Comput Biol Chem . Repurposing approved drugs as potential inhibitors of 3CL-protease of SARS-CoV-2: Virtual screening and structure based drug design

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Comput Biol Chem


. 2020 Jul 31;88:107351.
doi: 10.1016/j.compbiolchem.2020.107351. Online ahead of print.
Repurposing approved drugs as potential inhibitors of 3CL-protease of SARS-CoV-2: Virtual screening and structure based drug design


Franz-Josef Meyer-Almes ¹



Affiliations

• PMID: 32769050
• DOI: 10.1016/j.compbiolchem.2020.107351

Abstract

3CL proteases (3CL^pro) are only found in RNA viruses and have a central role in polyprotein processing during replication. Therefore, 3CL^pro has emerged as promising drug target for therapeutic treatment of infections caused by Coronaviruses. In the light of the recent major outbreak of the SARS-CoV-2 virus and the continuously rising numbers of infections and casualties, there is an urgent need for quickly available drugs or vaccines to stop the current COVID-19 pandemic. Repurposing of approved drugs as 3CL^pro inhibitors could dramatically shorten the period up to approval as therapeutic against SARS-CoV-2, since pharmacokinetics and toxicity is already known. Several known drugs, e.g. oxytetracycline, doxorubicin, kanamycin, cefpiramide, teniposide, proanthocyanidin and salvianolic acid B, but also not-approved active compounds from the ZINC15 library were identified as new potential inhibitors of 3CL^pro by using different complementary virtual screening and docking approaches. These compounds have the potential to be further optimized using structure based drug design as demonstrated for oxytetracycline.

Keywords: Antiviral; C30 endopeptidase; COVID-19; Docking; Drug discovery; Pharmacophore; Therapeutic.