Background:
HIV-1 Gag nucleocapsid (NC) domain plays a critical role in viral RNA packaging and host cell translation modulation via interactions with proteins like Staufen-1 and eEF2. These interactions suppress stress granules, facilitating the formation of SHRNP complexes crucial for viral assembly. Disrupting these NC-host interactions could inhibit HIV-1 assembly and release, reducing viral replication.
Objectives:
1. Identify NC binding sites essential for viral assembly.
2. Screen small molecules with SeeSAR to target NC-host interactions.
3. Optimize promising compounds through structure-activity relationship (SAR) analysis.
Methods: Structural data will identify NC interaction sites, followed by SeeSAR in silico screening. Lead compounds will be optimized using SAR and tested in vitro for effects on NC interactions, SHRNP formation, and viral assembly.
Outcome: Discovery of compounds that inhibit HIV-1 assembly, advancing novel antiviral therapy
Blessed intends to achieve the following milestones:
- Identify binding sites and initiate docking with SeeSAR.
- SAR refinement of lead compounds.
- Report findings and prepare for publication/patent.