Potential COVID-19 papain-like protease PL pro inhibitors: repurposing FDA-approved drugs

PeerJ

article

Valentina L. Kouznetsova¹  Aidan Zhang²  Mahidhar Tatineni¹  Mark A. Miller¹  Igor F. Tsigelny¹ 

[1] San Diego Supercomputer Center, University of California;REHS Program at San Diego Dupercomputer Center, University of California;Department of Neurosciences, University of California;Science, CureMatch Inc.

关键词: COVID-19;    Papain-like protease;    Computational drug design;    Drugs repurposing;   

DOI  :  10.7717/peerj.9965

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

Using the crystal structure of SARS-CoV-2 papain-like protease (PLpro) as a template, we developed a pharmacophore model of functional centers of the PLpro inhibitor-binding pocket. With this model, we conducted data mining of the conformational database of FDA-approved drugs. This search identified 147 compounds that can be potential inhibitors of SARS-CoV-2 PLpro. The conformations of these compounds underwent 3D fingerprint similarity clusterization, followed by docking of possible conformers to the binding pocket of PLpro. Docking of random compounds to the binding pocket of protease was also done for comparison. Free energies of the docking interaction for the selected compounds were lower than for random compounds. The drug list obtained includes inhibitors of HIV, hepatitis C, and cytomegalovirus (CMV), as well as a set of drugs that have demonstrated some activity in MERS, SARS-CoV, and SARS-CoV-2 therapy. We recommend testing of the selected compounds for treatment of COVID-19.

【 授权许可】

CC BY