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

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          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.

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          Author and article information

          Contributors
          baip@med.unideb.hu
          Journal
          Br J Pharmacol
          Br. J. Pharmacol
          10.1111/(ISSN)1476-5381
          BPH
          British Journal of Pharmacology
          John Wiley and Sons Inc. (Hoboken )
          0007-1188
          1476-5381
          22 May 2020
          : 10.1111/bph.15137
          Affiliations
          [ 1 ] Translational and Clinical Research Institute, Newcastle University Centre for Cancer Faculty of Medical Sciences, Newcastle University Newcastle upon Tyne NE2 4HH UK
          [ 2 ] Institute for Veterinary Medical Research, Centre for Agricultural Research Budapest 1143 Hungary
          [ 3 ] MRC Toxicology Unit, University of Cambridge Lancaster Road Leicester LE1 7HN UK
          [ 4 ] Leicester Cancer Research Centre, University of Leicester, Leicester Royal Infirmary Leicester LE2 7LX UK
          [ 5 ] Glenfield Hospital, University Hospitals Leicester NHS Trust Groby Road Leicester LE3 9QP UK
          [ 6 ] Department of Pharmacology and Pharmacotherapy, Medical School; Centre for Neuroscience & János Szentágothai Research Centre University of Pécs Pécs 7624 Hungary
          [ 7 ] Department of Medical Chemistry, Faculty of Medicine University of Debrecen 4032 Hungary
          [ 8 ] MTA‐DE Lendület Laboratory of Cellular Metabolism Debrecen 4032 Hungary
          [ 9 ] Research Center for Molecular Medicine, Faculty of Medicine University of Debrecen Debrecen 4032 Hungary
          Author notes
          [*] [* ] Correspondence

          Peter Bai, PhD, DSc University of Debrecen, Department of Medical Chemistry, 4032 Debrecen, Egyetem tér 1., Hungary.

          Email: baip@ 123456med.unideb.hu

          Author information
          https://orcid.org/0000-0002-6191-6616
          Article
          BPH15137 2020-BJP-0604-R.R1
          10.1111/bph.15137
          7280733
          32441764
          78ba0c2a-e56c-4564-af8c-e6249cf00810
          This article is protected by copyright. All rights reserved.

          This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

          History
          : 01 May 2020
          : 11 May 2020
          : 14 May 2020
          Page count
          Figures: 0, Tables: 0, Pages: 1, Words: 400
          Categories
          Review Article
          Review Articles
          Custom metadata
          2.0
          accepted-manuscript
          Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.4 mode:remove_FC converted:09.06.2020

          Pharmacology & Pharmaceutical medicine
          parp,artd,macrodomain,sars‐cov‐2,parp inhibitor,olaparib,talazoparib,rucaparib,il6,apoptosis,nad+,nicotinamide‐riboside,covid‐19,tocilizumab,chloroquine,hydroxychloroquine,anakinra,sarilumab,adalimumab,siltuximab,mechanical ventilation,ards,remedsivir,lopinavir,ritonavir,macrophage overactivation syndrome,cytokine release syndrome,lung fibrosis

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