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

Abstract

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.

Photodynamic Inactivation of SARS-CoV-2 Infectivity and Antiviral Treatment Effects In Vitro

“…Here, it is conceivable that an oxidative modification, e.g., of theSARS-CoV-2 spike protein, occurs comparably quickly and might therefore inhibit receptor recognition and the cell membrane fusion process [35] Consistent with this idea, it was reported that the high susceptibility of viruses to PDI is not only caused by reduced structural integrity of viral RNA and virion membranes, but by loss of their surface glycoproteins, leading to non-infectious "bald" virions [18]. Since SARS-CoV-2 requires an envelope homotrimeric spike glycoprotein (S) to interact with the cellular receptor ACE-2 [36], it was proposed that selective impairment of surface proteins, like spike glycoprotein (S), by PDI can effectively inhibit infectivity of SARS-CoV-2 [24,25,37]. Additionally, it was suggested that effectivity of antiviral PDI may, in part, be explained by a light-induced photocleavage reaction of viral ssRNA [38].…”

In silico repurposed drugs against monkeypox virus

“…It can induce photo-cytotoxicity [64] and has been touted as a potential treatment and detection of cancer [63]. The photosensitising effects of hypericin has also shown efficacy of it being a multimodal antiviral [65], and has been long-known to inactivate murine cytomegalovirus (MCCV) and HIV-1, especially with exposure to fluorescent light [66].…”

“…It can induce photo-cytotoxicity [64] and has been touted as a potential treatment and detection of cancer [63]. The photosensitising effects of hypericin has also shown efficacy of it being a multimodal antiviral [65], and has been long-known to inactivate murine cytomegalovirus (MCCV) and HIV-1, especially with exposure to fluorescent light [66]. However, the use of St. John's Wort, by extension hypericin, in combination with other medicines, has previously proven an antagonistic effect [67] and could interfere with contraceptives [68].…”

Hypericin as a promising natural bioactive naphthodianthrone: A review of its pharmacology, pharmacokinetics, toxicity, and safety

“…Several studies provided evidence that Hyp exhibits potent antiviral activity when against SARS-CoV-2 (Islam et al, 2021;Mohamed et al, 2022). Besides its potent affinity for viral envelope (Delcanale et al, 2022) involves Mpro, RdRp, and 3Clpro (Mahmoudi et al, 2021;Matos et al, 2022).…”

“…Several studies provided evidence that Hyp exhibits potent antiviral activity when against SARS‐CoV‐2 (Islam et al, 2021; Mohamed et al, 2022). Besides its potent affinity for viral envelope (Delcanale et al, 2022), both Rocha et al and Mahmoudi et al indicated that Hyp could inhibit some specific viral proteins related to many distinct stages of the virus replication cycle in vitro, which involves Mpro, RdRp, and 3Clpro (Mahmoudi et al, 2021; Matos et al, 2022).…”