Anti-HIV-1 Activity of pepRF1, a Proteolysis-Resistant CXCR4 Antagonist Derived from Dengue Virus Capsid Protein

There is an urgent need for the development of new antiHIV drugs that can complement existing medicines to be used against resistant strains. Here, we report the anti-HIV-1 peptide pepRF1, a human serum-resistant peptide derived from the Dengue virus capsid protein. In vitro, pepRF1 shows a 50% inhibitory concentration of 1.5 nM with a potential therapeutic window higher than 53 000. This peptide is specific for CXCR4-tropic strains, preventing viral entry into target cells by binding to the viral coreceptor CXCR4, acting as an antagonist of this receptor. pepRF1 is more effective than T20, the only peptide-based HIV-1 entry inhibitor approved, and excels in inhibiting a HIV-1 strain resistant to T20. Potentially, pepRF1 can be used alone or in combination with other anti-HIV drugs. Furthermore, one can also envisage its use as a novel therapeutic strategy for other CXCR4-related diseases.

Automated summary

The anti-HIV-1 peptide pepRF1, derived from the Dengue virus capsid protein, shows promising inhibitory effects with a potential therapeutic window higher than 53,000. It specifically targets CXCR4-tropic strains, preventing viral entry into target cells by acting as an antagonist of the viral coreceptor CXCR4. Compared to T20, a peptide-based HIV-1 entry inhibitor, pepRF1 is more effective and can potentially be used alone or in combination with other anti-HIV drugs, as well as a novel therapeutic strategy for other CXCR4-related diseases.