Year: 2026
Type: article
Abstract: BACKGROUND: Protease (PR) inhibitors (PIs) are widely regarded as the most significant agents in the treatment of human immunodeficiency virus (HIV) and have been instrumental in the success of highly active antiretroviral therapy (HAART). The PR enzyme is essential for the viral life cycle, as it cleaves various polyproteins into the individual components necessary for the formation of mature, infectious virions. METHODS: We systematically synthesized current evidence which revealed the multifaceted effects of PIs, which can function as entry inhibitors, reverse transcription inhibitors and inhibitors of post-reverse transcription processes. RESULTS: All currently available PIs are confronted with the challenge of emerging drug-resistant viral strains, necessitating the exploration of novel PIs capable of overcoming this resistance. CONCLUSION: This review addresses the current landscape of PIs, the primary PR mutations that confer drug resistance, and identifies three classes of novel PIs that warrant consideration for anti-HIV drug development: (i) novel PIs exhibiting robust inhibitory activity that target the traditional active, non-active and cleavage sites of PR; (ii) novel PIs designed to target drug-resistant PR variants, particularly those associated with multi-drug resistant (MDR) HIV isolates; and (iii) novel PIs that engage multiple stages of HIV replication, thereby enhancing the anti-HIV efficacy of PIs.
Source: Annals of Medicine
Authors: Wan-Gang Gu, Gui-Zhen Yin, Yan-Peng Zhang
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,557
Funder: Gannan Medical University
OpenAlex ID: W7124950163