Deciphering the Potential of Pre and Pro-Vitamin D of Mushrooms against Mpro and PLpro Proteases of COVID-19: An In Silico Approach
Abhay Tiwari,
Garima Singh,
Gourav Choudhir,
Mohit Motiwale,
Nidhi Joshi,
Vasudha Sharma,
Rupesh K. Srivastava,
Satyawati Sharma,
Marco Tutone,
Pradeep Kumar Singour
Affiliations
Abhay Tiwari
Centre for Rural Development & Technology, Indian Institute of Technology (IIT), New Delhi 110016, India
Garima Singh
Centre for Rural Development & Technology, Indian Institute of Technology (IIT), New Delhi 110016, India
Gourav Choudhir
Centre for Rural Development & Technology, Indian Institute of Technology (IIT), New Delhi 110016, India
Mohit Motiwale
Computational and Synthetic Chemistry Lab., Department of Pharmaceutical Chemistry, Faculty of Pharmacy, VNS Group of Institutions, Bhopal 462044, India
Nidhi Joshi
Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA
Vasudha Sharma
Department of Food Technology, Jamia Hamdard, New Delhi 110062, India
Rupesh K. Srivastava
Department of Biotechnology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India
Satyawati Sharma
Centre for Rural Development & Technology, Indian Institute of Technology (IIT), New Delhi 110016, India
Marco Tutone
Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, Università degli Studi di Palermo, 90123 Palermo, Italy
Pradeep Kumar Singour
Computational and Synthetic Chemistry Lab., Department of Pharmaceutical Chemistry, Faculty of Pharmacy, VNS Group of Institutions, Bhopal 462044, India
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.
