POZ Community Forums
Meds, Mind, Body & Benefits => Research News & Studies => Topic started by: Mishma on December 08, 2015, 11:41:50 am
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http://www.nature.com/articles/srep17808
A Novel Class of HIV-1 Antiviral Agents Targeting HIV via a SUMOylation-Dependent Mechanism
Ikenna G. Madu, Shirley Li, Baozong Li, Haitang Li, Tammy Chang, Yi-Jia Li, Ramir Vega, John Rossi, Jiing-Kuan Yee, John Zaia & Yuan Chen
We have recently identified a chemotype of small ubiquitin-like modifier (SUMO)-specific protease (SENP) inhibitors. Prior to the discovery of their SENP inhibitory activity, these compounds were found to inhibit HIV replication, but with an unknown mechanism. In this study, we investigated the mechanism of how these compounds inhibit HIV-1. We found that they do not affect HIV-1 viral production, but significantly inhibited the infectivity of the virus. Interestingly, virions produced from cells treated with these compounds could gain entry and carry out reverse transcription, but could not efficiently integrate into the host genome. This phenotype is different from the virus produced from cells treated with the class of anti-HIV-1 agents that inhibit HIV protease. Upon removal of the SUMO modification sites in the HIV-1 integrase, the compound no longer alters viral infectivity, indicating that the effect is related to SUMOylation of the HIV integrase. This study identifies a novel mechanism for inhibiting HIV-1 integration and a new class of small molecules that inhibits HIV-1 via such mechanism that may contribute a new strategy for cure of HIV-1 by inhibiting the production of infectious virions upon activation from latency.
Another potential ally in our fight for treatment and a cure. Given that many HIV +
s under treatment are non-compliant due to drug toxicities and or side effects, we desperately need new drugs that are better tolerated. This is one such drug.
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Wow - sounds like a potential break through !!! Going to be interesting to Follow!
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Very interesting, thanks for sharing :)