molecules of the month

Harnessing a novel mechanism for HIV eradication with a new class of bifunctional molecules. Modern antiretroviral therapies (ARTs) efficiently block HIV-1 replication, but are not completely curative because they can’t deplete viral reservoirs hidden from the immune system within the host genome. PYR01 is an HIV antiviral which, unlike traditional HIV drugs, is able to selectively kill HIV-1-infected cells that serve as cure-preventing viral reservoirs, in addition to the early-stage antiviral activity. This non-nucleoside reverse transcriptase inhibitor (NNRTI) is able to accomplish this through optimized potency for a secondary allosteric glue function that promotes dimerization of reverse transcriptase (RT), premature intracellular HIV-1 protease activation, cleavage and activation of host proteins including the CARD8 inflammasome, ultimately leading to pyroptotic cell death.…