Evolution-Informed Viroinformatics Identifies Conserved Immune Targets with Predicted Lower Mutational Vulnerability Across Betacoronaviruses.
6 affiliations
- 1Department of Zoology, College of Science, King Saud University, Riyadh 11495, Saudi Arabia.
- 2Fuli Institute of Food Science, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, China.
- 3Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72388, Saudi Arabia.
- 4Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
- 5Department of Biology, College of Science, University of Tabuk, Tabuk 71491, Saudi Arabia.
- 6Molecular Microbiology and Infectious Diseases Research Unit, University of Tabuk, Tabuk 71491, Saudi Arabia.
Abstract
The extensive evolutionary diversity and continuous mutational adaptation of betacoronaviruses represent a major challenge to the development of broadly protective countermeasures. This study applied an evolution-informed Viroinformatics framework to systematically identify conserved and immune targets with predicted lower mutational vulnerability across betacoronaviruses. The workflow integrated comparative sequence conservation and phylogenetic analysis with immunoinformatics-based epitope screening, HLA population coverage, mutational escape profiling, structural modeling, molecular docking, and molecular dynamics simulations. Conserved cytotoxic T-lymphocyte and helper T-lymphocyte epitopes were prioritized based on immunogenicity, antigenicity, safety, HLA binding potential, evolutionary conservation, and predicted resistance to mutational escape. Combined MHC class I and II analysis predicted a theoretical global population coverage of 99.92%, which requires experimental validation. The resulting 409-amino-acid multiepitope construct was predicted to be antigenic, non-allergenic, and physiochemically stable. Structural validation showed that 99.7% of the residues were located within favored or additionally allowed regions. Molecular docking demonstrated favorable interaction of the vaccine construct with TLR7, while a 100 ns molecular dynamics simulation supported persistence of the predicted vaccine-receptor association. Overall, these findings provide a computational framework for prioritizing evolutionarily conserved immune targets and developing pre-emptive candidate epitopes showing predicted cross-betacoronavirus conservation within the analyzed dataset. Experimental studies evaluating HLA binding, cellular and humoral immunogenicity, recombinant expression, cross-reactivity, and in vivo protection are required to validate the predicted immunological potential and determine whether the proposed construct can provide broad protection against diverse betacoronaviruses.
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BibTeX
@article{alshammari2026evolutioninformed,
title = {{Evolution-Informed Viroinformatics Identifies Conserved Immune Targets with Predicted Lower Mutational Vulnerability Across Betacoronaviruses.}},
author = {Jamilah Alshammari and Huda A Alqahtani and Rasha Alonaizan and Inam Ur Rahman and Khaled Alzhrani and Nawal Al-Hoshani and Maha Abdullah Alwaili and Tariq Aziz},
journal = {Viruses},
year = {2026},
month = oct,
doi = {10.3390/v18101171},
url = {https://europepmc.org/article/MED/42944090},
note = {CC BY},
}
RIS
TY - JOUR
TI - Evolution-Informed Viroinformatics Identifies Conserved Immune Targets with Predicted Lower Mutational Vulnerability Across Betacoronaviruses.
AU - Jamilah Alshammari
AU - Huda A Alqahtani
AU - Rasha Alonaizan
AU - Inam Ur Rahman
AU - Khaled Alzhrani
AU - Nawal Al-Hoshani
AU - Maha Abdullah Alwaili
AU - Tariq Aziz
PY - 2026
DA - 2026/10/21
JO - Viruses
DO - 10.3390/v18101171
UR - https://europepmc.org/article/MED/42944090
AB - The extensive evolutionary diversity and continuous mutational adaptation of betacoronaviruses represent a major challenge to the development of broadly protective countermeasures. This study applied an evolution-informed Viroinformatics framework to systematically identify conserved and immune targets with predicted lower mutational vulnerability across betacoronaviruses. The workflow integrated comparative sequence conservation and phylogenetic analysis with immunoinformatics-based epitope screening, HLA population coverage, mutational escape profiling, structural modeling, molecular docking, and molecular dynamics simulations. Conserved cytotoxic T-lymphocyte and helper T-lymphocyte epitopes were prioritized based on immunogenicity, antigenicity, safety, HLA binding potential, evolutionary conservation, and predicted resistance to mutational escape. Combined MHC class I and II analysis predicted a theoretical global population coverage of 99.92%, which requires experimental validation. The resulting 409-amino-acid multiepitope construct was predicted to be antigenic, non-allergenic, and physiochemically stable. Structural validation showed that 99.7% of the residues were located within favored or additionally allowed regions. Molecular docking demonstrated favorable interaction of the vaccine construct with TLR7, while a 100 ns molecular dynamics simulation supported persistence of the predicted vaccine-receptor association. Overall, these findings provide a computational framework for prioritizing evolutionarily conserved immune targets and developing pre-emptive candidate epitopes showing predicted cross-betacoronavirus conservation within the analyzed dataset. Experimental studies evaluating HLA binding, cellular and humoral immunogenicity, recombinant expression, cross-reactivity, and in vivo protection are required to validate the predicted immunological potential and determine whether the proposed construct can provide broad protection against diverse betacoronaviruses.
SN - 1999-4915
ER -