Avirulins may provide a valuable chemical basis for the development of the next generation of prophylactic drugs for HIV-1 in women, according to the results of a study presented at the American Society of Microbiology (ASM) Microbe 2019, held from June 20-24, 2019, in San Francisco, California.
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Although significant progress has been made in reducing the risk of HIV transmission and preventing mortality among people living with HIV, recent developments in antiretroviral drug resistance have created a new concern for this population. Specifically, there is concern for women at risk of HIV infection because few therapies are effective against the mucosal lining of the female genital tract.
Researchers screened a library of 2,095 small-molecule compounds to determine antiviral activity against the BaL strain of HIV-1 and identified several molecular representatives of unique antiviral activity against this strain. This led to the identification of a unique class of HIV-1 inhibitors that the researchers named avirulins.
The study researchers determined that avirulins were active against clinical HIV-1 isolates of genetic variant subtypes, including several types known to have decreased sensitivity to other antivirals. The avirulins showed dose-dependent inhibition of HIV-1 reverse transcriptase and were active against several strains resistant to nucleoside reverse transcriptase inhibitors and one strain resistant to non-nucleoside reverse transcriptase inhibitors. The researchers noted that this suggested a non-competitive mechanism of action.
The researchers noted that drugs that damage the female reproductive tract can increase the risk of HIV-1 transmission and therefore 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, the antiviral activity of avirulin was not diminished in human vaginal fluid, suggesting retained potency in the middle of the female reproductive tract.”
Reference
Cole AM, Cherne MD, Chong CF, Cole AL. Avirulins, a novel class of HIV-1 reverse transcriptase inhibitors, effective against HIV-1 in the mucosa of the female reproductive tract. Presented at: ASM Microbe 2019; June 20-24, 2019; San Francisco, California. Poster P437