New anti-HIV drug targets identified?
Commonly used drugs normally act by targeting two viral enzymes: reverse transcriptase, responsible for creating double-stranded DNA from single-stranded RNA, and protease, the enzyme needed to digest protein. A drawback is that in the short term some 20 % of patients are adversely affected by antiviral cocktails, while long-term treatments often bring on severe side effects. Also, there is mounting concern about the emergence of drug-resistant HIV variants. The 'Identifying novel classes of anti-HIV inhibitors' (Newhivtargets) project set out to identify lead compounds with the potential to act on HIV through novel processes. The project teamed up virology and cellular biology experts with antiviral research specialists and pharmacologists to conduct anti-HIV high-throughput screening (HTS) assays. Newhivtargets members originally set out to design two assays that would not require the use of an infectious virus and would allow screening of libraries of chemicals. One was a cell-free, protein/protein interaction assay and the other was a one-cell–based assay. The team designed the one-cell–based assay, identifying one interesting hit out of 2 000 compounds. Project partners defined an unexploited viral target, chosen on the strength of recent discoveries highlighting the molecular processes of virus budding. Since there are no available inhibitors for this target, this process brings about viral release from the cell — a critical step in the HIV cycle — and makes it a possible target for drug development. Newhivtargets partners hope further screening will identify hits or lead compounds that in subsequent research could be enhanced with a classical drug design approach.