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

## TL;DR

This study uses computer modeling to find FDA-approved drugs that could potentially inhibit key SARS-CoV-2 proteins, offering new treatment options for COVID-19.

## Contribution

The novel use of covalent docking and molecular dynamics simulations to repurpose FDA-approved drugs against multiple SARS-CoV-2 targets.

## Key findings

- Bremelanotide, lanreotide, histrelin, and leuprolide show potential as RdRp inhibitors.
- Azlocillin, cefiderocol, and sultamicillin are promising Mpro inhibitors.
- Cefiderocol, cefoperazone, and ceftolozane may inhibit ACE2.

## Abstract

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).

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.

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.

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.