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

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 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and combat the life-threatening sequelae of coronavirus disease 2019 (COVID-19) by several mechanisms. PARPi can effectively decrease IL-6, IL-1 and TNF-α 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 may also counteract SARS-CoV-2-induced and inflammation-induced cell death and support cell survival. PARPi is effective in animal models of acute respiratory distress syndrome (ARDS), asthma and ventilator-induced lung injury. PARPi may potentiate the effectiveness of tocilizumab, anakinra, sarilumab, adalimumab, canakinumab or siltuximab therapy. The evidence suggests that PARPi would benefit COVID-19 patients and trials should be undertaken.

Original languageEnglish
Pages (from-to)3635-3645
Number of pages11
JournalBritish journal of pharmacology
Volume177
Issue number16
DOIs
Publication statusPublished - Aug 1 2020

ASJC Scopus subject areas

  • Pharmacology

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