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

Curtin, Nicola; Bányai, Krisztián; Thaventhiran, James; Le Quesne, John; Helyes, Zsuzsanna; Bai, Péter

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.