Biphenyl Furanocoumarin Compounds Inhibit SARS-CoV-2 Spike Pseudovirus Infection by Binding ACE2

The Corona Virus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), is a highly contagious disease that has posed a significant threat to global public health safety. Effective anti-drugs are urgently needed. In this study, based on the membrane chromatography (CMC) model of HEK293T overexpression of angiotensin-converting enzyme 2 (ACE2), six biphenyl furanocoumarin compounds with long retention time on ACE2h-CMC have been screened from the biphenyl furanocoumarin compounds synthesized in our group. The binding properties of the selected compounds to ACE2 were analyzed by frontier analysis. Cytotoxicity assay, pseudovirus invasion assay, and virtual molecular docking assay were used to detect the selected compounds' affinity and potential antiviral activity for ACE2 protein. The results showed that the biphenyl furanocoumarin BU-1, BU-2, and BU-5 could significantly inhibit the entry of SARS-COV-2 pseudoviruses into ACE2h cells. Virtual molecular docking results showed that BU-1, BU-2, and BU-5 could form evident hydrogen bonds with hot-pot amino acid residues on the ACE2 receptor. BU-1, BU-2, and BU-5 can be further modified as lead compounds to develop more effective anti-SARS-CoV-2 drugs. We hope that this work will contribute to developing anti-COVID-19 drugs and control COVID-19's epidemic situation.