Inhibitors of the Zika virus protease NS2B-NS3

Saan Voss; Christoph Nitsche

doi:10.1016/j.bmcl.2020.126965

Inhibitors of the Zika virus protease NS2B-NS3

Bioorg Med Chem Lett. 2020 Mar 1;30(5):126965. doi: 10.1016/j.bmcl.2020.126965. Epub 2020 Jan 11.

Authors

Saan Voss¹, Christoph Nitsche²

Affiliations

¹ Research School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.
² Research School of Chemistry, Australian National University, Canberra, ACT 2601, Australia. Electronic address: christoph.nitsche@anu.edu.au.

PMID: 31980339
DOI: 10.1016/j.bmcl.2020.126965

Abstract

In recent years, the Zika virus has emerged from a neglected flavivirus to a health-threatening pathogen that causes epidemic outbreaks associated with neurological disorders and congenital malformations. In addition to vaccine development, the discovery of specific antiviral agents has been pursued intensely. The Zika virus protease NS2B-NS3 catalyses the processing of the viral precursor polyprotein as an essential step during viral replication. Since the epidemic Zika virus outbreak in the Americas, several inhibitors of this protease have been reported. Substrate-derived peptides revealed important structural information about the active site, whilst more drug-like small molecules have been discovered as allosteric inhibitors.

Keywords: Allosteric inhibitors; Antivirals; Flavivirus; Peptides; Serine protease.

Publication types

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

MeSH terms

Animals
Antiviral Agents / therapeutic use*
Drug Discovery
Drug Repositioning
Humans
Serine Endopeptidases
Serine Proteinase Inhibitors / therapeutic use*
Viral Proteins / antagonists & inhibitors*
Zika Virus / enzymology*
Zika Virus Infection / drug therapy*

Substances

Antiviral Agents
Serine Proteinase Inhibitors
Viral Proteins
NS3 protein, zika virus
Serine Endopeptidases