Using In Silico Bioinformatics Algorithms for the Accurate Prediction of the Impact of Spike Protein Mutations on the Pathogenicity, Stability, and Functionality of the SARS-CoV-2 Virus and Analysis of Potential Therapeutic Targets

Abstract

Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have used bioinformatics to investigate seventeen mutations in the spike protein of SARS-CoV-2, as this mediates infection of human cells and is the target of most vaccine strategies and antibody-based therapies. Two mutations, H146Y and S221W, were identified as being most pathogenic. Mutations at positions D614G, A829T, and P1263L might also have deleterious effects on protein function. We hypothesized that candidate small molecules may be repurposed to combat viral infection. We investigated changes in binding energies of the ligands and the mutant proteins by assessing molecular docking. For an understanding of cellular function and organization, protein-protein interactions are also critical. Protein-protein docking for naïve and mutated structures of SARS-CoV-2 S protein was evaluated for their binding energy with the angiotensin-converting enzyme 2 (ACE2). These interactions might limit the binding of the SARS-CoV-2 spike protein to the ACE2 receptor or may have a deleterious effect on protein function that may limit infection. These results may have important implications for the transmission of SARS-CoV-2, its pathogenesis, and the potential for drug repurposing and immune therapies.

Interface‐Guided Computational Protein Design Reveals Bebtelovimab‐Resistance Mutations in SARS‐CoV‐2 RBD: Correlation with Global Viral Genomes and Bebtelovimab‐Escape Mutations

“…In a separate investigation, Xue et al adopted the Rosetta Flex ddG protocol to calculate the binding energies between the RBD of the S-protein and hACE2 within the complex structure. [35] Their diligent approach encompassed 48 independent ddG calculations, ultimately leading to the selection of nine mutants for experimental validation through SPR assays, guided by average ddG scores. Six of the nine mutants were found to have good agreement between the ddG and K D scores, demonstrating the accuracy.…”

The spirit of literature about the underlying problems facing patients’ health and rights caused by pharmaceutical businesses: A text mining based systematic review

“…Recently, different types of data mining have been deployed in medicine such as bioinformatics (Alizadehmohajer et al, 2022) but this paper proposes a novel method for nding latent topics in the literature review. LDA has attracted much attention to reveal latent topics in text using scholarly literature documents, which models each item as a nite combination over a speci c set of topics.…”

Molecular evolutionary model based phylogenetic and mutation analysis of SARS-CoV2 spike protein sequences from Asian countries: a phylogenomic approach

“…The mutational rates of RNA virus alter the function of protein. These can interfere with the functions of the transcribed proteins by affecting their stability and modulating interactions with other biological molecules (Alizadehmohajer et al, 2022). By altering their stability and regulating interactions with other biological molecules, these can prevent the transcribed proteins from carrying out their intended functions.…”