HIV-1 reverse transcriptase (RT) and SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) (RT/RdRp)

Viral reverse transcriptase (RT) and RNA-dependent RNA polymerase (RdRp) are essential enzymes for the replication of retroviruses and RNA viruses, respectively. HIV-1 reverse transcriptase is responsible for converting the viral RNA genome into DNA, which is then integrated into the host cell's genome (Wang et al., 2014). SARS-CoV-2 RdRp, specifically the nsp12 subunit, catalyzes the synthesis of viral RNA from an RNA template, a process vital for the production of new viral particles (Zhang et al., 2021). Azvudine is a dual-target nucleoside analog that inhibits both of these enzymes. It is characterized by a 4'-azido and 2'-fluoro substitution, which provides high stability and potent inhibitory activity. By acting as a chain terminator, azvudine prevents the completion of viral genome replication, thereby reducing viral load and improving clinical outcomes in patients with HIV-1 or COVID-19 (Ren et al., 2022). It was the first home-grown anti-SARS-CoV-2 oral drug approved in China.

Other names

Reverse transcriptaseRNA-directed RNA polymerasensp12HIV-1 RTSARS-CoV-2 RdRpFNC

Azvudine is a nucleoside analog (2'-deoxy-2'-β-fluoro-4'-azidocytidine) that acts as a prodrug. Upon entering host cells, it is phosphorylated into its active triphosphate form (Azvudine-TP). This active metabolite competes with natural deoxynucleoside triphosphates (dNTPs) for incorporation into the nascent viral DNA (in HIV-1) or RNA (in SARS-CoV-2) chains. Due to the 4'-azido group, its incorporation leads to premature chain termination, effectively inhibiting the activity of HIV-1 reverse transcriptase and SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) (Zhang et al., 2021; Wang et al., 2014).