Antiviral activity of peptide inhibitors derived from the protein E stem against Japanese encephalitis and Zika viruses

Abstract

Japanese encephalitis virus (JEV) and Zika virus (ZIKV) are mosquito-borne viruses of the Flavivirus genus that cause viral encephalitis and congenital microcephaly, respectively, in humans, and thus present a risk to global public health. The envelope glycoprotein (E protein) of flaviviruses is a class II viral fusion protein that mediates host cell entry through a series of conformational changes, including association between the stem region and domain II leading to virion-target cell membrane fusion. In this study, peptides derived from the JEV E protein stem were investigated for their ability to block JEV and ZIKV infection. Peptides from stem helix 2 inhibit JEV infection with the 50% inhibitory concentration (IC₅₀) in the nanomolar range. One of these peptides (P5) protected mice against JEV-induced lethality by decreasing viral load, while abrogating histopathological changes associated with JEV infection. We also found that P5 blocked ZIKV infection with IC₅₀ at the micromolar level. Moreover, P5 was proved to reduce the histopathological damages in brain and testes resulting from ZIKV infection in type I and II interferon receptor-deficient (AG6) mice. These findings provide a basis for the development of peptide-based drugs against JEV and ZIKV.

Keywords: Glycoprotein; Japanese encephalitis virus; Peptide inhibitors; Stem; Zika virus.