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

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 i...

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Published inInternational journal of molecular sciences Vol. 23; no. 12; p. 6468
Main Authors Jo, Seri, Signorile, Luca, Kim, Suwon, Kim, Mi-Sun, Huertas, Oscar, Insa, Raúl, Reig, Núria, Shin, Dong Hae
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 09.06.2022
MDPI
Subjects
antiviral
Artificial intelligence
Chemical bonds
Clinical trials
Coronaviruses
COVID-19
Cytotoxicity
drug repurposing
Drugs
FDA approval
fret
Infections
inhibitory compounds
Ligands
Middle East respiratory syndrome
Protease
Protease inhibitors
Proteinase
Proteinase inhibitors
Respiratory diseases
SARS-CoV-2 3CL protease
Severe acute respiratory syndrome coronavirus 2
Viral diseases
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Summary: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.
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These authors contributed equally to this work.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23126468