Anticoronavirus Isoquinoline Alkaloids: Unraveling the Secrets of Their Structure–Activity Relationship

This study evaluates the antiviral activity of isoquinoline and Amaryllidaceae-type alkaloids against coronaviruses, focusing on their structure–activity relationships. Using Huh7 cancer cells and a lentivirus-based SARS-CoV-2 entry assay, several alkaloids, including haemanthidine, aromoline, and berbamine, showed significant protective effects against human coronavirus 229E. Aromoline was particularly potent against SARS-CoV-2 variants, suggesting its potential as a pan-coronavirus entry inhibitor. The study highlights the favorable safety profiles and drug-like properties of these alkaloids, suggesting their potential for therapeutic development against COVID-19. Molecular docking studies indicate that these compounds interact with the SARS-CoV-2 S-protein, inhibiting virus entry into host cells.