Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 21 March 2020 / Approved: 23 March 2020 / Online: 23 March 2020 (07:40:50 CET)

How to cite: Kouhpayeh, S.; Shariati, L.; Boshtam, M.; Rahimmanesh, I.; Mirian, M.; Zeinalian, M.; Salari-jazi, A.; Khanahmad, N.; Damavandi, M.S.; Sadeghi, P.; Khanahmad, H. The Molecular Story of COVID-19; NAD+ Depletion Addresses All Questions in this Infection. Preprints 2020, 2020030346 (doi: 10.20944/preprints202003.0346.v1). Kouhpayeh, S.; Shariati, L.; Boshtam, M.; Rahimmanesh, I.; Mirian, M.; Zeinalian, M.; Salari-jazi, A.; Khanahmad, N.; Damavandi, M.S.; Sadeghi, P.; Khanahmad, H. The Molecular Story of COVID-19; NAD+ Depletion Addresses All Questions in this Infection. Preprints 2020, 2020030346 (doi: 10.20944/preprints202003.0346.v1).

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.

Subject Areas

COVID-19; nCoV 19; oxidative stress; PARP; PARG; TRPM2

Comments (1)

Comment 1
Received: 3 May 2020
The commenter has declared there is no conflict of interests.
Comment: If this abstract is anything to go by, much needs to be addressed.
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