3-Hydroxyphthaloyl beta-lactoglobulin. III. Antiviral activity against herpesviruses.
The spread of sexually transmitted diseases, including human immunodeficiency virus type 1 (HIV-1) and herpesvirus infections, has continued unabated despite educational efforts spearheaded as a response to the HIV-1 epidemic. This suggests the need for prophylactic measures, including the application of topical antiviral agents. Chemical modification of bovine beta-lactoglobulin (beta-LG), the major protein of whey, by hydroxyphthalic anhydride (3HP) led to the generation of a potent HIV-1 inhibitor (designated 3HP-beta-LG) shown to also have activity against herpes simplex virus types 1 and 2 (HSV-1, HSV-2). This report provides more detailed results concerning the anti-herpesvirus activity of 3HP-beta-LG, indicating that this compound: (i) inhibited infection by human cytomegalovirus (HCMV), which is known to be sexually transmitted; (ii) inactivated the infectivity of both HSV-1 and HSV-2; (iii) inhibited cell-to-cell transmission of HSV-1 and HSV-2; and (iv) bound to HSV-1, HSV-2 and HCMV virus particles and partially inhibited the binding of anti-glycoprotein E (gE) and anti-gC monoclonal antibodies to HSV-1 and HSV-2. The binding of 3HP-beta-LG to the herpesviruses under study was inhibited by aggregated human IgG, suggesting that the respective viral Fc receptor is one of the target sites for 3HP-beta-LG. In agreement with results on inhibition of HIV-1 infection, 3HP-beta-LG appears to be the acid anhydride-modified protein of choice as an antiviral agent against herpesviruses.
Neurath
A R
AR
Lindsley F Kimball Research Institute of the New York Blood Center, New York, NY 10021, USA.
Strick
N
N
Li
Y Y
YY
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D004797:Enzyme-Linked Immunosorbent Assay; D006564:Herpesviridae / Q000187:drug effects*; D006801:Humans; D007782:Lactoglobulins / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests
C098082:3-hydroxyphthalic-beta-lactoglobulin; D000998:Antiviral Agents; D007782:Lactoglobulins