Virtual Screening of Chinese Medicine Small Molecule Compounds Targeting SARS-CoV-2 3CL Protease (3CL pro)

Background: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has attracted worldwide attention due to its high infectivity and pathogenicity. Objective: The purpose of this study is to develop drugs with therapeutic potentials for COVID-19. Methods: we selected the crystal structure of 3CL pro to perform virtual screening against natural products in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Then, molecular dynamics (MD) simulation was carried out to explore the binding mode between compounds and 3CL pro. Results and Discussion: A total of 6 candidates with good theoretical binding affinity to 3CL pro were identified. The binding mode after MD shows that hydrogen bonding and hydrophobic interaction play an important role in the binding process. Finally, based on the free binding energy analysis, the candidate natural product Gypenoside LXXV may bind to 3CL pro with high binding affinity. Conclusion: The natural product Gypenoside LXXV may have good potential anti-SARS-COV-2 activity.