Avirulins may provide a valuable chemical foundation for the development of the next generation of prophylactic medications for HIV-1 in women, according to results of a study presented at American Society of Microbiology (ASM) Microbe 2019 held from June 20-24, 2019, in San Francisco, California.

Although much progress has been made in decreasing the risk for transmission of HIV and in the prevention of mortality in people living with HIV, recent developments in resistance to antiretroviral medications has created a new concern for people living with HIV. Specifically, there is concern for women at risk for HIV because few therapies are effective in the mucosa of the female genital tract.

Researchers screened a library of 2095 small molecule compounds for antiviral activity against the BaL strain of HIV-1 and identified several molecular representatives of a unique antiviral activity against this strain. This resulted in the identification of a unique class of HIV-1 inhibitors that researchers called avirulins.

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Study investigators determined that avirulins were active against clinical isolates of HIV-1 from genetically variant subtypes, including several types that have a known decrease in sensitivity to other antivirals. Avirulins showed a dose-dependent inhibition of the HIV-1 reverse transcriptase and were active against several nucleoside reverse transcriptase inhibitor-resistant strains and one nonnucleoside reverse transcriptase inhibitor-resistant strain. Researchers noted that this suggested a noncompetitive mechanism of action.

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Researchers highlighted that drugs that cause damage to the female reproductive tract can increase the risk for HIV-1 transmission and therefore they investigated the cytotoxicity of avirulins against epithelial cells derived from the female reproductive tract. They found no significant toxicity, even at the highest concentrations, and reported that “importantly, avirulin antiviral activity was not diminished in human vaginal fluid, suggesting retained potency in the milieu of the female reproductive tract.”


Cole AM, Cherne MD, Chong CF, Cole AL. Avirulins, a novel class of HIV-1 reverse transcriptase inhibitors HIV-1 effective in the female reproductive tract mucosa. Presented at: ASM Microbe 2019; June 20-24, 2019; San Francisco, California. Poster P437.