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 (Mpro) 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-Mpro. 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.