Interactions between SARS coronavirus 2 papain-like protease and immune system: A potential drug target for the treatment of COVID-19

Scand J Immunol. 2021 Oct;94(4):e13044. doi: 10.1111/sji.13044. Epub 2021 Aug 10.

Abstract

Coronaviruses (CoVs) are a large family of respiratory viruses which can cause mild to moderate upper respiratory tract infections. Recently, new coronavirus named as Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified which is a major threat to public health. Innate immune responses play a vital role in a host's defence against viruses. Interestingly, CoVs have evolved elaborate strategies to evade the complex system of sensors and signalling molecules to suppress host immunity. SARS-CoV-2 papain-like protease (PLpro), as an important coronavirus enzyme, regulates viral spread and innate immune responses. SCoV-2 PLpro is multifunctional enzyme with deubiquitinating (DUB) and deISGylating activity. The PLpro can interact with key regulators in signalling pathways such as STING, NF-κB, cytokine production, MAPK and TGF-β and hijack those to block the immune responses. Therefore, the PLpro can be as an important target for the treatment of COVID-19. Until now, several drugs or compounds have been identified that can inhibit PLpro activity. Here we discuss about the dysregulation effects of PLpro on immune system and drugs that have potential inhibitors for SCoV-2 PLpro.

Keywords: COVID-19; DeISGylating; deubiquitinating; papain-like protease; severe acute respiratory syndrome coronavirus 2.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / administration & dosage
  • Antiviral Agents / immunology
  • COVID-19 / immunology*
  • COVID-19 / virology
  • COVID-19 Drug Treatment
  • Coronavirus Papain-Like Proteases / immunology*
  • Coronavirus Papain-Like Proteases / metabolism
  • Cytokines / immunology
  • Cytokines / metabolism
  • Humans
  • Immune System / immunology*
  • Immune System / metabolism
  • NF-kappa B / immunology
  • NF-kappa B / metabolism
  • Protein Binding / drug effects
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / metabolism
  • SARS-CoV-2 / physiology
  • Viral Proteins / immunology*
  • Viral Proteins / metabolism

Substances

  • Antiviral Agents
  • Cytokines
  • NF-kappa B
  • Viral Proteins
  • Coronavirus Papain-Like Proteases
  • papain-like protease, SARS-CoV-2