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

• Published in: Molecules (Basel, Switzerland) Vol. 27; no. 17; p. 5620
• Main Authors: Tiwari, Abhay, Singh, Garima, Choudhir, Gourav, Motiwale, Mohit, Joshi, Nidhi, Sharma, Vasudha, Srivastava, Rupesh K, Sharma, Satyawati, Tutone, Marco, Singour, Pradeep Kumar
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 31.08.2022; MDPI
• Subjects: Agaricales - metabolism; Alfacalcidol; Biological activity; Calcifediol; Calciferol; Computer applications; Coronaviruses; COVID-19; COVID-19 Drug Treatment; edible mushrooms; Endopeptidases - metabolism; Epidemics; Ergosterol; Force and energy; Functional foods & nutraceuticals; Health aspects; Humans; in-silico studies; Ligands; Medical research; Molecular docking; Molecular Docking Simulation; Molecular Dynamics Simulation; Mushrooms; Pandemics; Peptide Hydrolases - chemistry; pre-vitamin-D; pro-vitamin-D; Protease Inhibitors - chemistry; Proteases; Proteins; Provitamins; SARS-CoV-2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Simulation; Viral diseases; Viral Nonstructural Proteins - metabolism; Viruses; Vitamin D; Vitamin D - pharmacology; Vitamin D2; Vitamin deficiency; India; United States > US; pro-vitamin-D; SARS-CoV-2; edible mushrooms; pre-vitamin-D; in-silico studies
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27175620

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 D ), 7-dehydrocholesterol (provitamin-D ), 22,23-dihydroergocalciferol (provitamin-D ), cholecalciferol (vitamin-D ), and ergocalciferol (vitamin D ) 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.