# Anti-HIV-1 Activity of the Integrase Strand Transfer Inhibitor ACC017

## TL;DR

ACC017 is a new HIV-1 drug that effectively stops the virus from integrating into human cells, even against drug-resistant strains.

## Contribution

ACC017 is a novel INSTI with potent anti-HIV-1 activity and resistance profile distinct from existing drugs.

## Key findings

- ACC017 showed potent activity against HIV-1IIIB with an EC50 of 0.59 nM.
- It remained effective against drug-resistant and clinical HIV-1 strains.
- Resistance selection produced D232N and R263K mutations but not G140 or Q148 variants.

## Abstract

HIV-1 integrase strand transfer inhibitors (INSTIs) are pivotal to antiretroviral therapy. However, the emergence of drug-resistant mutations necessitates the development of new agents. Here, we present ACC017 as a novel INSTI candidate. ACC017 demonstrated potent activity against the laboratory-adapted HIV-1IIIB strain (EC50 = 0.59 nM; SI > 34,525) and maintained efficacy against a panel of drug-resistant strains (EC50 range from 0.34 to 9.12 nM) and clinical isolated strains (EC50 range from 0.11 to 1.78 nM). Mechanism of action studies confirmed its ability to inhibit the integrase enzyme (IC50 = 9.19 nM) and effectively block viral genome integration. Notably, in vitro resistance selection primarily yielded D232N and R263K mutations, without the emergence of G140S/A/C/R or Q148H/R/K. This promising profile, combined with synergistic interactions with other antiretroviral drugs, positions ACC017 as a potential therapeutic option.