Photodynamic inactivation of infectivity of human immunodeficiency virus and other enveloped viruses using hypericin and rose bengal: inhibition of fusion and syncytia formation.

Abstract

The mechanism of the antiviral activity of hypericin was characterized and compared with that of rose bengal. Both compounds inactivate enveloped (but not unenveloped) viruses upon illumination by visible light. Human immunodeficiency and vesicular stomatitis viruses were photodynamically inactivated by both dyes at nanomolar concentrations. Photodynamic inactivation of fusion (hemolysis) by vesicular stomatitis, influenza, and Sendai viruses was induced by both dyes under similar conditions (e.g., I50 = 20-50 nM for vesicular stomatitis virus), suggesting that loss of infectivity resulted from inactivation of fusion. Syncytium formation, between cells activated to express human immunodeficiency virus gpl20 on their surfaces and CD4+ cells, was inhibited by illumination in the presence of 1 ,uM hypericin. Hypericin and rose bengal thus exert similar virucidal effects. Both presumably act by the same mechanism-namely, the inactivation of the viral fusion function by singlet oxygen produced upon illumination. The implications of this photodynamic antiviral action for the potential therapeutic usefulness of both hypericin and rose bengal are discussed.

Reduction in hypericin-induced phototoxicity by Hypericum perforatum extracts and pure compounds

“…Aggressive analysis of this plant over the last three decades has revealed that it possesses several biological properties, including antidepressant, antiviral and antiproliferative activities [4][5][6][7][8]. Although H. perforatum (Hp) is most commonly used as an alternative to standard tricyclic antidepressants, other biological properties possessed by this plant have also been utilized for the treatment of cancer and viral infections [8][9][10][11][12].…”

“…In addition to these compounds, two very active classes of constituents unique to Hypericum have also been identified, the phloroglucinols, consisting primarily of hyperforin and adhyperforin and the naphthodianthrones, hypericin and pseudohypericin [1][2][3][4][5][6][7]. Biological activities and toxicities possessed by this plant may also depend on the properties of several constituents collectively provoking a variety of physiological responses.…”

Roles of Oxygen and Photoinduced Acidification in the Light-Dependent Antiviral Activity of Hypocrellin A

“…Hypocrellin has been used as a phototherapeutic agent for various skin diseases and tumors and has been taken orally as a folk medicine for several centuries in China (Diwu & Lown, 1990;Diwu et al, 1989). Like the related polycyclic quinone hypericin (Meruelo et al, 1988Degar et al, 1992;Lenard et al, 1993;Carpenter & Kraus, 1991), hypocrellin A possesses light-induced toxicity against the human immunodeficiency virus, HIV, and related viruses (Hudson et al, 1994). This common property of hypocrellin A and hypericin has led us to examine in more detail the similarities and differences between these chromophores.…”

“…Hypericin has a large triplet yield r0.70 in ethanol (Jardon et al, 1986)] and is capable of generating significant quantities of singlet oxygen (Meruelo et al, 1988Degar et al, 1992;Lenard et al, 1993). The virucidal activity of hypericin results, in part, from production of singlet oxygen.…”

Photodynamic treatment of adenoviral vectors with visible light: an easy and convenient method for viral inactivation

“…17,18 After phototreatment, both viruses showed cross-linking of viral membrane proteins, which are involved in this fusion. Although the use of uroporphyrin for virus inactivation has never been reported, the photodynamic effects of porphyrins, including uroporphyrin, on isolated cells, cell membranes, subcellular organelles and on proteins of cytosol and plasma have been investigated extensively.…”