Figure 2. String analysis of PARP1 interaction with cytokines.
Multiple FDA approved PARP inhibitors are in clinical trials for cancer and other pathologies. Protective effects of PARP inhibitors have been demonstrated in in vivo models of non-oncological diseases. Recently in silico and in vitro analysis indicated that PARP inhibitor, a cancer drug Mefuparib (CVL218) exhibits antiviral activity against SAR-CoV-2. CVL218 was also shown to suppress the IL-6 production in PBMCs proposing its beneficial effect in SARS-CoV-2 induced immunopathology. The antiviral activity of CVL218 was more potent as compared to Remdesivir (Ge et al., 2020). Curtin and colleagues have also suggested the importance of repositioning of PARP inhibitors as a multi-pronged therapy for Covid-19 (Curtin et al., 2020). Based on these reports another PARP inhibitor, 2X-121 (former name E7449) has entered in preclinical study to assess its efficacy in Covid-19. 2X-121 is currently under Phase 2 for treatment of advanced ovarian cancer and metastatic breast cancer (https://clinicaltrials.gov/ct2/show/NCT03562832). These approaches have opened a new paradigm of inhibitors to be used against SARS-CoV-2 infection either directly or after repurposing. To explore a potential therapeutic for Covid-19, PARP inhibitors appear to be a promising approach.
Graphical Abstract