Relevance of the Bruton Tyrosine Kinase as a Target for COVID-19 Therapy

Mol Cancer Res. 2021 Apr;19(4):549-554. doi: 10.1158/1541-7786.MCR-20-0814. Epub 2020 Dec 16.

Abstract

The outbreak of the novel coronavirus disease 2019 (COVID-19) has emerged as one of the biggest global health threats worldwide. As of October 2020, more than 44 million confirmed cases and more than 1,160,000 deaths have been reported globally, and the toll is likely to be much higher before the pandemic is over. There are currently little therapeutic options available and new potential targets are intensively investigated. Recently, Bruton tyrosine kinase (BTK) has emerged as an interesting candidate. Elevated levels of BTK activity have been reported in blood monocytes from patients with severe COVID-19, compared with those from healthy volunteers. Importantly, various studies confirmed empirically that administration of BTK inhibitors (acalabrutinib and ibrutinib) decreased the duration of mechanical ventilation and mortality rate for hospitalized patients with severe COVID-19. Herein, we review the current information regarding the role of BTK in severe acute respiratory syndrome coronavirus 2 infections and the suitability of its inhibitors as drugs to treat COVID-19. The use of BTK inhibitors in the management of COVID-19 shows promise in reducing the severity of the immune response to the infection and thus mortality. However, BTK inhibition may be contributing in other ways to inhibit the effects of the virus and this will need to be carefully studied.

Publication types

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

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Agammaglobulinaemia Tyrosine Kinase / antagonists & inhibitors*
  • Agammaglobulinaemia Tyrosine Kinase / metabolism
  • Antiviral Agents / adverse effects
  • Antiviral Agents / pharmacology*
  • Benzamides / pharmacology
  • COVID-19 / complications
  • COVID-19 / enzymology
  • COVID-19 Drug Treatment*
  • Humans
  • Lung / drug effects
  • Lung / virology
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy
  • Neoplasms / virology
  • Piperidines / pharmacology
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / pharmacology
  • Pyrazines / pharmacology
  • Thrombosis / drug therapy
  • Thrombosis / virology

Substances

  • Antiviral Agents
  • Benzamides
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrazines
  • ibrutinib
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human
  • acalabrutinib
  • Adenine