The Anti-Dengue Virus Peptide DV2 Inhibits Zika Virus Both In Vitro and In Vivo

Maria Fernanda de Castro-Amarante; Samuel Santos Pereira; Lennon Ramos Pereira; Lucas Souza Santos; Alexia Adrianne Venceslau-Carvalho; Eduardo Gimenes Martins; Andrea Balan; Luís Carlos de Souza Ferreira

doi:10.3390/v15040839

The Anti-Dengue Virus Peptide DV2 Inhibits Zika Virus Both In Vitro and In Vivo

Viruses. 2023 Mar 25;15(4):839. doi: 10.3390/v15040839.

Authors

Maria Fernanda de Castro-Amarante^{1

2}, Samuel Santos Pereira¹, Lennon Ramos Pereira¹, Lucas Souza Santos³, Alexia Adrianne Venceslau-Carvalho^{1

2}, Eduardo Gimenes Martins¹, Andrea Balan³, Luís Carlos de Souza Ferreira^{1

2}

Affiliations

¹ Laboratory of Vaccine Development, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil.
² Scientific Platform Pasteur USP, São Paulo 05508-020, Brazil.
³ Applied Structural Biology Laboratory, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil.

Abstract

The C-terminal portion of the E protein, known as stem, is conserved among flaviviruses and is an important target to peptide-based antiviral strategies. Since the dengue (DENV) and Zika (ZIKV) viruses share sequences in the stem region, in this study we evaluated the cross-inhibition of ZIKV by the stem-based DV2 peptide (419-447), which was previously described to inhibit all DENV serotypes. Thus, the anti-ZIKV effects induced by treatments with the DV2 peptide were tested in both in vitro and in vivo conditions. Molecular modeling approaches have demonstrated that the DV2 peptide interacts with amino acid residues exposed on the surface of pre- and postfusion forms of the ZIKA envelope (E) protein. The peptide did not have any significant cytotoxic effects on eukaryotic cells but efficiently inhibited ZIKV infectivity in cultivated Vero cells. In addition, the DV2 peptide reduced morbidity and mortality in mice subjected to lethal challenges with a ZIKV strain isolated in Brazil. Taken together, the present results support the therapeutic potential of the DV2 peptide against ZIKV infections and open perspectives for the development and clinical testing of anti-flavivirus treatments based on synthetic stem-based peptides.

Keywords: DV2 peptide; Zika virus; antiviral; dengue virus; flavivirus; peptide.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Chlorocebus aethiops
Cross Reactions
Flavivirus*
Mice
Peptides / pharmacology
Vero Cells
Zika Virus Infection* / drug therapy
Zika Virus*

Substances

Peptides

Grants and funding

This study was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), grant number 2016/20045-7; FAPESP, grant numbers 2018/14459-9 (M.F.C.A.), 2016/05570-8 (L.R.P.), 2022/01034-5 (A.A.V.B.C.), 2018/20162-9 (A.B.); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), grant numbers 440409/2016-0 and 407592/2016-4. Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), grant numbers 116618/2016-01 and 130787/2016-01; CAPES, grant numbers 88887.600175/2021-00 (S.S.P.).