The Interaction of Hypericin with SARS-CoV-2 Reveals a Multimodal Antiviral Activity

Hypericin is a photosensitizing drug that is active against membrane-enveloped viruses and therefore constitutes a promising candidate for the treatment of SARS-CoV-2 infections. The antiviral efficacy of hypericin is largely determined by its affinity toward viral components and by the number of active molecules loaded on single viruses. Here we use an experimental approach to follow the interaction of hypericin with SARS-CoV-2, and we evaluate its antiviral efficacy, both in the dark and upon photoactivation. Binding to viral particles is directly visualized with fluorescence microscopy, and a strong affinity for the viral particles, most likely for the viral envelope, is measured spectroscopically. The loading of a maximum of approximately 30 molecules per viral particle is estimated, despite with marked heterogeneity among particles. Because of this interaction, nanomolar concentrations of photoactivated hypericin substantially reduce virus infectivity on Vero E6 cells, but a partial effect is also observed in dark conditions, suggesting multiple mechanisms of action for this drug.

Automated summary

Hypericin, as a photosensitizing drug, shows promise in treating SARS-CoV-2 infections due to its antiviral activity against membrane-enveloped viruses. Experimental studies reveal the interaction of hypericin with SARS-CoV-2 and evaluate its antiviral efficacy. Hypericin exhibits a strong affinity for viral particles, particularly the viral envelope, and approximately 30 molecules can be loaded onto each viral particle. Photoactivated hypericin at nanomolar concentrations significantly reduces virus infectivity on Vero E6 cells, indicating potential multiple mechanisms of action for this drug.