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

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ID: 107706
2020
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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Authors Curtin, Nicola;Bányai, Krisztián;Thaventhiran, James;Le Quesne, John;Helyes, Zsuzsanna;Bai, Péter;
Journal british journal of pharmacology
Year 2020
DOI 10.1111/bph.15137
URL
Keywords
apoptosis hydroxychloroquine mechanical ventilation adalimumab tocilizumab chloroquine nad+ ards lung fibrosis covid-19 sars-cov-2 lopinavir ritonavir anakinra artd il6 parp parp inhibitor sarilumab siltuximab cytokine release syndrome macrodomain macrophage overactivation syndrome nicotinamide-riboside olaparib remedsivir rucaparib talazoparib

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