A computational study on active constituents of Habb-ul-aas and Tabasheer as inhibitors of SARS-CoV-2 main protease

Abstract

A respiratory pandemic known as coronavirus disease-19 (COVID-19) has created havoc since it emerged from Wuhan, China. COVID-19 is caused by a newly emerged SARS coronavirus (SARS-CoV) with increased pathogenicity named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Due to the lack of understanding of the mechanism of pathogenesis, an effective therapeutic option is unavailable. Epidemics described in Unani ancient literature include nazla-e-wabai and humma-e-wabai, and most of the symptoms of COVID-19 resemble nazla-e-wabai. Hence, in light of Unani literature, the treatment of COVID-19 can be managed with the composites prescribed in Unani medicine for nazla-e-wabai. In this study, a structure-based drug design approach was carried out to check the effectiveness of the pharmacologically active constituents of the Unani composites prescribed to treat nazla-e-wabai against SARS-CoV-2. We performed molecular docking of the active constituents of these composites against the main protease (M^pro), a potential drug target in SARS-CoV-2. Using detailed molecular docking analysis, Habb-ul-aas and Tabasheer were identified as potential inhibitors of SARS-CoV-2 M^pro. The active constituents of both these composites bind to the substrate-binding pocket of SARS-CoV-2 M^pro, forming interactions with key residues of the binding pocket. Molecular dynamics (MD) simulation suggested the binding of active constituents of Habb-ul-aas with SARS-CoV-2 M^pro with a strong affinity as compared to the constituents of Tabasheer. Thus, this study sheds light on the use of these Unani composites in COVID-19 therapeutics.

Communicated by Ramaswamy H. Sarma

Keywords:

• Coronavirus disease 2019
• Unani medicine
• molecular docking
• molecular dynamics simulation
• SARS-CoV-2
• nazla-e-wabai
• main protease

Acknowledgements

SS is highly grateful to the National Institute of Unani Medicine (NIUM), Bengaluru. HA acknowledges NIUM for all the support. M.S.K, F.M.H, and M.T.R. acknowledge the generous support from Scientific Research's Deanship at King Saud University, Riyadh, Kingdom of Saudi Arabia (Grant No. RGP-215). AS thanks to Dr. M. I. Hassan for critical suggestions and editing to this manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.