Molecular docking-simulation edge assessment of potential and less-toxic ‘anti-HIV-drug and phyto-flavonoid’ combination against SARS-CoV-2

Shasank Swain, Satya Singh, Alaka Sahoo, Tahziba Hussain, Sanghamitra Pati

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Received date: 3rd May 2020

The emergence of the pandemic coronavirus-2019 (COVID-19) disease by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) or 2019-novel coronavirus-2019 (2019-nCoV-2019) has created a disease-ridden environment for the entire human community, globally. However, no potent prophylactic therapy is available to control the deadly emerged viral disease. Repurposing of existing antiviral, antiinflammatory, antimalarial drugs is the only option against SARS-CoV-2. But without any clinical evidence, the recommended dose and expected side effects are under debate. As an alternative solution, we proposed a newer hypothesis using the selective, potent anti-HIV drugs and flavonoid class of phytochemicals in combination to balance the potency and toxicity to combat against SARS-CoV-2. Primarily, ten anti-HIV protease inhibitor drugs with ten phyto-flavonoids selected as ligands for docking study against the putative target, the main protease (Mpro) of SARS-CoV-2 (PDB 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. The interchanged blind double-docking study suggested that ‘darunavir-quercetin-3-rhamnoside’ was the most potent and less toxic drug chemical-cocktail against SARS-CoV-2-Mpro. Mainly, the combined ‘anti-HIV drug and phyto-flavonoid’ was actively interacted with eight strong H-bond against SARS-CoV-2-Mpro and maintained their stability from analyzed RMRD-, RMSF- Rg-plots and MM/PBSA-binding energy during 100ns, which is more potential and consistent than individual. Thus, proposed docking-simulation based active and lesser toxic ‘anti-HIV-drug-phyto-flavonoid’ therapy could be promoted against SARS-CoV-2.

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This is an abstract of a preprint hosted on a preprint server, which is currently undergoing peer review at Scientific Reports. The findings have yet to be thoroughly evaluated, nor has a decision on ultimate publication been made. Therefore, the results reported should not be considered conclusive, and these findings should not be used to inform clinical practice, or public health policy, or be promoted as verified information.

Scientific Reports

Nature Research, Springer Nature