همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

3D modeling of the spike protein in the Omicron variant of the coronavirus and comparison with the Delta and Wuhan strains

نویسندگان :

Ali Abolhasanzadeh Parizi¹

1- University of Sistan and Baluchestan

کلمات کلیدی :

SARS-CoV-2 variants،Spike protein،Omicron BA.5،Viral transmissibility

چکیده :

Introduction: The spike protein mediates SARS-CoV-2 entry into human cells, stimulates neutralizing immune responses in humans, and is the basis of current COVID-19 mRNA vaccines (Krammer, 2020, Li, 2016). As the coronavirus spreads, mutations occur in its structure, primarily affecting its spike protein, resulting in multiple variants of this virus (Kandeel et al., 2022, Wang and Cheng, 2022). Omicron is the most distinct variant observed in significant numbers during the pandemic, raising concerns that it may be associated with increased transmissibility and reinfection risk and potentially reduce the effectiveness of existing vaccines (Kumar et al., 2022). This study compares the spike proteins of Delta, Omicron BA.5, and the Wuhan-Hu-1 (wild-type) strain, focusing on their binding affinities to ACE2 and furin, using computational tools to analyze their differences. Methods: The spike protein FASTA sequences for Wuhan-Hu-1, Delta, and Omicron BA.5 strains were obtained from Uniprot, ViralZone, and NCBI databases. Protein modeling was performed using the Swiss Model server (Schwede et al., 2003) by selecting appropriate templates and building 3D models. The quality of the models was assessed using the PSVS online tool through Ramachandran plot analysis. Protein domains (S1, S2, and RBD) were identified using the Interproscan (Jones et al., 2014) plugin in the Geneious Prime 2021.1.1 (https://www.geneious.com). The modeled structures were visualized using PyMOL software (Schrödinger LLC). Physicochemical parameters were analyzed using ExPASy ProtParam (Gasteiger et al., 2005). Sequence alignments were performed using Clustal Omega (Sievers and Higgins, 2014) to identify conserved amino acids and mutations. Intrinsically disordered regions (IDRs) were predicted using the IUPred3 online tool, which identifies unstructured protein regions by analyzing amino acid interaction energies (Erdős et al., 2021). Results: The analysis revealed that the Omicron BA.5 variant has accumulated 36 mutations compared to the Wuhan-Hu-1 strain and 35 mutations compared to the Delta variant. More than 40% of these mutations are concentrated in the receptor-binding domain (RBD). The Omicron BA.5 variant demonstrates potentially higher stability due to a higher aliphatic index (84.86) and an increased number of charged amino acids, potentially resulting in stronger ionic interactions. The furin cleavage site mutation (P681H) in Omicron BA.5 likely enhances protease recognition and viral entry. Moreover, the RBD of Omicron BA.5 maintains an "open" conformation, allowing it to be consistently ready for binding with the ACE2 receptor, which may contribute to its increased transmissibility. This protein variant also displays fewer disordered regions than other variants, indicating a more stable structure. Collectively, these structural changes may explain the enhanced transmissibility and immune evasion capabilities of Omicron BA.5. Conclusion: This study used bioinformatics tools to compare the spike proteins of the Omicron BA.5 variant with the Wuhan-Hu-1 and Delta strains. An analysis of the protein sequences and modeled structures revealed that the spike protein of Omicron BA.5 has undergone numerous mutations compared to earlier variants. These mutations can influence the protein's physical and chemical properties. Most of these mutations are located in the receptor-binding domain (RBD), which could enhance binding efficiency to the ACE2 receptor while potentially reducing vaccine effectiveness.