Computation screening and Molecular Docking of FDA approved viral protease inhibitors as a potential drug against COVID-19
Gastroenterology and Hepatology from Bed to Bench,
20 September 2020
Aim: This study demonstrated potent inhibitors against COVID-19 using molecular docking approach of FDA approved viral antiprotease drugs.
Background: The COVID-19 has now been spread to throughout world. There is serious need of finding potential therapeutic agents. The 3C-like protease (Mpro/6LU7) has an attractive molecular target for rational anti-CoV drugs.
Methods: The tertiary structure of COVID-19 Mpro obtained from protein data bank repository and molecular docking screening was performed by Molegro Virtual Docker Ver.6 with grid resolution of 0.30 Å. Docking scores (DOS) are representative of calculated ligand-receptor (protein) interaction energy; therefore, more negative scores mean better binding tendency. After that, we applied another docking study on each of selected drugs with best ligands separately and using a more accurate RMSD algorithm.
Result: Docking results of COVID-19 major protease (6LU7) with selected 4 FDA approved viral antiprotease drugs (Temoporfin, Simeprevir, Cobicistat, Ritonavir) out of the selected 17 showed best docking score. Out of the 4 compounds, Temoporfin exhibited the best DOS (-202.88) and the best screened ligand with COVID-19 Mpro, followed by Simeprevir (-201.66), Cobicistat (-187.75), and Ritonavir (-186.66). Temoporfin as the best screened ligand could target the Mpro with 20 different conformations, while Simeprevir, Cobicistat, and Ritonavir make 14, 10 and 10 potential conformations at the binding site, respectively.
Conclusions: Our findings showed that selected four FDA approved drugs can be potent inhibitors against COVID-19, however among them, the use of Temoporfin medication may be more potent for the treatment of the disease. Based on the findings, we recommend in-vitro and in-vivo evaluations to determine their effectiveness against COVID-19.
- Abstract Viewed: 0 times