Deciphering the Potential of Pre and Pro-Vitamin D of Mushrooms against Mpro and PLpro Proteases of COVID-19: An In Silico Approach

Abstract

Vitamin D’s role in combating the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the virus causing COVID-19, has been established in unveiling viable inhibitors of COVID-19. The current study investigated the role of pre and pro-vitamin D bioactives from edible mushrooms against Mpro and PLpro proteases of SARS-CoV-2 by computational experiments. The bioactives of mushrooms, specifically ergosterol (provitamin D2), 7-dehydrocholesterol (provitamin-D3), 22,23-dihydroergocalciferol (provitamin-D4), cholecalciferol (vitamin-D3), and ergocalciferol (vitamin D2) were screened against Mpro and PLpro. Molecular docking analyses of the generated bioactive protease complexes unravelled the differential docking energies, which ranged from −7.5 kcal/mol to −4.5 kcal/mol. Ergosterol exhibited the lowest binding energy (−7.5 kcal/mol) against Mpro and PLpro (−5.9 kcal/mol). The Molecular Mechanics Poisson–Boltzmann Surface Area (MMPBSA) and MD simulation analyses indicated that the generated complexes were stable, thus affirming the putative binding of the bioactives to viral proteases. Considering the pivotal role of vitamin D bioactives, their direct interactions against SARS-CoV-2 proteases highlight the promising role of bioactives present in mushrooms as potent nutraceuticals against COVID-19.

The Efficacious Benefit of 25-Hydroxy Vitamin D to Prevent COVID-19: An In-Silico Study Targeting SARS-CoV-2 Spike Protein

“…The findings also point to the potential for expediting the structure-based identification and optimization of a new COVID-19 therapeutic candidate by using simulation-refined models of protein-ligand complexes. Few similar works have been reported so far on 25-hydroxy vitamin D against the main protease (M pro ) and RNA-dependent RNA polymerase (RdRP) [ 81 ], Mpro and PLpro [ 82 , 83 ], endoribonuclease Nsp15 [ 84 ], etc. with impressive docking scores of >−10 Kcal/mol.…”

Sulphotransferase (SOT) genes in wheat providing tolerance against drought and heat

“…The time-dependent uctuation of Rg (radius of gyration) was estimated to establish the in uence of ligand binding on the compactness and structural integrity of ligand-A3P and TaSOT proteins. TaSOT5b-2D shows higher Rg, than other two proteins, that indicates that the higher the Rg higher will be the level of labile nature of the complexes, whereas the lower Rg pro le indicates the contracted nature of the complexes (Tiwari et al 2022).…”

Progress in SARS-CoV-2, diagnostic and clinical treatment of COVID-19

“…For example, many studies have reported that GRL-0617 inhibits viral replication of SARS-CoV-2 because its binding site and mode of inhibition are almost identical to that of SARS-CoV PL pro , and these results further consolidate the position of PLpro as a drug target for antiviral therapy of COVID-19 [ 11 , 12 , [117] , [118] , [119] , [120] ]. Therefore, it is an attractive target for antiviral drug development [ 12 , [121] , [122] , [123] ]. For example, Zhao et al, designed an approach using a SARS-CoV-2 PL pro inhibition activity as the primary screening tool for the discovery of the small molecule inhibitors, with a secondary cell-based assay for evaluation of their antiviral activity.…”