Anti-HIV-drug and phyto-flavonoid combination against SARS-CoV-2: a molecular docking-simulation base assessment

Abstract

At the health emergence, no such potent prophylactic therapy is available to control the deadly emerged Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). However, existing antiviral, anti-inflammatory, antimalarial drugs is the only option against SARS-CoV-2, but it may be harmful to patients without more clinical evidence. As an alternative solution, we proposed a newer hypothesis using the selective 10 potent anti-HIV drugs and flavonoid class of phytochemicals from previous reports to use in combination against SARS-CoV-2. Primarily, 10 anti-HIV protease inhibitor drugs and 10 phyto-flavonoids as ligands in molecular docking study against the putative target, the SARS-CoV-2-main protease (M^pro) ID: 6Y2E), as an essential enzyme in viral genome replication. According to molecular docking and drug-ability scores of each ligand, the anti-HIV drug, the darunavir (with a docking score, −10.25 kcal/mol and drug-likeness rating, 0.60) and the quercetin-3-rhamnoside (with a docking score, −10.90 kcal/mol and drug-likeness rating, 0.82) were selected for further analysis in combined effect. Perceptibly, the combined ‘anti-HIV drug and phyto-flavonoid’ docking complex has actively interacted with eight strong H-bonds with stability, briefly elucidated through RMRD-, RMSF- Rg-plots and MM/PBSA-binding energy calculation during 100 ns than the individual against SARS-CoV-2-M^pro. Thus, the ‘anti-HIV-drug-phyto-flavonoid’ combination therapy could be used against SARS-CoV-2 after some experimental validation.

Communicated by Ramaswamy H. Sarma

Keywords:

• Coronavirus
• severe acute respiratory syndrome
• anti-HIV drugs
• phyto-flavonoid
• molecular docking-simulation

Acknowledgements

This work acknowledges the ‘ICMR-Post Doctoral Fellowship Scheme’ awarded to Dr. Shasank S. Swain (No.3/1/3/PDF(21)/HRD-2019-2) by the Indian Council of Medical Research, Department of Health Research, Govt. of India. Special thanks to the World Health Organization for updated information on COVID-19 in this challenging time. The work is dedicated to our special heroes (Doctors, Nurses, Pharmacists, Associated Healthcare Persons, Police, Leader, Media, etc.) for constant and untiring cooperation in this pandemic situation to save lives from COVID-19.

Authors’ contributions

S.S.S., S.R.S., A.S. conceptualized the research design; S.R.S., A.S, carried out the advanced computation assessments and organized the results according to S.S.S direction; S.S.S. drafted and T.H. edited the MS; S.P. provided overall support.

Disclosure statement

No potential conflict of interest was reported by the authors.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work acknowledges the ‘ICMR-Post Doctoral Fellowship Scheme’ awarded to Dr. Shasank S. Swain (No.3/1/3/PDF(21)/HRD-2019-2) by the Indian Council of Medical Research, Department of Health Research, Govt. of India.