Betulinic Acid-Derived HIV-1 Maturation Inhibitors: Bridging Chemical Design, Molecular Dynamics, and Experimental Evidence
4 affiliations
- 1Department of General and Biological Chemistry, Astana Medical University, Astana 010000, Kazakhstan
- 2School of Pharmacy, Astana Medical University, Astana 010000, Kazakhstan
- 3Department of Pharmaceutical Disciplines, Astana Medical University, Astana 010000, Kazakhstan
- 4Department of Organization, Management and Economics of Pharmacy and Clinical Pharmacy, Asfendiyarov Kazakh National Medical University, Almaty 050012, Kazakhstan
Abstract
Betulinic acid-derived human immunodeficiency virus type 1 (HIV-1) maturation inhibitors connect natural-product medicinal chemistry with inhibition of capsid–spacer peptide 1 (CA–SP1) processing. This critical narrative review examines how chemical modifications relate to target structure, conformational dynamics, antiviral activity and development limitations. C-3 pharmacophore replacement and modification of the C-28/C-17 region improved antiviral breadth and exposure, but improved cellular potency alone did not establish clinical differentiation. Cryo-electron microscopy, microcrystal electron diffraction and nuclear magnetic resonance support engagement of the CA–SP1 six-helix bundle and restriction of its dynamics. Molecular simulations offer an ensemble-based explanation whose interpretation depends on assembly state, cofactors, sampling and experimental validation. Binding kinetics and cleavage measurements provide particularly informative connections between molecular observations and antiviral activity. Later-generation compounds demonstrate that broader susceptibility coverage and favorable pharmacokinetics must be evaluated alongside tolerability, resistance and regimen requirements. Progress therefore depends on aligning compound identity, relevant target assemblies, experimentally constrained dynamics, and functional processing and exposure, while retaining negative and discordant findings.
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BibTeX
@article{sapiyeva2026betulinic,
title = {{Betulinic Acid-Derived HIV-1 Maturation Inhibitors: Bridging Chemical Design, Molecular Dynamics, and Experimental Evidence}},
author = {Ardak Sapiyeva and Nurlan Sadykov and Aziza Omari and Karlygash Akpayeva and Galiya Aipova and Kairat S. Zhakipbekov},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219509},
url = {https://www.mdpi.com/1422-0067/27/21/9509},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Betulinic Acid-Derived HIV-1 Maturation Inhibitors: Bridging Chemical Design, Molecular Dynamics, and Experimental Evidence
AU - Ardak Sapiyeva
AU - Nurlan Sadykov
AU - Aziza Omari
AU - Karlygash Akpayeva
AU - Galiya Aipova
AU - Kairat S. Zhakipbekov
PY - 2026
DA - 2026/10/24
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219509
UR - https://www.mdpi.com/1422-0067/27/21/9509
AB - Betulinic acid-derived human immunodeficiency virus type 1 (HIV-1) maturation inhibitors connect natural-product medicinal chemistry with inhibition of capsid–spacer peptide 1 (CA–SP1) processing. This critical narrative review examines how chemical modifications relate to target structure, conformational dynamics, antiviral activity and development limitations. C-3 pharmacophore replacement and modification of the C-28/C-17 region improved antiviral breadth and exposure, but improved cellular potency alone did not establish clinical differentiation. Cryo-electron microscopy, microcrystal electron diffraction and nuclear magnetic resonance support engagement of the CA–SP1 six-helix bundle and restriction of its dynamics. Molecular simulations offer an ensemble-based explanation whose interpretation depends on assembly state, cofactors, sampling and experimental validation. Binding kinetics and cleavage measurements provide particularly informative connections between molecular observations and antiviral activity. Later-generation compounds demonstrate that broader susceptibility coverage and favorable pharmacokinetics must be evaluated alongside tolerability, resistance and regimen requirements. Progress therefore depends on aligning compound identity, relevant target assemblies, experimentally constrained dynamics, and functional processing and exposure, while retaining negative and discordant findings.
SN - 1422-0067
ER -