![]() ![]() contributed to reviewing and editing of the manuscript. were responsible for writing the original draft of the manuscript. performed experiments with cells from PLWH using the Simoa assay. performed cellular antiviral and TACK assays. The best way to think about using Jmol is to imagine what you would actually like to do, then figure out which scripting commands fit your purpose. T.L.D., Z.F., M.L., M.X., L.B., J.F.F., and S.L.G. Jmols seemingly endless list of commands can make it seem like a daunting tool to learn. TACK molecules retain potent antiviral activity and selectively eliminate infected CD4 + T cells isolated from people living with HIV-1, supporting an immune-independent clearance strategy. These targeted activator of cell kill (TACK) molecules bind the reverse transcriptase–p66 domain of monomeric Gag-Pol and act as allosteric modulators to accelerate dimerization, resulting in HIV-1 + cell death through premature intracellular viral protease activation. Focusing on this secondary activity, we found bifunctional compounds with HIV-1–infected cell kill potency at clinically achievable concentrations. Some HIV-1 nonnucleoside reverse transcriptase inhibitors induce HIV-1 selective cytotoxicity in vitro but require concentrations far exceeding approved dosages. Reservoir reduction is therefore an important HIV-1 cure strategy. Howell, and Antonella Converso +27 authors +25 authors +20 authors fewer Authors Info & AffiliationsĪntiretroviral therapy inhibits HIV-1 replication but is not curative due to establishment of a persistent reservoir after virus integration into the host genome. Rosenbloom, Payal Sheth, Deping Wang, Guoxin Wu, Matthias Zebisch, Tian Zhao, Paul Zuck, Jay Grobler, Daria J. Fay, Ashley Forster, Shih Lin Goh, Meigang Gu, Daniel Krosky, Daniel I. S. Carroll, Abdellatif El Marrouni, John F. Cheney, Jan Kristoff, Meiqing Lu, Marina Bukhtiyarova, , Yangsi Ou, Min Xu, Lei Ba, Steven S. ![]()
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