Whole Genome Sequence Analysis and Homology Modelling of a 3C Like Peptidase and a Non-Structural Protein 3 of the SARS-CoV-2 Shows Protein Ligand Interaction with an Aza-Peptide and a Noncovalent Lead Inhibitor with Possible Antiviral Properties

Abstract

<p></p><p>The family of viruses belonging to Coronaviridae mainly consist of virulent pathogens that have a zoonotic property, Severe Acute Respiratory Syndrome (SARS-CoV) and Middle East Respiratory Syndrome (MERS-CoV) of this family have emerged before and now the SARS-CoV-2 has emerged in China. Characterization of spike glycoproteins, polyproteins and other viral proteins from viruses are important for vaccine development. Homology modelling of these proteins with known templates offers the opportunity to discover ligand binding sites and explore the possible antiviral properties of these protein ligand complexes. Any information emerging from these protein models can be used for vaccine development. In this study we did a complete bioinformatic analysis, sequence alignment, comparison of multiple sequences and homology modelling of the <a>SARS-CoV-2 </a>whole genome sequences, the spike protein and the polyproteins for homology with known proteins, we also analysed receptor binding sites in these models for possible binding with ligands that exhibit antiviral properties. Our results showed that the tertiary structure of the polyprotein isolate SARS-CoV-2_HKU-SZ-001_2020 had 98.94 percent identity with SARS-Coronavirus NSP12 bound to NSP7 and NSP8 co-factors. <a>Our results indicate that a part of the viral genome </a><a>(residues 3268 -3573 in Frame 2 with 306 amino acids) of the SARS-CoV-2 virus isolate Wuhan-Hu-1 (Genbank Accession Number MN908947.3) </a>when modelled with template 2a5i of the PDB database had 96 percent identity with a 3C like peptidase of SARS-CoV which has ability to bind with Aza-Peptide Epoxide (APE) which is known for irreversible inhibition of SARS-CoV main peptidase. The part of the genome (residues 1568-1882 in Frame 2 with 315 amino acids) when modelled with template 3e9s of the PDB database had 82 percent identity with a papain-like protease/deubiquitinase which when complexed with ligand GRL0617 acts as inhibitor which can block SARS-CoV replication. The regions studied was conserved in more than 90 genomes of SARS-CoV-2. It is possible that these viral inhibiters can be used for vaccine development for the SARS-CoV-2.</p><p></p><p></p>

The physicochemical and phylogenetic properties of twelve spike glycoprotein models for SARS-CoV-2 from China, Iran, and Tunisia

“…on the other hand, the Tunisian sequence (QIV64962.1) shared a 29.27% identity with the Chinese and Iranian sequences. Shanker and colleagues had studied the amino acid sequences of the seven S glycoprotein units from China and reached the same conclusion [27].…”

“…The GenBank provides unrestricted access to all types of genomic and polypeptide sequences that dealt with the novel coronavirus epidemic by SARS-CoV-2 [11]. Till the preparation of this paper (April 20th, 2020), only the Chinese sequences of S glycoprotein of SARS-CoV-2 were assessed and compared through the literature [25][26][27]. The Iranian and the Tunisian sequences were not assessed after being uploaded in the GenBank.…”

Update of the current knowledge on genetics, evolution, immunopathogenesis, and transmission for coronavirus disease 19 (COVID-19)

“…The S protein amino acid identity among the Bat-CoV ranged between 75.3% and 96.7%, with LYRa3 and RaTG13 S proteins having the lowest and highest identity to SARS-CoV-2, respectively 162 . The tertiary structure of the polyprotein isolate SARS-CoV-2_HKU-SZ-001_2020 had 98.94 % identity with SARS-Coronavirus NSP12 bound to NSP7 and NSP8 co-factors 163 .…”