<strong>Computational Screening for Potential Drug Candidates Against SARS-CoV-2 Main Protease</strong>

Abstract

Background: SARS-CoV-2 that are the causal agent of a current pandemic are enveloped, positive-sense, single-stranded RNA viruses of the Coronaviridae family. Proteases of SARS-CoV-2 are necessary for viral replication, structural assembly and pathogenicity. The ~33.8KDa Mpro protease of SARS-CoV-2 is a non-human homologue and highly conserved among several coronaviruses indicating Mpro could be a potential drug target for Coronaviruses.Methods: Here we performed computational ligand screening of four pharmacophores (OEW, Remdesivir, Hydroxycholoquine and N3) that are presumed to have positive effects against SARS-CoV-2 Mpro protease (6LU7) and also screened 50,000 molecules from the ZINC Database dataset against this protease target.Results: We found 40 pharmacophore-like structures of natural compounds from diverse chemical classes that exhibited better affinity of docking as compared to the known ligands. The 10 best selected ligands namely, ZINC1845382, ZINC1875405, ZINC2092396, ZINC2104424, ZINC44018332, ZINC2101723, ZINC2094526, ZINC2094304, ZINC2104482, ZINC3984030, and ZINC1531664, are mainly classified as &amp;beta;-carboline, Alkaloids and Polyflavonoids, and all of them displayed interactions with dyad CYS145 and HIS41 from the protease pocket in a similar way as with other known ligands.Conclusion: Our results suggest that these 10 molecules could be effective against SARS-CoV-2 protease and may be tested in vitro and in vivo to develop novel drugs against this virus.

Consensus virtual screening of dark chemical matter and food chemicals uncover potential inhibitors of SARS-CoV-2 main protease

“…[9][10][11][12][13] Moreover, the search for novel compounds commercially available or with the possibility of being synthesized has had a vital rebound (e.g., screening part or the entire ZINC database). 9, [14][15][16] Table 1 summarizes representative examples of virtual screening (VS) studies directed to different molecular targets, including SARS-CoV-2 M pro . Most of these efforts relied on structure-based drug design (SBDD).…”

Consensus Virtual Screening of Dark Chemical Matter and Food Chemicals Uncover Potential Inhibitors of SARS-CoV-2 Main Protease

“…On the other hand, the search for novel compounds with the possibility of being synthesized or acquired commercially has had an important rebound (e.g. screening part or the entire ZINC database) [9,[14][15][16]. Table 1 summarizes representative examples of virtual screening (VS) studies directed to different molecular targets, including SARS-COV-2 M pro .…”