5ZPW

Generation of a long-acting fusion inhibitor against HIV-1

Summary for 5ZPW

• Entry DOI: 10.2210/pdb5zpw/pdb
• Descriptor: Transmembrane protein gp41, MET-THR-TRP-GLU-GLU-TRP-ASP-MK8-LYS-ILE-GLU-MK8-TYR-THR-MK8-LYS-ILE-GLU-MK8-LEU-ILE-LYS-LYS-SER (3 entities in total)
• Functional Keywords: inhibitor, complex, virus, virus like particle
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 6
• Total formula weight: 21652.94

Authors

Guo, Y.,Shi, X.L. (deposition date: 2018-04-16, release date: 2019-03-06, Last modification date: 2024-10-16)

Primary citation

Guo, Y.,Zhou, P.P.,Zhang, S.Y.,Fan, X.W.,Dou, Y.W.,Shi, X.L.
Generation of a long-acting fusion inhibitor against HIV-1.
Medchemcomm, 9:1226-1231, 2018

PubMed Abstract: AIDS has evolved from a fatal infectious disease to a manageable chronic disease under the treatment of anti-AIDS medications. HIV fusion inhibitors with high activity, low side effects and strong selectivity are promising drugs against HIV. Only one fusion inhibitor is currently approved, thereby highly active long-acting fusion inhibitors need to be developed for long-term AIDS treatment. Here, we synthesised MT-SC22EK (a small HIV fusion inhibitor) derivatives containing 1-2 staples to improve its stability. Antiviral activity studies showed that MT-SC22EK-2 with two staples exhibited potent inhibitory activity against HIV-1 standard strains and Chinese epidemic strains, and at the same time, MT-SC22EK-2 presented strong anti-T20 resistance. Surprisingly, MT-SC22EK-2 possessed excellent protease stability with a half-life of 3665 min. MT-SC22EK-2 is a potential HIV fusion inhibitor considered as a long-acting anti-HIV drug candidate.

PubMed: 30109011
DOI: 10.1039/c8md00124c

Experimental method

X-RAY DIFFRACTION (2.199 Å)