Antiviral Peptides Targeting the West Nile Virus Envelope Protein

Abstract

West Nile virus (WNV) can cause fatal murine and human encephalitis. The viral envelope protein interacts with host cells. A murine brain cDNA phage display library was therefore probed with WNV envelope protein, resulting in the identification of several adherent peptides. Of these, peptide 1 prevented WNV infection in vitro with a 50% inhibition concentration of 67 M and also inhibited infection of a related flavivirus, dengue virus. Peptide 9, a derivative of peptide 1, was a particularly potent inhibitor of WNV in vitro, with a 50% inhibition concentration of 2.6 M. Moreover, mice challenged with WNV that had been incubated with peptide 9 had reduced viremia and fatality compared with control animals. Peptide 9 penetrated the murine blood-brain barrier and was found in the brain parenchyma, implying that it may have antiviral activity in the central nervous system. These short peptides serve as the basis for developing new therapeutics for West Nile encephalitis and, potentially, other flaviviruses.

West Nile Virus: Biology, Transmission, and Human Infection

“…Investigations to identify individual susceptibility markers, recombinant antibodies, peptides, RNA interference, and small molecules with the ability to directly or indirectly neutralize WNV have been reported; however, an effective drug is still lacking (6,12,70,71,74,146,158). There are currently four USDA-licensed vaccines available for equines (two are inactivated whole WNV, one is a nonreplicating live canary pox recombinant vector vaccine, and one is an inactivated flavivirus chimeric vaccine).…”

Glycoprotein E of the Japanese encephalitis virus forms virus-like particles and induces syncytia when expressed by a baculovirus

“…As there is no effective clinical therapeutic intervention in flaviviral infection, the identification of novel inhibitors to target the virus life cycle is urgently required (Geiss et al, 2009;Shi, 2002). The E protein of flaviviruses mediates interactions between the virus and host cells during the initial stages of infection; hence it is widely targeted for the development of antiviral molecules, including inhibitory peptides (Bai et al, 2007;Costin et al, 2010;Hrobowski et al, 2005), therapeutic antibodies (Thompson et al, 2009) and small molecules (Kampmann et al, 2009;Schmidt et al, 2012). Here, we have established a new approach for antiviral screening targeted to JEV E, and in particular to its role in the attachment and fusion processes.…”

Peptide P3 Selected from Phage Display Screen Shows Antiviral Activity against Porcine Reproductive and Respiratory Syndrome Virus

“…Among these, proteins from ORF1b perform as the RNAdependent RNA polymerase (NSP9), helicase (NSP10) and the conserved C-terminal domain (CTD) (NSP11) [10], which are important factors in the process of PRRSV infection [11]. Given the facts above, ORF1b can be treated as a potential target for antiviral drug screening [12][13][14][15][16].…”

“…Phage technology is an effective method for developing new drugs, and it has been applied in drug development trials increasingly [12,17,18]. Several successful cases of PRRSV inhibitors through phage screening technology were reported.…”