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  • Title: The effect of gramicidin, a topical contraceptive and antimicrobial agent with anti-HIV activity, against herpes simplex viruses type 1 and 2 in vitro.
    Author: Bourinbaiar AS, Coleman CF.
    Journal: Arch Virol; 1997; 142(11):2225-35. PubMed ID: 9672588.
    Abstract:
    The effect of an anti-HIV compound, gramicidin, previously used as a topical antibiotic and vaginal contraceptive, on the replication of herpes simplex viruses (HSV) type 1 and 2 has been examined. Human WI-38 fibroblasts were inoculated with either HSV type in the presence of serial dilutions of gramicidin and reduction in viral yield was measured by ELISA. The 50% inhibitory dose (IC50) of gramicidin against 3 HSV-1 and 4 HSV-2 isolates was equal to 0.3 microgram/ml and was comparable to the efficacy of the anti-HSV agent acyclovir (ACV). The IC50 of gramicidin required to protect WI-38 from cytolytic effect of HSV was 10 micrograms/ml at day 5 postinfection, indicating that at this time point the activity of gramicidin was inferior than that of ACV. Nevertheless, gramicidin suppressed the replication of ACV-resistant thymidine kinase and DNA polymerase HSV mutants at doses effective against ACV-sensitive strains. The results suggest that the antimicrobial and spermostatic agent, gramicidin, has potential against sexually transmitted diseases (STDs) and for prophylaxis of sex-borne HIV and HSV infections. Symptomatic human herpes simplex virus type 1 (HSV-1) infections are rather benign in immunocompetent individuals. The primary clinical manifestations of HSV-2 infection, which is mainly transmitted sexually, are anogenital lesions. Genital herpes affects one third of the world's population, and possibly 80% of those infected with HIV. HSV infections are especially severe and even life-threatening in people with AIDS. Only 20% of herpes seropositive persons have symptomatic infection, with the remainder asymptomatic but able to shed the virus. HSV infections are usually treated with nucleoside analogs such as acyclovir (ACV), but HSV eventually becomes resistant to ACV due to the loss or mutation of the viral thymidine kinase (TK) or changes in viral DNA polymerase. Gramicidin has recently been identified as a potent nontoxic anti-HIV agent 3-5 times more active than nonoxynol-9. Findings are reported from an assessment of the effect of gramicidin upon the replication of HSV-1 and HSV-2. Human WI-38 fibroblasts were inoculated with either HSV type in the presence of serial dilutions of gramicidin, while reduction in viral yield was measured by ELISA. The 50% inhibitory dose (IC50) of gramicidin against 3 HSV-1 and 4 HSV-2 isolates was equal to 0.3 mcg/ml and was comparable to the efficacy of ACV. The IC50 of gramicidin required to protect WI-38 from the cytolytic effect of HSV was 10 mcg/ml at day 5 postinfection, indicating that gramicidin was less active than ACV. Gramicidin nonetheless suppressed the replication of ACV-resistant thymidine kinase and DNA polymerase HSV mutants at doses effective against ACV-sensitive strains. These results suggest that gramicidin could be used against STDs and to prevent sexually transmitted HIV and HSV infections.
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