In silico evaluation of favipiravir-associated potential new drugs against polymerase enzyme of SARS-CoV-2.

Autor:	Saira; Department of Chemistry, Islamia College Peshawar, Khyber Pakhtunkhwa, 25120, Pakistan., Khan K; Department of Chemistry, Islamia College Peshawar, Khyber Pakhtunkhwa, 25120, Pakistan., Khan A; Department of Chemistry, Islamia College Peshawar, Khyber Pakhtunkhwa, 25120, Pakistan., Khan A; Department of Chemistry, Islamia College Peshawar, Khyber Pakhtunkhwa, 25120, Pakistan., Shah T; Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Khyber Pakhtunkhwa, 25120, Pakistan., Ahmad N; Department of Chemistry, Islamia College Peshawar, Khyber Pakhtunkhwa, 25120, Pakistan., Rashid HU; Center of Chemical, Pharmaceutical and Food Sciences, Federal University of Pelotas, Pelotas, RS, Brazil., Zahoor M; Department of Biochemistry, University of Malakand at Chakdara, Dir Lower, Khyber Pakhtunkhwa, Pakistan., Ullah R; Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia., Bari A; Department of Pharmaceutical Chemistry, College of Pharmacy King Saud University, Riyadh, Saudi Arabia., Umar MN; Department of Chemistry, University of Liverpool, UK.
Jazyk:	angličtina
Zdroj:	Heliyon [Heliyon] 2024 Sep 26; Vol. 10 (19), pp. e38479. Date of Electronic Publication: 2024 Sep 26 (Print Publication: 2024).
DOI:	10.1016/j.heliyon.2024.e38479
Abstrakt:	Millions of lives have been lost to the deadly SARS-CoV-2 virus. Vaccines and antiviral drugs are essential scientific tools in combating viral infections. This in silico study focused on the RdRp inhibitor favipiravir, exploring new analogs by substituting the fluorine atom on the pyrazine ring with both homocyclic and heterocyclic moieties. Initially, ADME and toxicity properties were assessed using SwissADME and ProTox-II online tools. Ligands L6 and L7 exhibited high bioavailability and drug-likeness compared to favipiravir. Subsequently, all new analogs were docked into the RdRp active site using AutoDock Vina, demonstrating high affinity compared to favipiravir. Based on optimal ADMET profiles and docking scores, ligands L4 , L6 , and L7 underwent 200 ns MDS using the CHAARM 36 force field in NAMD software to validate docking results. Various trajectory analyses, including RMSD, RMSF, histograms, total number of contacts, and ligand properties, were conducted to gain insights into the interaction patterns between ligands and RdRp. All protein-ligand complexes exhibited greater stability than favipiravir throughout simulations period. This theoretical study suggests that ligands L6 and L7 could serve as lead candidates for RdRp inhibition. Cell-Based SARS-CoV-2 RdRp Activity Assay is recommended to validate these in silico findings. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2024 The Authors.)
Databáze:	MEDLINE
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