Indian Journal of Animal Research
SCOPUSWeb of Science
  • Year: 2026
  • Volume: 60
  • Issue: 4

Evolutionary Conservation, Functional Motifs and Molecular Dynamics of SARS-CoV-2 NSP6

  • Author:
  • Mohammed Mostafa Salama1, Medhat Wahba Shafaa1, Mohamed El-Sayed El-Nagdy1, Manal F. El-Khadragy2, Ahmed E. Abdel Moneim3, Ashraf Albrakati4*, Khalid Ebraheem Hassan5, H.H. Osman4, Mohamed El-Sayed Hasan6
  • Total Page Count: 8
  • Page Number: 644 to 651

1Helwan University, Faculty of Science, Physics Department, Medical Biophysics Division, Cairo, Egypt.

2Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh11671, Saudi Arabia.

3Unit of Scientific Research, Applied College, Qassim University, Saudi Arabia.

4Department of Human Anatomy, College of Medicine, Taif University, 21944, Saudi Arabia.

5Department of Pathology, College of Medicine, Taif University, Saudi Arabia.

6University of Sadat City, Genetic Engineering and Biotechnology Research Institute, Bioinformatics Department, Sadat City 32897, Egypt.

*Corresponding Author: Ashraf Albrakati, Department of Human Anatomy, College of Medicine, Taif University, 21944, Saudi Arabia. Email: a.albrakati@tu.edu.sa

Abstract

SARS-CoV-2 Non-Structural Protein 6 (NSP6) is pivotal for viral replication, but a comprehensive understanding of its evolutionary stability, functional sites and dynamic behavior has been limited. Leveraging a newly established high-confidence 3D model, this study provides an integrative analysis of NSP6’s biology and biophysics.

The validated NSP6 structure was analyzed for conserved regions and evolutionary history using BioEdit and MEGA11 for phylogenetic tree construction. Functional motifs and post-translational modification (PTM) sites were predicted using PROSITE, SMART, MotifFinder and MotifScan. Structural classification was performed using CATH, SCOP and SUPERFAMILY. A 100 ns molecular dynamics (MD) simulation was conducted using GROMACS with the CHARMM27 force field to evaluate structural stability through RMSD, RMSF, Rg and SASA.

Phylogenetic analysis revealed NSP6’s close relationship to bat coronaviruses and identified a single, fully conserved domain across its entire 290-amino-acid length. Motif analysis identified the definitive Coronavirus replicase NSP6 domain and predicted critical PTM sites, including Casein Kinase II phosphorylation and N-myristoylation sites. Structural classification revealed an unexpected homology to cobalamin adenosyltransferase-like folds. The 100 ns MD simulation demonstrated outstanding model stability, with low RMSD (0.2-0.35 nm after 20 ns), a consistent radius of gyration (2.04±0.01 nm) and stable solvent-accessible surface area.

Keywords

Functional motifs, Molecular dynamics simulation, NSP6, Phylogenetic tree, Post-translational modifications, RMSD, RMSF, SARS-CoV-2