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

This article is protected by copyright. All rights reserved.

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

Year of Publication: 2020
Contained in: British journal of pharmacology (22.05.2020)
All journal articles: Search for all articles in this journal
Language: English
Contributors: Curtin, Nicola | Author
Bányai, Krisztián
Thaventhiran, James
Le Quesne, John
Helyes, Zsuzsanna
Bai, Péter
Full text access:
Electronic availability is being checked...
Links: Full Text (dx.doi.org)
Keywords: ARDS
ARTD
Adalimumab
Anakinra
COVID-19
IL6
Journal Article
NAD+
PARP inhibitor
PARP
Review
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
ISSN: 1476-5381
Note: Copyright: From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Notes: Date Revised 22.05.2020
published: Print-Electronic
Citation Status Publisher
Copyright: From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Physical Description: Online-Ressource
ID (e.g. DOI, URN): 10.1111/bph.15137
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