Bacillus species; a potential source of anti-SARS-CoV-2 main protease inhibitors

Abstract

The COVID-19 being a preconized global pandemic by the World Health Organization needs persuasive immediate research for possible medications. The present study was carried out with a specific aim to computationally evaluate and identify compounds derived from Bacillus species as the plausible inhibitors against 3-chymotrypsin-like main protease (3CLpro) or main protease (M^Pro), which is a key enzyme in the life-cycle of coronavirus. The compounds were isolated from the crude extracts of Bacillus species. Among the isolated compounds, novel inhibitory leads were identified using in silico techniques. Molecular docking revealed that stigmasterol (-8.3 kcal/mol), chondrillasterol (-7.9 kcal/mol) and hexadecnoic acid (-6.9 kcal/mol)) among others bind in the substrate-binding pocket and also interacted with the catalytic dyad of the 3-CLpro. Further evaluation using 50 ns molecular dynamic simulation and MMPB-GBSA indicated that among the top three docking hits, hexadecanoic acid was found to be the most promising anti-COVID-19 lead against the main protease. Hexadecanoic acid might serve as a potent anti-SARS-CoV-2 compound to combat COVID-19, however, in vitro and in vivo validation and optimization is needed.

Communicated by Ramaswamy H. Sarma

Keywords:

• Bacillus subtilis
• COVID-19
• 3-chymotrypsin-like main protease
• anti-SARS-CoV-2
• molecular docking
• molecular dynamic simulation
• binding free energy

Acknowledgments

The authors are highly grateful to the Higher Education Commission (HEC) Pakistan for financial assistance. We acknowledge the National University of Medical Sciences and The University of Haripur, Haripur, KPK for providing laboratory facilities. All authors would like to acknowledge the participants who contributed to this research and the university staff and administration for their cooperation. The authors would also like to acknowledge unwavering moral and emotional support from family and friends.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by Higher Education Commission of Pakistan.