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

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.

Aminopyrimidine Derivatives as Multiflavivirus Antiviral Compounds Identified from a Consensus Virtual Screening Approach

“…In its active form, this serine protease complexes with the NS2B cofactor (NS2B-NS3) and is essential for cleaving the polyprotein and releasing other essential proteins for viral replication. Due to its essentiality and mechanistic conservation, the NS3 pro remains an interesting antiviral target , for development of panflavivirus bioactive compounds. ,− Until now, NS3 pro inhibitors have mainly focused on peptides − or peptidomimetic inhibitors. − However, they have poor in vivo bioavailability and high molecular weight. − Nonpeptide active compounds have increased bioavailability − but remain to be further developed. The combination of a diverse set of computational techniques can be useful to identify novel nonpeptide hit compounds. − Furthermore, previous computational approaches helped in the development of viral protease inhibitors, such as boceprevir and ritonavir, and recently both SARS-CoV-2 main protease (M pro ) inhibitors, nirmatrelvir and ensitrelvir …”

Novel Antiviral Agents: Synthesis, Molecular Modelling Studies and Biological Investigation

“…Overall, the findings of this work indicated that the DV2 peptide could be a promising agent for treating ZIKV infections, possibly preventing or reducing neurological impairment in neonates linked to infection in pregnant women. Moreover, this work provided indications for developing anti-flavivirus drugs from synthetic stem-based peptides [ 8 ].…”