,COVID19 Drug Treatment,Coronavirus Disease 2019 Drug Treatment,Coronavirus Disease-19 Drug Treatment,COVID 19 Drug Therapy,COVID 19 Drug Treatment,COVID-19 Drug Therapies,COVID19 Drug Therapies,COVID19 Drug Treatments,Coronavirus Disease 19 Drug Treatment,Drug Therapy, COVID-19,Drug Therapy, COVID19,Therapy, COVID-19 Drug,Therapy, COVID19 Drug,Treatment, COVID-19 Drug
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D001185 Artificial Intelligence Theory and development of COMPUTER SYSTEMS which perform tasks that normally require human intelligence. Such tasks may include speech recognition, LEARNING; VISUAL PERCEPTION; MATHEMATICAL COMPUTING; reasoning, PROBLEM SOLVING, DECISION-MAKING, and translation of language. AI (Artificial Intelligence),Computer Reasoning,Computer Vision Systems,Knowledge Acquisition (Computer),Knowledge Representation (Computer),Machine Intelligence,Computational Intelligence,Acquisition, Knowledge (Computer),Computer Vision System,Intelligence, Artificial,Intelligence, Computational,Intelligence, Machine,Knowledge Representations (Computer),Reasoning, Computer,Representation, Knowledge (Computer),System, Computer Vision,Systems, Computer Vision,Vision System, Computer,Vision Systems, Computer
D017361 Viral Nonstructural Proteins Proteins encoded by a VIRAL GENOME that are not structural components of VIRUS PARTICLES. Some of these proteins may play roles within the infected cell during VIRUS REPLICATION or act in regulation of virus replication or VIRUS ASSEMBLY. Nonstructural Proteins, Viral,NS Proteins, Viral,Viral NS Proteins,Viral Non-Structural Proteins,Viral Nonstructural Protein,Viral Nonstructural Proteins NS1,Viral Nonstructural Proteins NS2,Nonstructural Protein, Viral,Viral Non Structural Proteins
D058492 Drug Repositioning The deliberate and methodical practice of finding new applications for existing drugs. Drug Repurposing,Drug Rescue,Repositioning, Drug,Repurposing, Drug,Rescue, Drug

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