9PGS

HIV Capsid Hexamer bound to Compound 6

This is a non-PDB format compatible entry.

Summary for 9PGS

• Entry DOI: 10.2210/pdb9pgs/pdb
• Descriptor: HIV-1 capsid, 3,5-difluoro-Nalpha-[(5-hydroxy-1H-indol-3-yl)acetyl]-N-(4-methoxyphenyl)-N-methyl-L-phenylalaninamide (3 entities in total)
• Functional Keywords: capsid, p24, hiv-1, viral protein
• Biological source: Human immunodeficiency virus 1
• Total number of polymer chains: 12
• Total formula weight: 313031.65

Authors

Somoza, J.R.,Anderson, R.L.,Villasenor, A.G.,Ferrao, R.D. (deposition date: 2025-07-08, release date: 2025-10-08, Last modification date: 2025-10-29)

Primary citation

Canales, E.,Tse, W.,Schroeder, S.D.,Chou, C.H.,Liu, Q.,Zhang, J.,Lazerwith, S.E.,Morganelli, P.,Saito, R.D.,Brizgys, G.,Li, J.,Wu, Q.,Graupe, M.,Halcomb, R.L.,Desai, M.,Cannizzaro, C.,Hu, E.,Perry, J.K.,Villasenor, A.G.,Somoza, J.R.,Ferrao, R.D.,Swaminathan, S.,Zheng, J.,Lu, B.,Mwangi, J.,Wang, K.,Subramanian, R.,Smith, B.J.,Rhodes, G.,Rowe, W.,Sauer, D.,Lad, L.,Papalia, G.A.,Clancy, S.,Stepan, G.J.,Yu, H.,Sakowicz, R.,Shi, B.,Carr, G.,Bam, R.A.,Tsai, L.K.,Singer, E.,Hansen, D.,Mulato, A.,Yant, S.R.,Cihlar, T.,Link, J.O.
Discovery of Lenacapavir: First-in-Class Twice-Yearly Capsid Inhibitor for HIV-1 Treatment and Pre-exposure Prophylaxis.
J.Med.Chem., 68:21072-21094, 2025

PubMed Abstract: The HIV capsid is essential to the virus lifecycle, making it a promising target for therapeutic intervention. In 2006, a screening campaign was initiated to identify small molecules capable of disrupting the protein-protein interactions required for self-assembly of the 1500 capsid monomers that form the 37 MDa fullerene cone-shaped capsid. Numerous compound design cycles over many years were undertaken to discover the complex structural elements that together afford the multistage HIV capsid inhibitor lenacapavir. Lenacapavir is the most potent (HIV-1 EC = 105 pM) and longest-acting HIV antiviral to date, with a unique twice-yearly dosing regimen. Clinically, lenacapavir has demonstrated robust efficacy for both HIV-1 treatment and prevention, and, remarkably, achieved 100% protection in women for the first time. These findings represent a significant advancement in treatment and prevention of HIV-1 infection, offering the potential to profoundly impact the global course of the HIV epidemic.

PubMed: 41032707
DOI: 10.1021/acs.jmedchem.5c01625

Experimental method

X-RAY DIFFRACTION (2.4 Å)