In silico investigation on the inhibitory effect of fungal secondary metabolites on RNA dependent RNA polymerase of SARS-CoV-II: A docking and molecular dynamic simulation study

Ebrahimi, Kosar Sadat; Ansari, Mohabbat; Hosseyni Moghaddam, Mahdieh S; Ebrahimi, Zohre; salehi, Zohre; Shahlaei, Mohsen; Moradi, Sajad

The newly emerged Coronavirus Disease 2019 (COVID-19) rapidly outspread worldwide and now is one of the biggest infectious pandemics in human society. In this study, the inhibitory potential of 99 secondary metabolites obtained from endophytic fungi was investigated against the new coronavirus RNA-dependent RNA polymerase (RdRp) using computational methods. A sequence of blind and targeted molecular dockings was performed to predict the more potent compounds on the viral enzyme. In the next step, the five selected compounds were further evaluated by molecular dynamics (MD) simulation. Moreover, the pharmacokinetics of the metabolites was assessed using SwissADME server. The results of molecular docking showed that compounds 18-methoxy cytochalasin J, (22E,24R)-stigmasta-5,7,22-trien-3-β-ol, beauvericin, dankasterone B, and pyrrocidine A had higher binding energy than others. The findings of MD and SwissADME demonstrated that two fungal metabolites, 18-methoxy cytochalasin J and pyrrocidine A had better results than others in terms of protein instability, strong complex formation, and pharmacokinetic properties. In conclusion, it is recommended to further evaluate the compounds 18-methoxy cytochalasin J and pyrrocidine A in the laboratory as good candidates for inhibiting COVID-19.