Casiopeinas® as SARS-CoV-2 main protease (M^pro) inhibitors: a combined DFT, molecular docking and ONIOM approach

Abstract

Casiopeinas® are well-known planar copper compounds with potent anticancer activity; their general formulae are [Cu(N-N)(L-L)]n+ (n= 1,2), where N-N= 4,7-dimethyl-1,10-phenanthroline or 4,4’-dimethyl-2,2’-bipyridine and L-L= different bidentate chelates. The CasIII-ia: [Cu(4,7-dimethyl-1,10-phenanthroline)(acacetylacetonate)]NO3...

Interaction of copper potential metallodrugs with TMPRSS2: A comparative study of docking tools and its implications on COVID-19

“…Among them, the square planar complex [Cu(L) 2 ], where L = 2-(4-morpholinobenzylideneamino)phenol ( Sakthikumar et al, 2022 ), shows binding energy of −7.8 kcal mol −1 against M pro with Autodock Vina (interactions are not specified), higher than the results of the copper complexes with Arg, Orn, and Lys, here studied. In addition, fifty Casiopeinas ® and related Cu(II) compounds were also investigated as M pro inhibitors with AutoDock ( Reina et al, 2022 ). Some Casiopeinas ® , such as CasII-5Clsa, CasII-ambz, or CasII-tyr, show promising results with binding energies between −8.58 and −9.25 and kcal·mol −1 , lower than the references boceprevir and N3 peptide, and they interact with His41, Asn142, Cys145, Glu166, and Gln189, which are part of the catalytic site cavity of M pro ( Kneller et al, 2020 ).…”

“…Even though these compounds are important because they fight cancer, parasites, and bacteria, new research has been done to explore their inhibitory effect against the main protease, M pro , which is responsible for the replication and primary transcription of the SARS-CoV-2 virus’s genetic material. It was concluded that most studied Casiopeinas ® could inhibit M pro more efficiently than free monochelates, bioactive ligands, and boceprevir (a recognized inhibitor) ( Reina et al, 2022 ).…”

Therapeutic potential of Cordyceps militaris mushroom against SARS-CoV-2 : Virtual screening against Mpro and in vitro validation

“…Cordycepin was found to be making Pi-Alkyl interaction with H61 of this catalytic dyad. M49, a member of the substrate union triad [33][34] was also found to make a hydrogen bond with cordycepin. Along with these interactions, several other residues contribute to accommodating the molecules by making hydrophobic or pi-cation interactions (Fig.…”

Casiopeinas® third generation, with indomethacin: synthesis, characterization, DFT studies, antiproliferative activity, and nanoencapsulation

“…37–39 In addition, in silico studies suggest that all the three Casiopeinas® generations can act as antiviral agents by the inhibition of the main protease of SARS-CoV-2. 40…”

“…[37][38][39] In addition, in silico studies suggest that all the three Casiopeinas® generations can act as antiviral agents by the inhibition of the main protease of SARS-CoV-2. 40 Indomethacin is a nonsteroidal anti-inammatory drug (NSAID) that inhibits cyclooxygenases (COX). 41 In cancer disease, COX-2, an isoform of COX enzymes, is expressed in numerous solid tumors and their neovasculature.…”