Discovery of broad-spectrum antiviral activity in Amaryllidaceae alkaloids.

RNA virus infections pose a serious threat to public health, underscoring the need for broad-spectrum antiviral agents. In this study, we screened 383 plant-derived natural products with distinctive and structurally unique frameworks. We identified three Amaryllidaceae alkaloids, haemanthamine, crinamine, and 6-hydroxycrinamine, that exhibited inhibitory activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Vero E6/TMPRSS2 cells. Notably, these compounds concentration-dependently inhibited the replication of not only SARS-CoV-2 but also encephalomyocarditis virus, Sindbis virus, vesicular stomatitis virus, and influenza A virus, with antiviral activity distinguishable from cytotoxicity. These results suggest that Amaryllidaceae alkaloids possess broad-spectrum antiviral activity and are promising candidates for future antiviral drug development.