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

Curtin, N., Bányai, K., Thaventhiran, J., Le Quesne, J., Helyes, Z. and Bai, P. (2020) Repositioning PARP inhibitors for SARS‐CoV‐2 infection(COVID‐19); a new multi‐pronged therapy for acute respiratory distress syndrome? British Journal of Pharmacology, 177(16), pp. 3635-3645. (doi: 10.1111/bph.15137) (PMID:32441764) (PMCID:PMC7280733)

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.

• Item Type: Articles
• Additional Information: Our work was supported by grants from the Hungarian Scientific Research Fund NKFIH (K123975, GINOP-2.3.2-15-2016-0000, EFOP-3.6.2-16-2017-00008, GINOP-2.3.2 STAY ALIVE, and 20765-3/2018/FEKUTSTRAT) and by the Faculty of Medicine at the University of Debrecen. The research was financed by the Higher Education Institutional Excellence Program (NKFIH-1150-6/2019) of the Ministry of Innovation and Technology in Hungary, within the framework of the Biotechnology thematic programme of the University of Debrecen.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Le Quesne, Professor John
• Authors: Curtin, N., Bányai, K., Thaventhiran, J., Le Quesne, J., Helyes, Z., and Bai, P.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: British Journal of Pharmacology
• Publisher: John Wiley & Sons Ltd on behalf of British Pharmacological Society
• ISSN: 0007-1188
• ISSN (Online): 1476-5381
• Published Online: 22 May 2020
• Copyright Holders: Copyright © 2020 The Authors
• First Published: First published in British Journal of Pharmacology 117(16):3635-3645
• Publisher Policy: Reproduced under a Creative Commons licence