FDA-approved drugs as potential covalent inhibitors of key SARS-CoV-2 proteins: an in silico approach.

Bremelanotide and other FDA-approved drugs may have potential as inhibitors of SARS-CoV-2 proteins, but experimental validation is necessary before considering clinical application.

Summary and findings

This study aimed to identify potential inhibitors of key SARS-CoV-2 proteins using FDA-approved drugs. The compounds bremelanotide, lanreotide, histrelin, and leuprolide were highlighted as potential RdRp inhibitors. Further validation is needed to establish their efficacy and safety.

Abstract

<h4>Background/aim</h4>The COVID-19 pandemic caused by SARS-CoV-2 necessitated rapid development of effective therapeutics, prompting this study to identify potential inhibitors targeting key viral and host proteins: RNA-dependent RNA polymerase (RdRp), main protease (Mpro), transmembrane serine protease 2 (TMPRSS2), and angiotensin-converting enzyme 2 (ACE2).<h4>Methods</h4>We used covalent docking and molecular dynamics (MD) simulations to screen FDA-approved compounds against these targets using diverse covalent reaction mechanisms. Top-ranking compounds underwent further evaluation through MD simulations to assess binding stability and conformational dynamics.<h4>Results</h4>Several promising drug repurposing candidates were identified: bremelanotide, lanreotide, histrelin, and leuprolide as potential RdRp inhibitors; azlocillin, cefiderocol, and sultamicillin for Mpro inhibition; tenapanor, isavuconazonium, and ivosidenib targeting TMPRSS2; and cefiderocol, cefoperazone, and ceftolozane as potential ACE2 inhibitors.<h4>Conclusion</h4>This study provides valuable insights into repurposing existing drugs as potential COVID-19 therapeutics by targeting crucial viral proteins. However, further experimental validation and preclinical studies are necessary to confirm the efficacy and safety of these compounds before consideration for clinical application.

Key findings

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Limitations

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Elsewhere in the PT-141 (Bremelanotide) corpus