The Molecular Story of COVID-19; NAD⁺Depletion Addresses All Questions in this Infection

Abstract

The emerging new Coronaviridae member, nCoV 19, outbreak announced a pandemic by WHO with an increased morbidity and mortality rate worldwide. nCoV 19 known as the third highly pathogen coronavirus in the human population after the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), the nCoV 19. The renin-angiotensin (RAS) signaling pathway, oxidative stress and cell death, cytokines storm and endothelial dysfunction are four major pathways involved in the pathogenesis of nCoV 19. Acute respiratory distress syndrome (ARDS) generally develops with a massive oxidative/nitrosative stress following virus entry and RAS activation. The DNA damage subsequent to oxidative burst activates poly-ADP ribose polymerase-1 (PARP-1), viral macrodomain (NSP3) poly (ADP-ribose) glycohydrolase (PARG) and transient receptor potential channel, melastatin 2 (TRPM2) in a sequential manner ultimately leading to apoptosis and necrosis due to NAD and ATP depletion. Regarding the molecular mechanisms involved in nCoV 19 pathogenesis, angiotensin II receptor blockers and/or PARP, PARG and TRPM2 blockers could be engaged as therapeutic candidates for inhibition of RAS and quenching oxidative stress, respectively. In this review, the molecular aspects of nCoV 19 pathogenesis would be studied precisely and possible therapeutic targets would be proposed. It is recommended to evaluate the proposed drugs and supplements via registered clinical trials along with conventional guideline-based multi-drug regimen.

β-Glucan extracts from the same edible shiitake mushroom Lentinus edodes produce differential in-vitro immunomodulatory and pulmonary cytoprotective effects — Implications for coronavirus disease (COVID-19) immunotherapies

“…Reduction in oxidative stress by use of Lentinan is relevant to COVID-19 intervention. The renin-angiotensin (RAS) signaling pathway, oxidative stress and cell death, cytokines storm and endothelial dysfunction are four major pathways involved in the pathogenesis of COVID-19 (Kouhpayeh et al, 2020). Therapeutic candidates that inhibit RAS and quench oxidative stress would be relevant for COVID-19.…”

Role of poly (ADP) ribose polymerase-1 inhibition by nicotinamide as a possible additive treatment to modulate host immune response and prevention of cytokine storm in COVID-19

“…Hence, nicotinamide, which is the first PARP inhibitor, has activity against PARP-1, PARP-2 can be used as PARP inhibitor. [21] The body's niacin requirement is met not only by nicotinic acid and nicotinamide present in the diet but also by conversion from the dietary protein-containing tryptophan. The relative contribution of tryptophan is estimated as follows: 60 mg of tryptophan = 1 mg of niacin = 1 mg of niacin equivalents.…”

Repositioning PARP inhibitors for SARS‐CoV‐2 infection(COVID‐19); a new multi‐pronged therapy for acute respiratory distress syndrome?

“…Reactive species production increases in SARS‐CoV‐2 (COVID‐19) infection (Kouhpayeh et al, 2020; Sawalha, Zhao, Coit, & Lu, 2020; Wang et al, 2020; Zhang, Wu, Li, Zhao, & Wang, 2020) that makes PARP activation and PARP activation‐mediated cell death likely. Pharmacological PARP inhibition is likely to reduce cell death under these conditions as suggested by the study on another ssRNA(+) virus, the Zika virus.…”