Molecular dynamics analysis of N-acetyl-D-glucosamine against specific SARS-CoV-2’s pathogenicity factors

Abstract

The causative agent of the pandemic identified as SARS-CoV-2 leads to a severe respiratory illness similar to SARS and MERS with fever, cough, and shortness of breath symptoms and severe cases that can often be fatal. In our study, we report our findings based on molecular docking analysis which could be the new effective way for controlling the SARS-CoV-2 virus and additionally, another manipulative possibilities involving the mimicking of immune system as occurred during the bacterial cell recognition system. For this purpose, we performed molecular docking using computational biology techniques on several SARS-CoV-2 proteins that are responsible for its pathogenicity against N-acetyl-D-glucosamine. A similar molecular dynamics analysis has been carried out on both SARS-CoV-2 and anti-Staphylococcus aureus neutralizing antibodies to establish the potential of N-acetyl-D-glucosamine which likely induces the immune response against the virus. The results of molecular dynamic analysis have confirmed that SARS-CoV-2 spike receptor-binding domain (PDB: 6M0J), RNA-binding domain of nucleocapsid phosphoprotein (PDB: 6WKP), refusion SARS-CoV-2 S ectodomain trimer (PDB: 6X79), and main protease 3clpro at room temperature (PDB: 7JVZ) could bind with N-acetyl-D-glucosamine that these proteins play an important role in SARS-CoV-2’s infection and evade the immune system. Moreover, our molecular docking analysis has supported a strong protein-ligand interaction of N-acetyl-D-glucosamine with these selected proteins. Furthermore, computational analysis against the D614G mutant of the virus has shown that N-acetyl-D-glucosamine affinity and its binding potential were not affected by the mutations occurring in the virus’ receptor binding domain. The analysis on the affinity of N-acetyl-D-glucosamine towards human antibodies has shown that it could potentially bind to both SARS-CoV-2 proteins and antibodies based on our predictive modelling work. Our results confirmed that N-acetyl-D-glucosamine holds the potential to inhibit several SARS-CoV-2 proteins as well as induce an immune response against the virus in the host.

Blood-brain barrier penetration of non-replicating SARS-CoV-2 and S1 variants of concern induce neuroinflammation which is accentuated in a mouse model of Alzheimer’s disease

“…The sugars most often associated with glycoprotein uptake of viruses are sialic acid, N-acetylglucosamine, N-acetylgalactosamine, mannose, and fucose ( Shilatifard et al, 1993 , Ushijima et al, 1992 ), with evidence that sialic acid and N-acetylglucosamine are involved in S1 binding and SARS-CoV-2 uptake ( Baysal et al, 2021 , Nguyen et al, 2022 ). Here we used lectins selective for these sugars (WGA: sialic acid and N-acetyl-D-glucosamine, LEL: N-acetylglucosamine and N-acetylgalactosamine, LTL: fucose arabinose, RCA: N-acetylgalactosamine and N-acetylglucosamine, GNL: mannose, SNA: sialic acid) to determine which were most likely to be involved in I-S1 transport across the BBB and uptake by peripheral tissues ( Table 1 ).…”

Associations of habitual glucosamine use with SARS‐CoV‐2 infection and hospital admission and death with COVID‐19: Evidence from a large population based cohort study

“…By contrast, the initial infection of SARS‐CoV‐2 can trigger, but might not directly involve massive inflammatory responses, and therefore glucosamine use does not alter the susceptibility to COVID‐19 positivity. In addition, previous research confirmed that N‐acetyl‐ d ‐glucosamine, the acetylated derivative of glucosamine, held the potential to suppress several SARS‐CoV‐2 proteins, and induced an immune response against the virus in the host 40 . Moreover, glucosamine has been shown to promote the formation of other structures within various extracellular matrices (ECMs) 41 .…”

Comparative metabolic profiling of mycelia, fermentation broth, spore powder and fruiting bodies of Ophiocordyceps gracilis by LC–MS/MS

“…l ‐Gulose is a particularly important rare sugar, as it is the sugar moiety to serve as a key building block for the preparation of the broad‐spectrum anticancer drug bleomycin and l ‐nucleoside‐based antiviral agents 36 . In addition, N ‐acetyl‐ d ‐galactosamine from Agaricus bisporus possesses anti‐tumour and immunomodulating activities, and N ‐acetyl‐ d ‐glucosamine can inhibit several SARS‐CoV‐2 proteins and induce an immune response against the virus in the host 37,38 . Amino acids serve as the basic component unit of proteins and participate in the composition of enzymes, hormones, and vitamins, playing a crucial role in regulating physiological function and catalysing metabolism 39,40 .…”