Repositioning PARP inhibitors for SARS-CoV-2 infection (COVID-19); a new multi-pronged therapy for ARDS?

Nicola Curtin, Krisztián Bányai, James Thaventhiran, John Le Quesne, Zsuzsanna Helyes, Péter Bai

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

Clinically approved PARP inhibitors (PARPi) have a mild adverse effect profile and are well-tolerated as continuous daily oral therapy. We review the evidence that justifies the repurposing of PARPi to block the proliferation of SARS-CoV-2 and combat the life-threatening sequelae of COVID-19 by several mechanisms. PARPi’s can effectively decrease IL-6, IL-1 and TNFα levels (key interleukins in SARS-CoV-2-induced cytokine storm) and can alleviate subsequent lung fibrosis, as demonstrated in murine experiments and clinical trials. PARPi can tune macrophages towards a tolerogenic phenotype. PARPi’s may also counteract SARS-CoV-2-induced and inflammation-induced cell death and support cell survival. PARPi’s had beneficial effects in animal models of acute respiratory distress syndrome (ARDS), asthma and ventilator-induced lung injury. PARPi’s may potentiate the effectiveness of Tocilizumab, Anakinra, Sarilumab, Adalimumab, Canakinumab or Siltuximab therapy. In summary, the evidence suggests that PARPi therapy would benefit COVID-19 patients and trials of these drugs should be undertaken.

Original languageEnglish
JournalBritish journal of pharmacology
DOIs
Publication statusAccepted/In press - 2020

Keywords

  • ARDS
  • ARTD
  • Adalimumab
  • Anakinra
  • COVID-19
  • IL6
  • NAD+
  • PARP
  • PARP inhibitor
  • SARS-COV-2
  • Sarilumab
  • Siltuximab
  • Tocilizumab
  • apoptosis
  • chloroquine
  • cytokine release syndrome
  • hydroxychloroquine
  • lopinavir
  • lung fibrosis
  • macrodomain
  • macrophage overactivation syndrome
  • mechanical ventilation
  • nicotinamide-riboside
  • olaparib
  • remedsivir
  • ritonavir
  • rucaparib
  • talazoparib

ASJC Scopus subject areas

  • Pharmacology

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