Abstract
The SARS-CoV-2 virus is highly contagious to humans and has caused a pandemic of global proportions. Despite worldwide research efforts, efficient targeted therapies against the virus are still lacking. With the ready availability of the macromolecular structures of coronavirus and its known variants, the search for anti-SARS-CoV-2 therapeutics through in silico analysis has become a highly promising field of research. In this study, we investigate the inhibiting potentialities of triazole-based compounds against the SARS-CoV-2 main protease (Mpro). The SARS-CoV-2 main protease (Mpro) is known to play a prominent role in the processing of polyproteins that are translated from the viral RNA. Compounds were pre-screened from 171 candidates (collected from the DrugBank database). The results showed that four candidates (Bemcentinib, Bisoctrizole, PYIITM, and NIPFC) had high binding affinity values and had the potential to interrupt the main protease (Mpro) activities of the SARS-CoV-2 virus. The pharmacokinetic parameters of these candidates were assessed and through 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 potential drug molecules against SARS-CoV-2 after follow up studies.
Highlights
Reports suggest that the SARS-CoV-2 virus penetrates target tissues by manipulating two important proteins present on the surface of cells
It can be concluded that Bemcentinib, Bisoctriazole, and PYIITM can be used as potent antiviral drugs against the SARS-CoV-2 virus (Supplementary Table S5), because previous case and clinical studies suggested that some antiviral drugs mostly used for human immunodeficiency virus (HIV) showed effects against SARSCoV-2 virus [31,32]
The present study explored the molecular interactions of ligands, Bemcentinib, Bisoctriazole, PYIITM, and NIPFC
Summary
Reports suggest that the SARS-CoV-2 virus penetrates target tissues by manipulating two important proteins present on the surface of cells. Gaudêncio and Florbela used CADD methodologies to screen natural marine products to identify effective ligands with SARS-CoV-2 main protease (Mpro) with inhibiting potential [13]. (Tianbdleaz1o).l-T3-hyel]ipnhteernayclt}ifounrasntu-2d-ycasrhboowxaemd ifdoeur(NhyIPdFrCog;DenB0b7o0n2d0s).wBiethmcMenprtoinreibsid(DueBs1,2t4h1r1eean wiitnhveHsitsig4a1t,ioannadl odnruegwfoitrhthTehtrr4e5a,tmwehnilteoPf YnoIInT-Msmsahllocweleldluonngecaenleccetrr)o(sFtaigtiucreinSt1eAra,cEt)ioshno(wPied tion, which indicates that all four triazole based ligands have binding affinity with amino acids, which play crucial roles in Mpro inhibition In these terms, it can be concluded that Bemcentinib, Bisoctrizole, PYIITM, and NIPFC can be used as potential Mpro inhibitors. These amino acids are involved in Mpro–Bemcentinib, Mpro–Bisoctrizole, Mpro–PYIITM, and Mpro–NIPFC interaction, which indicates that all four triazole based ligands have binding affinity with amino acids, which play crucial roles in Mpro inhibition ADMET properties of the four selected compounds were analyzed by a free pkCSM (http://biosig. unimelb.edu.au/pkcsm/prediction, accessed on 28 February 2021) web tool
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