Journal
SCIENCE
Volume 370, Issue 6514, Pages 360-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abb4808
Keywords
-
Categories
Funding
- NIH [R01 AI062520, R01 AI143649, R01 AI157802, U54 AI150472, R01 AI129862, R01 AI052014, R01 AI77344, DP1 DA043915]
Ask authors/readers for more resources
The potent HIV-1 capsid inhibitor GS-6207 is an investigational principal component of long-acting antiretroviral therapy. We found that GS-6207 inhibits HIV-1 by stabilizing and thereby preventing functional disassembly of the capsid shell in infected cells. X-ray crystallography, cryo-electron microscopy, and hydrogen-deuterium exchange experiments revealed that GS-6207 tightly binds two adjoining capsid subunits and promotes distal intra- and inter-hexamer interactions that stabilize the curved capsid lattice. In addition, GS-6207 interferes with capsid binding to the cellular HIV-1 cofactors Nup153 and CPSF6 that mediate viral nuclear import and direct integration into gene-rich regions of chromatin. These findings elucidate structural insights into the multimodal, potent antiviral activity of GS-6207 and provide a means for rationally developing second-generation therapies.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available