Turkish Journal of Biology
Abstract
Background/aim: 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). Methods: 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. Results: 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. Conclusion: 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.
Author ORCID Identifier
MURAT SERİLMEZ: 0000-0001-8502-2505
ANWAR ABUELRUB: 0000-0003-0043-5314
İSMAİL EROL: 0000-0001-8256-6283
SERDAR DURDAĞI: 0000-0002-0426-0905
DOI
10.55730/1300-0152.2741
Keywords
COVID-19, covalent docking, molecular dynamics simulation, molecular mechanics-generalized Born surface area
First Page
233
Last Page
246
Publisher
The Scientific and Technological Research Council of Türkiye (TÜBİTAK)
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
SERİLMEZ, M, ABUELRUB, A, EROL, İ, & DURDAĞI, S (2025). FDA-approved drugs as potential covalent inhibitors of key SARS-CoV-2 proteins: an in silico approach. Turkish Journal of Biology 49 (3): 233-246. https://doi.org/10.55730/1300-0152.2741
