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Azvudine + CL-197 is a combination drug under development, primarily as a potential long-acting, all-oral treatment for HIV-1 infection. Azvudine is a nucleoside reverse transcriptase inhibitor (NRTI) and a viral infectivity factor (Vif) inhibitor, demonstrating a dual mechanism of action against HIV-1. It is metabolized intracellularly into an active triphosphate form that causes chain termination upon incorporation into viral DNA, thereby inhibiting reverse transcriptase. Additionally, Azvudine inhibits Vif, which allows the host's APOBEC3G protein to induce hypermutation in viral DNA, rendering the virus non-infectious. Azvudine also functions as an RNA-dependent RNA polymerase (RdRp) inhibitor, particularly against SARS-CoV-2. CL-197 is also a nucleoside reverse transcriptase inhibitor (NRTI), specifically characterized as a translocation-defective reverse transcriptase inhibitor (TDRTI). Its active triphosphate form, once incorporated into the viral DNA chain, sterically hinders the translocation of reverse transcriptase, effectively halting further DNA synthesis. Developed by Genuine Biotech Limited, the combination aims to leverage the distinct yet complementary mechanisms of both compounds to enhance viral suppression, prevent drug resistance, and offer a convenient weekly oral dosing regimen for HIV-1 patients.
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