Nat Med breakthrough: discovery of an effective and long-term HIV inhibitor

September 17, 2019 / bioun / -- people living with HIV (PLWH) are worried about the life-long burden and stigma of daily medication As they may experience drug fatigue, it may lead to poor treatment compliance and drug-resistant virus variation, thus limiting future treatment options As a result, there is a strong interest in long-acting antiretroviral drugs (ARV) because of their low frequency of use For this reason, Stephen R Yant and his colleagues, together with collaborators from the University of Utah School of medicine and the University of Massachusetts School of medicine, reported a new small molecule HIV capsid inhibitor, gs-ca1, which has special effects on HIV-2 and all major HIV-1 types, including virus variants that are resistant to antiretroviral drugs currently in clinical use Photo source: Nature Medicine researchers have studied the mechanism of action of gs-ca1, which shows that gs-ca1 can directly bind to HIV-1 capsid, interfering with capsid mediated nuclear transfer of viral DNA, production of HIV particles and orderly capsid assembly The researchers found that the inappropriately selected variant capsid resistant to gs-ca1 in vitro was still completely sensitive to other types of ARVs Gs-ca1 has high metabolic stability and low solubility, which can make the drug release continuously in mice Therefore, it has a better antiviral effect only by subcutaneous administration In a humanized mouse model infected with HIV-1, the researchers found that gs-ca1, as a long-term single drug injection therapy, showed a high antiviral effect, and its effect was better than that of long-term ribavirin All in all, these results indicate the potential of strong capsid inhibitors as new long-acting drugs for HIV-1 infection Reference: Stephen R Yant et al A high potent long-acting small-molecular HIV-1 capsid inhibitor with efficient in a humanized mouse model Nature medicinevolume 25, pages 1377-1384 (2019) DOI https://doi.org/10.1038/s41591-019-0560-x