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Dual-Action Inhibitor For Fighting HIV

ACS Meeting News: Chemists create compounds capable of binding both coreceptors HIV uses to infect T cells

by Bethany Halford
March 30, 2015 | A version of this story appeared in Volume 93, Issue 13

This week’s selections are from the ACS national meeting, which took place on March 22–26 in Denver.

HIV hijacks healthy T cells by fusing with them and making them replicate the deadly virus. The complex process requires a protein on the virus’s outer covering to bind with a receptor and coreceptor on the T cell. In some T cells, the coreceptor is CCR5, and in others, it’s CXCR4. No single drug available today blocks both of these coreceptors, so Dennis C. Liotta and colleagues at Emory University wondered whether they could come up with one. They overlaid the structures of CCR5 and CXCR4 and found a structurally similar binding motif in both coreceptors. They then virtually screened small molecules and found some that should block both coreceptors. Anthony Prosser, a graduate student in Liotta’s lab, devised a synthesis of one such compound and made many analogs (example shown). The molecules not only inhibited HIV’s binding to both CCR5 and CXCR4, but they also blocked HIV reverse transcriptase, an enzyme that’s key to the virus’s ability to copy itself. Liotta noted that the compounds are still in early development, but if successful, they could lead to a low-cost HIV treatment.


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