FightAIDS@Home – Phase 1 researchers identified new potential targets for antivirals
https://www.worldcommunit...sArticle.do?articleId=629Als ik het goed begrijp is er een 'gat' ontdekt in het virale RNA dat opgevuld kan worden waardoor het virus dan niet meer kan repliceren. Vervolgens is er met FightAIDS@Home – Phase 1 gezocht naar mogelijke kandidaten om dat gat te vullen en dat is dus blijkbaar gelukt.By: The FightAIDS@Home research team
1 Jul 2020
Summary
A protein called HIV-1 capsid (CA), which is crucial to the replication of HIV, may have some recently discovered vulnerabilities.

Given these observations, we performed a preliminary high-throughput virtual
screen focusing on the NDI pocket using the FightAIDS@Home project (FA@H; http://
fightaidsathome.scripps.edu/Capsid/index.html) in collaboration with IBM’s World
Community Grid (https://www.worldcommunitygrid.org/). More than 1.6 million com-
mercially available compounds have been used to target, inter alia, 20 conformations
of the NDI pocket, selected from hexameric and pentameric interface assemblies.
Preliminary results show that the NDI pocket is a plausible binding site for antiviral
compounds (Fig. 9) from a molecular docking point of view. Evaluation and character-
ization of these compounds are the subjects of an ongoing independent study.
Fig. 9
In conclusion, through biochemical, virological, TEM, crystallographic, and MD
simulation analyses, we characterized interactions primarily present in pentameric
interfaces in the HIV-1 capsid core and showed them to be important for assembly. Our
data highlighted the importance of a novel N-terminal domain interface (NDI) pocket
that is amenable to antiviral targeting.