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Identification and characterization of peptides capable to interfere with the infection mechanisms of Dengue and Zika viruses

Grant number: 19/18205-4
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): March 01, 2020
Effective date (End): February 28, 2021
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
Principal Investigator:Luis Carlos de Souza Ferreira
Grantee:Lennon Ramos Pereira
Supervisor abroad: Jolanda M Smit
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Local de pesquisa : University Medical Center Groningen (UMCG), Netherlands  
Associated to the scholarship:16/05570-8 - Use of Zika virus recombinant proteins for development of diagnostic methods and vaccines, BP.DR

Abstract

Synthetic peptides have been described as potent and specific antiviral agents. Inhibitory peptides with effect on flaviviruses, including the arbovirus DENV and ZIKV, have also been investigated but so far no one is available for clinical use. On this line, our research group identified a peptide (Pep. 47), derived from DENV E protein domain III (EDIII) that have in vitro inhibitory effects to DENV infection. The Pep. 47 was identified by means of immunosignature profiles of antibodies capable to neutralize the virus. This peptide is located in the lateral loop of the EDIII protein, an important region of the E protein related to DENV infectivity and rather well conserved among different flaviviruses. This finding opens possibility that peptides derived from this region could also show inhibitory effects to different Flavivirus, such as ZIKV. Nonetheless, the mechanism by which Pep 47 promote viral infectivity inhibition is still unveiled. Thus, this project aims to screen and understand the inhibitory activity and mechanisms exerted by peptides capable to inhibit the infectivity of DENV and ZIKV. To achieve these goals, we propose an internship at the University Medical Center Groningen (UMCG), supervised by Professor Jolanda M. Smit, who has experience on study of the dynamics of virus cell entry, as well as the influence of some inhibitors on the viral cycle. At the end of the work we intend to find and characterize the inhibitory mechanisms of synthetic peptides derived from the E proteins of DENV and ZIKV.