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.