Genetic Uniformity of a Specific Region in SARS-CoV-2 Genome and In-Silico Target-Oriented Repurposing of N-Acetyl-D-Glucosamine

Abstract

Causative agent of the viral pneumonia outbreak in the World identified as SARS-CoV2 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, useful information is urgently necessary for effective control of the disease. Our study shows the existence of unvarying sequence with no mutation, including ORF1ab regions in 134 high-quality filtered genome sequences of SARS-CoV2 downloaded from the GISAID database. We have detected this sequence stability by using MAUVE analysis and pairwise alignment with Global Needleman Wunsch algorithm for each two different sequences, reciprocally. They also confirmed all these results were also with the Clustal W analysis. The first 6500 bp including ORF1ab region is an unvarying sequence. According to the highest TM-score of predicted protein structure analysis, the results showed it is very similar to spike protein of feline infectious peritonitis virus strain UU4 (PDB 6JX7) depending on amino acid sequences encoded by this unvarying region, and N-acetyl-D-glucosamine is the ligand of this protein. These results have confirmed that N-acetyl-D-glucosamine could play an important role in controlling 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.

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

“…Our previous findings indicated that D-GlcNAc is a potential compound suggesting strong interaction with proteins involving the ORF1ab region. The data of our previous study showed a drastically unvarying sequence fragment in whole paired genome sequences that can be used as a target origin for designing an effective drug to SARS-CoV-2 [ 9 ]. Our results stressed that D-GlcNAc could be considered as a therapeutic option after testing its different concentrations which would be repositioned against SARS-CoV-2.…”

“…In our previous study, we have investigated unvarying regions with less mutations than the other parts of SARS-CoV-2 genome obtained from 134 different genome sequences of the GISAID database from distinct parts of the world. The amino acid sequence of the conserved region (ORF1ab region) was obtained, then subjected to homology modeling and introduced N-acetyl-D-glucosamine (D-GlcNAc) as a potential inhibitor for the selected proteins; spike receptor-binding domain bound with ACE2 (PDB 6M0J) and RNA-binding domain of nucleocapsid phosphoprotein (PDB 6WKP) from SARS-CoV-2 [ 9 ]. Previous studies have also indicated that the effectiveness of D-GlcNAc against influenza and as a starting material of oseltamivir, a purposed drug for SARS-Cov-2 treatment, D-GlcNAc has been transformed into azido group followed by implantation of a 3-pentoxy group of the desired chemical structure [ 10 , 11 ].…”

“…In this present study, we focused on the interaction of four different proteins playing major role in SARS-CoV-2 pathogenesis with D-GlcNAc by using molecular docking and further validating the results with molecular dynamics [ 9 ].…”

Data mining and molecular dynamics analysis to detect HIV-1 reverse transcriptase RNase H activity inhibitor

“…In previous studies, MAUVE analysis was conducted to gure out the stable region of the SARS-CoV-2 genome to discover the potential drug candidates matching proteins playing a role in its virulence [14][15][16].…”