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.