Role of Poly(ADP-ribose) Polymerase (PARP1) in Viral Infection and its Implication in SARS-CoV-2 Pathogenesis.

ABSTRACT

BACKGROUND: Activation of Poly (ADP-ribose) polymerase 1 (PARP1), a post-translational modifying enzyme, has been shown to be involved with several inflammatory and viral diseases. OBJECTIVES: The goal of this review is to highlight the mechanisms underlying PARP1 activation during viral or infectious pathogenesis and to assess potential possibilities of using PARP1 inhibitors as a therapeutic countering of SARS-CoV-2 virus. METHODS: An extensive bibliographic search was done using Pubmed, Mendeley and google scholar with key words. Pre-prints are reported with potential caveats and studies without experimental data were excluded. RESULTS: Covid-19, a global pandemic; is associated with systemic surge of inflammatory cytokines resulting in severe inflammation of the lung, heart dysfunction, ischemia, and stroke. PARP1 regulates expression of NFkB and downstream cytokine production and its inhibition is known to attenuate the expression of inflammatory cytokines. PARP1 and other PARP family members regulate viral infection, replication, and virulence. The literature clearly suggests that PARP1 plays an important role in host-pathogen interactions and pathogenesis, with pre-clinical and in vitro studies supporting the idea that PARP1 inhibition may negatively affect viability of several viruses including the replication of the SARS-CoV and SARS-CoV-2 virus. CONCLUSION: The current review discusses mechanisms of PARP1 activation during viral infection, inflammatory diseases, cytokine expression and possibility of PARP1 in regulating cytokine storm and hyper-inflammation seen with Covid-19. Additionally, in vitro studies showing the negative regulation of SARS-CoV-2 virus replication by PARP inhibitors indicates a potential therapeutic role of PARP inhibitors for Covid-19 or its variants.