Understanding the role of Poly(ADP-ribose) polymerase (PARP1) and PARP
inhibitors in viral infection and pathogenesis
Abstract
Poly (ADP-ribose) polymerase 1 (PARP1) is a post-translational modifying
enzyme and is also known to act as transcription factor and
co-activator. PARP1 has been shown to be involved with diseases
resulting in increased inflammation and several viral diseases have also
been associated with PARP1 activation. PARP1 facilitates influenza A
virus entry in host cells by degrading interferon receptor type I. PARP1
regulates expression of NFkB and downstream cytokine production and its
inhibition is known to attenuate the expression of inflammatory
cytokines. Thus, PARP1 plays an important role in host-pathogen
interactions and pathogenesis. Moreover, pre-clinical and in vitro
studies have shown that PARP1 inhibition may affect viability of several
viruses including affecting replication of the SARS-CoV virus, a distant
relative of the SARS-CoV-2 virus, the one which caused the SARS epidemic
of 2002. Covid-19 has been declared a global pandemic; with symptoms of
the disease now not limited to respiratory distress alone. Severe
inflammation is observed in the lungs leading to a surge of cytokine
release systemically, affecting heart function, ischemia and stroke.
Inflammatory cytokines which are associated with severe comorbidities
and mortalities due to chronic diseases are being upregulated in an
acute fashion. There is no immediate treatment, and only palliative care
is being provided. The current review will discuss 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.