Molecular docking and dynamics studies of Nicotinamide Riboside as a potential multi-target nutraceutical against SARS-CoV-2 entry, replication, and transcription: A new insight

Abstract

The highly contagious Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which is a newborn infectious member of the dangerous beta-coronaviruses (β-CoVs) following SARS and MERS‐CoVs, can be regarded as the most significant issue afflicting the whole world shortly after December 2019. Considering CoVs as RNA viruses with a single-stranded RNA genome (+ssRNA), the critical viral enzyme RNA dependent RNA polymerase (RdRp) is a promising therapeutic target for the potentially fatal infection COVID-19. Nicotinamide riboside (NR), which is a naturally occurring analogue of Niacin (vitamin B3), is expected to have therapeutic effects on COVID-19 due to its super close structural similarity to the proven RdRp inhibitors. Thus, at the first phase of the current molecular docking and dynamics simulation studies, we targeted SARS-CoV-2 RdRp. On the next phase, SARS-CoV RdRp, human Angiotensin-converting enzyme 2, Inosine-5’-monophosphate dehydrogenase, and the SARS-CoV-2 Structural Glycoproteins Spike, Nonstructural viral protein 3-Chymotrypsin-like protease, and Papain-like protease were targeted using the docking simulation to find other possible antiviral effects of NR serendipitously. In the current study, the resulted scores from molecular docking and dynamics simulations as the primary determinative factor as well as the observed reliable binding modes have demonstrated that Nicotinamide Riboside and its active metabolite NMN can target human ACE2 and IMPDH, along with the viral S pro , M pro , PL pro , and on top of all, RdRp as a potential competitive inhibitor.

Safety evaluation of β-nicotinamide mononucleotide oral administration in healthy adult men and women

“…The administration of NMN and NR to rodents, Caenorhabditis elegans (nematodes), and Drosophila melanogaster (fruit flies) has been shown to prolong lifespan and alleviate age-related physiological decline 38 – 40 . In other reports, NMN and NR have been suggested to bind to ACE2 and IMPDH, along with SARS-CoV-2 viral proteins (Spro, Mpro, PLpro, RdRp) by molecular docking and dynamics simulations, suggesting a potential therapeutic effect of NMN and NR in the treatment of COVID-19 41 .…”

Are Nutraceuticals Effective in COVID-19 and Post-COVID Prevention and Treatment?

“…The recent Omicron variant is characterized by 32 mutations in the spike glycoprotein, including 15 of them in the RBD [ 55 ]. Numerous molecular modeling docking studies on natural compounds have been carried out to evaluate their anti-ACE2 activity by the preventing RBD–ACE2 interaction [ 56 , 57 , 58 ]. Laboratory and clinical data support the possible advantages that some bacterial and molecular compounds may determine in the immune response to respiratory viruses and their regulatory role in systemic inflammation or endothelial damage, both representing two essential aspects of COVID-19 [ 59 ].…”

Advances in Pathogenesis, Progression, Potential Targets and Targeted Therapeutic Strategies in SARS-CoV-2-Induced COVID-19

“…Nicotinamide analogs, such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), are an important class of natural vitamin derivatives. A relevant study found that it can effectively inhibit ACE2, so it is considered a potential inhibitor for the treatment of COVID-19 ( 113 ). However, these are only theoretical speculations and almost no basic or clinical research verification.…”