OBJECTIVE: Since no effective therapy exists, we aimed to test existing HIV antivirals for combination treatment of Coronavirus disease 19 (COVID-19). MATERIALS AND METHODS: The crystal structures of SARS-CoV-2 main protein (Mpro) (PDB ID: 6Y2F) and SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) (PDB ID: 7BV2) both available from Protein Data Bank were used in the study. Automated Docking by using blind and standard method both on Mpro and RdRp bound to the modified template-primer RNA was performed with AutoDock 4.2.6 program suite. Lamarckian genetic algorithm (LGA) was used for structures docking. All inhibitors were docked with all bonds completely free to rotate. RESULTS: Our molecular docking findings suggest that lopinavir, ritonavir, darunavir, and atazanavir activated interactions with the key binding sites of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) protease with a better inhibition constant (Ki) for lopinavir, ritonavir, and darunavir. Furthermore, we evidenced the ability of remdesivir, tenofovir, emtricitabine, and lamivudine to be incorporated in SARS-CoV-2 RdRp in the same protein pocket where poses the corresponding natural nucleoside substrates with comparable Ki and activating similar interactions. In principle, the four antiviral nucleotides might be used effectively against SARS-CoV-2. CONCLUSIONS: The combination of a protease inhibitor and two nucleoside analogues, drugs widely used to treat HIV infection, could be evaluated in clinical trials for the treatment of COVID-19.
OBJECTIVE: Since no effective therapy exists, we aimed to test existing HIV antivirals for combination treatment of Coronavirus disease 19 (COVID-19). MATERIALS AND METHODS: The crystal structures of SARS-CoV-2 main protein (Mpro) (PDB ID: 6Y2F) and SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) (PDB ID: 7BV2) both available from Protein Data Bank were used in the study. Automated Docking by using blind and standard method both on Mpro and RdRp bound to the modified template-primer RNA was performed with AutoDock 4.2.6 program suite. Lamarckian genetic algorithm (LGA) was used for structures docking. All inhibitors were docked with all bonds completely free to rotate. RESULTS: Our molecular docking findings suggest that lopinavir, ritonavir, darunavir, and atazanavir activated interactions with the key binding sites of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) protease with a better inhibition constant (Ki) for lopinavir, ritonavir, and darunavir. Furthermore, we evidenced the ability of remdesivir, tenofovir, emtricitabine, and lamivudine to be incorporated in SARS-CoV-2RdRp in the same protein pocket where poses the corresponding natural nucleoside substrates with comparable Ki and activating similar interactions. In principle, the four antiviral nucleotides might be used effectively against SARS-CoV-2. CONCLUSIONS: The combination of a protease inhibitor and two nucleoside analogues, drugs widely used to treat HIV infection, could be evaluated in clinical trials for the treatment of COVID-19.