The Cholestanol-Conjugated Sulfated Oligosaccharide PG545 Disrupts the Lipid Envelope of Herpes Simplex Virus Particles

• Herpes simplex virus (HSV) and many other viruses including HIV initiate infection of host cells by binding to glycosaminoglycan (GAG) chains of cell surface proteoglycans. Although GAG mimetics such as sulfated oligo- and polysaccharides exhibit potent antiviral activity in cultured cells, the prophylactic application of these inhibitors as vaginal microbicides failed to protect women on their exposure to HIV infection. A possible explanation for this failure is that sulfated oligo- and polysaccharides exhibit no typical virucidal activity as their interaction with viral particles is largely electrostatic and reversible, and thereby vulnerable to competition with GAG-binding proteins of genital tract. Here we report that the cholestanol-conjugated sulfated oligosaccharide PG545, but not several other sulfated oligosaccharides lacking this modification, exhibited virucidal activity manifested as disruption of the lipid envelope of HSV-2 particles. Significance of the virus particle-disrupting activity of PG545 was also documented in experimental animals, as this compound in contrast to unmodified sulfated oligosaccharide protected mice against genital infection with HSV-2. Thus, PG545 offers a novel prophylaxis option against infections caused by GAG-binding viruses.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Infektionsmedicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Infectious Medicine (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

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