Researchers, led by Yoshitsugu Ohata, identified a novel non-catalytic site integrase inhibitor (NCINI), JTP-0157602, with an original scaffold, and examined its strength as a allosteric human immunodeficiency virus (HIV)-1 integrase (IN) inhibitor. According to the researchers’ report, published in the Journal of Virology, JTP-0157602 exhibited strong antiviral activity and yielded responses comparable to the FDA-approved IN strand transfer inhibitors (INSTIs).
The study’s authors suggested that JTP-0157602, and similar compounds, could be used to treat HIV-1 infectious diseases, and laid out the expectation that NCINIs are potentially a new class of antiretrovirals, which may likely be developed and implemented in the treatment of HIV-1.
Ohata and colleagues reported that JTP-0157602 was fully effective against a “wide range of recombinant viruses with IN polymorphisms, including amino acids 124/125.” Furthermore, the novel NCINI maintained its antiviral effects against a broad panel of recombinant viruses with INSTI-related resistant mutations. Resistance selection experiments led the researchers to identify the A128T and T174I mutations. They also noted that JTP-0157602 primarily inhibited HIV-1 replication during the late-phase of the replication cycle, and “HIV-1 virions produced by reactivation from HIV-1 latently-infected Jurkat cells in the presence of JTP-0157602 were non-infectious.”
Overall, the authors concluded that their novel NCINI agent demonstrated highly favorable efficacy and resistance profiles, even maintaining its effectiveness against viral mutations resistant to standard INSTI treatments. Their data, and other emerging studies on NCINIs, support the further development of this potential new class of treatments for people living with HIV.
Source: Journal of Virology