Version 1
: Received: 26 April 2024 / Approved: 28 April 2024 / Online: 28 April 2024 (07:07:33 CEST)
How to cite:
de Oliveira Só, Y.A.; Bezerra, K.S.; Gargano, R.; Mendonça, F.L.; de Souto, J.T.; Fulco, U.L.; Pereira Junior, M.L.; Júnior, L.A.R. In Silico Comparative Analysis of Ivermectin and Nirmatrelvir Inhibitors Interacting with the SARS-CoV-2 Main Protease. Preprints2024, 2024041825. https://doi.org/10.20944/preprints202404.1825.v1
de Oliveira Só, Y.A.; Bezerra, K.S.; Gargano, R.; Mendonça, F.L.; de Souto, J.T.; Fulco, U.L.; Pereira Junior, M.L.; Júnior, L.A.R. In Silico Comparative Analysis of Ivermectin and Nirmatrelvir Inhibitors Interacting with the SARS-CoV-2 Main Protease. Preprints 2024, 2024041825. https://doi.org/10.20944/preprints202404.1825.v1
de Oliveira Só, Y.A.; Bezerra, K.S.; Gargano, R.; Mendonça, F.L.; de Souto, J.T.; Fulco, U.L.; Pereira Junior, M.L.; Júnior, L.A.R. In Silico Comparative Analysis of Ivermectin and Nirmatrelvir Inhibitors Interacting with the SARS-CoV-2 Main Protease. Preprints2024, 2024041825. https://doi.org/10.20944/preprints202404.1825.v1
APA Style
de Oliveira Só, Y.A., Bezerra, K.S., Gargano, R., Mendonça, F.L., de Souto, J.T., Fulco, U.L., Pereira Junior, M.L., & Júnior, L.A.R. (2024). In Silico Comparative Analysis of Ivermectin and Nirmatrelvir Inhibitors Interacting with the SARS-CoV-2 Main Protease. Preprints. https://doi.org/10.20944/preprints202404.1825.v1
Chicago/Turabian Style
de Oliveira Só, Y.A., Marcelo Lopes Pereira Junior and Luiz Antônio Ribeiro Júnior. 2024 "In Silico Comparative Analysis of Ivermectin and Nirmatrelvir Inhibitors Interacting with the SARS-CoV-2 Main Protease" Preprints. https://doi.org/10.20944/preprints202404.1825.v1
Abstract
Exploring therapeutic options is crucial in the ongoing COVID-19 pandemic caused by SARS-CoV-2. Nirmatrelvir, a potent inhibitor targeting the SARS-CoV-2 Mpro, shows promise as an antiviral treatment. Additionally, Ivermectin, a broad-spectrum antiparasitic drug, has demonstrated effectiveness against the virus in laboratory settings. However, its clinical implications are still debated. Using computational methods such as molecular docking and 100 ns molecular dynamics simulations, we investigated how Nirmatrelvir and Ivermectin interact with SARS-CoV-2 Mpro(A). Calculations using density functional theory have been instrumental in elucidating the behavior of isolated molecules, primarily by analyzing the frontier molecular orbitals. Our analysis revealed distinct binding patterns: Nirmatrelvir formed strong interactions with amino acids like MET49, MET165, HIS41, HIS163, HIS164, PHE140, CYS145, GLU166, and ASN142, showing stable binding with a root mean square deviation (RMSD) of around 2.0 Å. On the other hand, Ivermectin interacted with THR237, THR239, LEU271, LEU272, and LEU287, displaying an RMSD of 1.87 Å, indicating enduring interactions. Both ligands stabilized Mpro(A), with Ivermectin showing stability and persistent interactions despite forming fewer hydrogen bonds. These findings offer detailed insights into how Nirmatrelvir and Ivermectin bind to the SARS-CoV-2 main protease, providing valuable information for potential therapeutic strategies against COVID-19.
Keywords
main protease (Mpro); ivermectin; nirmatrelvir; SARS-CoV-2; molecular docking; molecular dynamics
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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