Cadima Couto, Carla IrisTauzin, AlexandraFreire, João MiguelFigueira, Tiago N.Silva, Rúben D. M.Pérez-Peinado, ClaraCunha-Santos, CatarinaBártolo, InêsTaveira, NunoGano, LurdesCorreia, João D. G.Goncalves, JoaoMammano, FabrizioAndreu, DavidCastanho, Miguel A. R. B.Veiga, Ana Salomé2021-04-062021-04-062020ACS Infect Dis. 2021 Jan 8;7(1):6-22http://hdl.handle.net/10451/47245Copyright © 2020 American Chemical SocietyThere is an urgent need for the development of new anti-HIV 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.engCXCR4HIVAntagonistAntiviral drugsPeptidejournal article10.1021/acsinfecdis.9b005072373-8227