Introduction
Covid-19 (Coronavirus disease of 2019 ) is
caused by severe acute respiratory syndrome Coronavirus (SARS-CoV-2)
infection, which causes acute respiratory distress and lung fibrosis and
has resulted in more than ~10 million reported cases and
more than ~500,000 deaths worldwide as of 28th June 2020
(https://coronavirus.jhu.edu/map.html). The extent of the severity
of disease is still to be assessed with reasons for mortality linked
with Covid-19, being an evolving process with plethora of pathological
conditions being reported in an acute period. Epidemiological and cross
disciplinary aspect of the virus has been studied (Sun et al., 2020). A
retrospective study reported from Wuhan reported that 100% of the
patients suffered from acute respiratory distress syndrome and sepsis,
more than 50% patients with type I respiratory failure, acute cardiac
injury and heart failure, with some cases of kidney injury and hypoxic
encephalopathy (Chen et al., 2020). The disease is fatal with seniors
and people with comorbidities such as diabetes, obesity (Petrakis et
al., 2020), asthma, cardiovascular risks (Cheng et al., 2020) etc.
Moreover more recent reports suggest that the disease is not sparing
people of younger age groups, with symptoms of acute inflammation and
thrombosis leading to large vessel ischemic strokes becoming another
reason for mortality in Covid-19 patients (Oxley et al., 2020). Vaccines
and new drugs are being developed targeting various mechanisms through
which SARS-CoV-2 may be affecting different biological pathways and
organ failures, with an absolute cure still elusive.
To effectively target SARS-CoV-2, understanding the mechanisms of the
CoV-family may be important. Before the Covid-19, similar zoonotic
outbreaks occurred with the SARS-CoV outbreak in 2002 (Drosten et al.,
2003) and the MERS-CoV outbreak in 2012 . Prior to that human
coronaviruses, HCoV-229E and HCoV-OC43, have existed and caused common
cold (Malik, 2020). Interestingly SARS-CoV2 is not a direct descendent
of SARS-CoV however both belong to order Nidovirales . This
uniqueness in the SARS-CoV-2 or Covid-19 could explain why it may be so
much more deadly than the viruses from the same genome order. Due to
these similarities and uniqueness, often targeting the virus itself may
become complicated. However, with more reports of pathological mode of
action on cells and organs, various treatments are directed towards the
pathogenesis of Covid-19.
Pathogenesis of Covid-19 mainly includes release of pro-inflammatory
proteins also referred as a “cytokine storm”, oxidative stress, cell
death, activation of renin-angiotensin pathway and endothelial
dysfunction which ultimately lead to lung injury. Identification of any
drug or inhibitor beneficial in treating these pathogenesis, pulmonary
symptoms or thrombosis would prove to be lifesaving at this time for
Covid-19.
Poly (ADP-ribose) polymerase 1 (PARP1) is a polymerase enzyme with
multifunctional role to play in a cell (Hassa, 2009; Rajawat et al.,
2017a; Rajawat et al., 2017b), primarily maintaining genomic integrity
and cell survival being the distinct feature. PARP1 regulates several
genes either directly as transcription factors or as coactivator or
inhibitor. Additionally, PARP1 has been reported to be involved in
cytokine regulation, inflammation, pulmonary diseases and strokes.
Therefore, PARP1 inhibition has emerged as a powerful tool to control
inflammation in several organ injuries and diseases. PARP inhibitors are
such compounds which are significantly beneficial in preventing or
inhibiting inflammation, pulmonary disease symptoms, cardiovascular
disease and stroke. Several PARP inhibitors are in clinical trial for
cancer, neurodegenerative diseases and stroke. Some have been approved
by FDA already; therefore, use of PARP inhibitors would be safe too.
PARP1 has been shown to play a key role in the pathogenesis of several
viral diseases (Grady et al., 2012; Hassumi-Fukasawa et al., 2012;
Lupey-Green et al., 2018; Na et al., 2016; Xia et al., 2020). Moreover,
PARP1 and other members of PARP family are known to exhibit either
antiviral or pro-viral activities against various viruses.
In this review we have discussed the role PARP plays in regulating viral
infection or virulence, pulmonary diseases, inflammatory diseases,
cardiovascular diseases and in regulating cytokine storm. We also
explore the role of PARP1 which may result in symptoms that has been
observed in Covid-19 patients and hence the potential of PARP inhibitors
to be used for reducing the SARS-CoV-2 mediated pathogenesis.