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

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.

GENETIC UNIFORMITY OF A SPECIFIC REGION UN SARS-CoV-2 GENOME AND REPURPOSING OF N-ACETYL-D- GLUCOSAMINE

The causative agent of the viral pneumonia outbreak in the world identified as SARS-CoV-2 leads to a severe respiratory illness like SARS and MERS. The pathogen spreading has turned into a pandemic dissemination and increased the mortality rate. Therefore, any useful information is essential for effective control of the disease. Our findings show the existence of unvarying sequence with no mutation in ORF lab regions from 134 high-quality filtered genome sequences of SARS-CoV-2 downloaded from the GISAID database. We have detected this sequence region by using MAUVE analysis and pair-wise alignment using Global Needleman Wunsch algorithm. All these results were also confirmed with the Clustal W analysis. The first 6500 bp of the consensus genome including ORFlab region is an unvarying sequence in SARS-CoV-2 genome. Unvarying sequence in SARS-CoV-2 genome has been very similar to another spike protein, which belongs to feline infectious peritonitis virus strain UU4 (PDB 6JX7), depending on amino acid sequences encoded, and N-acetyl-D-glucosamine is the ligand of this protein according to the highest TM-score of predicted protein structure analysis. These results have confirmed that N-acetyl-D-glucosamine could play an important effect on pathogenicity of SARS-CoV-2. Also, our molecular docking analysis data supports a strong protein-ligand interaction of N-acetyl-D-glucosamine with spike receptor-binding domain bound with ACE2 (PDB 6M0J) and RNA-binding domain of nucleocapsid phosphoprotein (PDB 6WKP) from SARS-CoV-2. Therefore, binding of N-acetyl-D-glucosamine to these proteins could inhibit SARS-CoV-2's replication. In the present work, we have suggested providing a repurposing compound for further in vitro and in vivo studies and new insights for ongoing clinical treatments as a new strategy to control of SARS-CoV-2 infections.