The Inhibition of NS2B/NS3 Protease: A New Therapeutic Opportunity to Treat Dengue and Zika Virus Infection

Int J Mol Sci. 2024 Apr 16;25(8):4376. doi: 10.3390/ijms25084376.

Abstract

In the global pandemic scenario, dengue and zika viruses (DENV and ZIKV, respectively), both mosquito-borne members of the flaviviridae family, represent a serious health problem, and considering the absence of specific antiviral drugs and available vaccines, there is a dire need to identify new targets to treat these types of viral infections. Within this drug discovery process, the protease NS2B/NS3 is considered the primary target for the development of novel anti-flavivirus drugs. The NS2B/NS3 is a serine protease that has a dual function both in the viral replication process and in the elusion of the innate immunity. To date, two main classes of NS2B/NS3 of DENV and ZIKV protease inhibitors have been discovered: those that bind to the orthosteric site and those that act at the allosteric site. Therefore, this perspective article aims to discuss the main features of the use of the most potent NS2B/NS3 inhibitors and their impact at the social level.

Keywords: NS2B/NS3 serine protease; antiviral agents; dengue virus; orthosteric and allosteric inhibitors; zika virus.

Publication types

  • Review

MeSH terms

  • Animals
  • Antiviral Agents* / pharmacology
  • Antiviral Agents* / therapeutic use
  • DEAD-box RNA Helicases
  • Dengue Virus / drug effects
  • Dengue* / drug therapy
  • Dengue* / virology
  • Humans
  • Nucleoside-Triphosphatase
  • Protease Inhibitors* / chemistry
  • Protease Inhibitors* / pharmacology
  • Protease Inhibitors* / therapeutic use
  • Serine Endopeptidases / chemistry
  • Serine Endopeptidases / metabolism
  • Viral Nonstructural Proteins / antagonists & inhibitors
  • Viral Nonstructural Proteins / chemistry
  • Viral Nonstructural Proteins / metabolism
  • Viral Proteases
  • Zika Virus / drug effects
  • Zika Virus / enzymology
  • Zika Virus Infection* / drug therapy
  • Zika Virus Infection* / virology

Substances

  • Antiviral Agents
  • DEAD-box RNA Helicases
  • NS2B protein, flavivirus
  • NS3 protein, Zika virus
  • Nucleoside-Triphosphatase
  • Protease Inhibitors
  • Serine Endopeptidases
  • Viral Nonstructural Proteins
  • Viral Proteases

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