[email protected] Division of Zoology, Faculty of Science, [email protected] Department of Zoology, Faculty of Science, Charles

[email protected] Division of Zoology, Faculty of Science, Charles
[email protected] Department of Zoology, Faculty of Science, Charles University, Vinicna 7, 128 44 Prague, Czech Republic Correspondence: [email protected]: Sur, V.P.; Sen, M.K.; Komrskova, K. In Silico Identification and Validation of Organic Triazole Based Ligands as Prospective Inhibitory Drug β adrenergic receptor Inhibitor Molecular Weight Compounds of SARS-CoV-2 Main Protease. Molecules 2021, 26, 6199. doi/10.3390/ moleculesAbstract: The SARS-CoV-2 virus is very contagious to humans and has brought on a pandemic of global proportions. Despite worldwide study efforts, efficient targeted therapies against the virus are nonetheless lacking. With the ready availability with the macromolecular structures of coronavirus and its known variants, the look for anti-SARS-CoV-2 therapeutics through in silico evaluation has turn out to be a hugely promising field of study. In this study, we investigate the inhibiting potentialities of triazole-based compounds against the SARS-CoV-2 primary protease (Mpro ). The SARS-CoV-2 principal protease (Mpro ) is known to play a prominent function inside the processing of polyproteins that are translated from the viral RNA. Compounds were pre-screened from 171 candidates (collected in the DrugBank database). The outcomes showed that 4 candidates (MEK Inhibitor Source Bemcentinib, Bisoctrizole, PYIITM, and NIPFC) had high binding affinity values and had the possible to interrupt the main protease (Mpro ) activities from the SARS-CoV-2 virus. The pharmacokinetic parameters of those candidates have been assessed and by means of molecular dynamic (MD) simulation their stability, interaction, and conformation were analyzed. In summary, this study identified the most suitable compounds for targeting Mpro, and we recommend using these compounds as prospective drug molecules against SARS-CoV-2 just after follow up studies. Keyword phrases: SARS-CoV-2; most important protease; triazole; docking; MD simulation; drugAcademic Editors: Giovanni N. Roviello and Caterina Vicidomini Received: 10 September 2021 Accepted: 12 October 2021 Published: 14 October1. Introduction Reports suggest that the SARS-CoV-2 virus penetrates target tissues by manipulating two important proteins present around the surface of cells. The two important proteins are transmembrane serine protease two (TMPRSS2) and angiotensin-converting enzyme two (ACE2). The SARS-CoV-2 virus belongs towards the category of human coronaviruses [1], and its genomic organization is similar to that of other coronaviruses [4]. The viral genomic RNA (272 Kb) codes each structural and non-structural proteins. The structural proteins contain membrane (M), envelope (E), nucleocapsid (N), hemagglutinin-esterase (HE), and spike (S) proteins. These proteins are known to facilitate the transmission and replication of viruses in host cells [5]. The replicase gene (ORF1a) and protease gene (ORF1b) encode polyprotein1a (pp1a) and polyprotein1ab (pp1ab). These polyproteins are further processed by Papain-like protease (PLpro) and Chymotrypsin-like protease (3CLpro) to produce nonstructural proteins (nsp) [3,6]. The key protease (Mpro ) is an important enzyme, which plays a very important part within the lifecycle with the virus and may as a result be made use of in study efforts to recognize potential target drugs. Furthermore, because no proteases with Mpro -like cleaving characteristics are found in humans, any possible protease inhibitors are most likely to become nontoxic to humans.Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.Copyright: 2021 by the author.