ORIGINAL RESEARCH article
Front. Immunol.
Sec. Viral Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1648546
This article is part of the Research TopicDeciphering Host-Virus Interactions and Advancing Therapeutics for Chronic Viral InfectionView all 7 articles
HIV Subtype-Specific gp140-CD4 Binding, Temsavir Efficacy, and Identification of Novel Adhesion Inhibitors Against Chinese HIV Strains
Provisionally accepted
Tianyang Liu1Xiaowen Li2Xiaolin Yang1
Shengjie Zhang1Yao Wang3
SIwei Zhang1Shanshan Tang4
Fuxiang Wang1Yao Zhao1
Hongzhou Lu1
Lanlan Wei1*- 1Shenzhen Third People’s Hospital, Shenzhen, China
- 2Southern University of Science and Technology, Shenzhen, China
- 3Jiamusi University, Jiamusi, China
- 4The Affiliated Hospital of Southwest Medical University, Luzhou, China
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The human immunodeficiency virus (HIV) epidemic in China is characterized by marked genetic diversity with multiple circulating recombinant forms (CRFs). The gp120-CD4 interaction, essential for viral cellular entry, exhibits subtype-dependent structural variations that compromise therapeutic efficacy. While temsavir remains the sole FDA-approved adhesion inhibitor, its activity against predominant Chinese HIV subtypes is incompletely characterized. HIV subtyping of 472 clinical samples identified five major strains (B, CRF01_AE, CRF07_BC, CRF08_BC, and CRF55_01B). Recombinant gp140 proteins from these subtypes were expressed, purified, and analyzed via bio-layer interferometry (BLI), revealing subtype B as the strongest CD4 binder (KD=79 pM), while CRF55_01B exhibited the weakest interaction (KD=8.76 nM). Structural analyses demonstrated that CRF variants displayed reduced hydrogen bonding and smaller interface buried surface areas, correlating with diminished binding affinity. Temsavir showed subtype-dependent inhibition efficacy, achieving 35.7% inhibition for subtype B versus <1.3% for CRF01_AE/CRF55_01B, a disparity attributed to steric hindrance from the S375H mutation. Virtual screening of 13,819 compounds followed by BLI validation identified five novel CRF55_01B-targeting inhibitors with ≥19% inhibition rates. These findings elucidate structural determinants of HIV-1 adhesion variability and provide candidate inhibitors tailored for Chinese CRF subtypes, facilitating the development of region-specific therapeutic strategies.
Keywords: HIV-1, gp140-CD4 binding, Temsavir, CRF subtypes, adhesion inhibitors
Received: 17 Jun 2025; Accepted: 02 Sep 2025.
Copyright: © 2025 Liu, Li, Yang, Zhang, Wang, Zhang, Tang, Wang, Zhao, Lu and Wei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Lanlan Wei, Shenzhen Third People’s Hospital, Shenzhen, China
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