Comparative analysis of ACE2 and antibody binding affinities of post-pandemic SARS-CoV-2 variants
Abstract
Post-pandemic evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, is characterized by the continuous emergence of variants carrying numerous mutations within the receptor-binding domain (RBD) of the spike protein. These mutations may alter viral affinity for the angiotensin-converting enzyme 2 (ACE2) receptor and neutralizing antibodies, thereby influencing transmissibility and immune evasion. The aim of this study was to pe r form a comparative in silico analysis of the binding affinities of major post-pandemic SARS-CoV-2 variants toward the human ACE2 receptor and a reference neutralizing antibody. Mutational profiles of XBB.1.5, XBB.1.16, EG.5, BA.2.86, JN.1, KP.3.1.1, NB.1.8.1, XFG, and BA.3.2 lineages were analyzed, structural models of RBD-ACE2 and RBD-antibody complexes were generated, and binding free energies were estimated. Molecular dynamics simulations were performed for selected co m plexes containing RBDs of the XBB.1.5 and BA.3.2.2 variants, as well as the wild-type SARS-CoV-2, and structural stability, conformational dynamics, hydrogen bonding, and free energy landscapes were evaluated. All analyzed post-pandemic variants formed less stable complexes with the reference antibody than the wild-type virus, indicating a general evolutionary trend toward enhanced immune evasion. However, only a subset of variants demonstrated enhanced affinity for ACE2. Molecular dynamics simulations demonstrated that post-pandemic variants acquired distinct conformational dynamics and metastable states compared with the wild-type virus. In particular, XBB.1.5 and BA.3.2.2 formed more stable complexes with ACE2 and less stable co m plexes with the antibody than the wild-type virus. These findings suggest that post-pandemic SARS-CoV-2 evolution is driven predominantly by optimization of immune evasion while preserving effective receptor interaction. The study also demonstrates that the applied computational workflow may be useful for rapid characterization of newly emerging SARS-CoV-2 variants.References
Aboul-Fotouh, S., Mahmoud, A. N., Elnahas, E. M., Habib, M. Z., & Abdelraouf, S. M. (2023). What are the current anti-COVID-19 drugs? From traditional to smart molecular mechanisms. Virology Journal, 20(1), 241.
Abraham, M. J., Murtola, T., Schulz, R., Páll, S. Smith, J. C., Hess, B., & Lindahl, E. (2015). GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX, 1–2, 19–25.
Alhamlan, F. S., & Al-Qahtani, A. A. (2025). SARS-CoV-2 variants: Genetic insights, epidemiological tracking, and implications for vaccine strategies. International Journal of Molecular Sciences, 26(3), 1263.
Alshahrani, M., Gatlin, W., Ludwick, M., Turano, L., Foley, B., & Verkhivker, G. (2026). Mechanisms of binding and immune escape resistance for broadly neutralizing antibodies targeting distinct conserved SARS-CoV-2 spike epitopes: A hierarchical approach integrating mutational profiling and energy landscape analysis. International Journal of Molecular Sciences, 27(9), 4025.
Alves, M. C. S., da Silva, R. C. C., de Leitão-Júnior, S. S. P., & de Balbino, V. Q. (2025). Therapeutic approaches for COVID-19: a review of antiviral treatments, immunotherapies, and emerging interventions. Advances in Therapy, 42(7), 3045–3058.
Ambrosio, L., Chiara, M., Lo Presti, A., Poletti, P., Alteri, C., Cacchiarelli, D., Bouchè, V., Morgante, M., Ballabio, A., Perno, C. F., Merler, S., Pesole, G., & Stefanelli, P. (2022). SARS-CoV-2 variants: What have we learnt so far? Annali dell’Istituto Superiore Di Sanità, 58(2), 81–84.
Andre, M., Lau, L. S., Pokharel, M. D., Ramelow, J., Owens, F., Souchak, J., Akkaoui, J., Ales, E., Brown, H., Shil, R., Nazaire, V., Manevski, M., Paul, N. P., Esteban-Lopez, M., Ceyhan, Y., & El-Hage, N. (2023). From Alpha to Omicron: How different variants of concern of the SARS-Coronavirus-2 impacted the world. Biology, 12(9), 1267.
Ataya, F., Alamro, A., Alghamdi, A., & Fouad, D. (2025). SARS-CoV-2 spike mutations alter structure and energetics to modulate ACE2 binding immune evasion and viral adaptation. Scientific Reports, 15(1), 37546.
Ayenigbara I. O. (2020). COVID-19: An international public health concern. Central Asian Journal of Global Health, 9(1), e466.
Azhar, L. E., Samkari, D. A., Hassan, A. M., Alsayed, S. M., & Azhar, E. I. (2026). The emergence and characterization of SARS-CoV-2 variant XFG ("Stratus"): Comparative virological, epidemiological, and public-health perspectives. Journal of Epidemiology and Global Health, 16(1), 8.
Banerjee, S., Wang, X., Du, S., Zhu, C., Jia, Y., Wang, Y., & Cai, Q. (2022). Comprehensive role of SARS-CoV-2 spike glycoprotein in regulating host signaling pathway. Journal of Medical Virology, 94(9), 4071–4087.
Berendsen, H. J. C., van der Spoel, D., & van Drunen, R. (1995). GROMACS: A message-passing parallel molecular dynamics implementation. Computer Physics Communications, 91(1–3), 43–56.
Bertoglio, F., Fühner, V., Ruschig, M., Heine, P. A., Abassi, L., Klünemann, T., Rand, U., Meier, D., Langreder, N., Steinke, S., Ballmann, R., Schneider, K. T., Roth, K. D. R., Kuhn, P., Riese, P., Schäckermann, D., Korn, J., Koch, A., Chaudhry, M. Z., Eschke, K., … Hust, M. (2021). A SARS-CoV-2 neutralizing antibody selected from COVID-19 patients binds to the ACE2-RBD interface and is tolerant to most known RBD mutations. Cell Reports, 36(4), 109433.
Bocquet-Garçon, A. (2024). Impact of the SARS-CoV-2 spike protein on the innate immune system: A review. Cureus, 16(3), e57008.
Bondi, A. (1964). Van der Waals volumes and radii. Journal of Physical Chemistry, 68, 441–451.
Bourgonje, A. R., Abdulle, A. E., Timens, W., Hillebrands, J. L., Navis, G. J., Gordijn, S. J., Bolling, M. C., Dijkstra, G., Voors, A. A., Osterhaus, A. D., van der Voort, P. H., Mulder, D. J., & van Goor, H. (2020). Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19). The Journal of Pathology, 251(3), 228–248.
Burki T. (2023). WHO ends the COVID-19 public health emergency. The Lancet. Respiratory Medicine, 11(7), 588.
Cao, G., Xu, C., Wang, L., Chai, K., & Wu, B. (2025). Global surveillance and biological characterization of the SARS-CoV-2 NB.1.8.1 variant: An emerging VUM lineage under scrutiny. Viruses, 17(11), 1457.
Carabelli, A. M., Peacock, T. P., Thorne, L. G., Harvey, W. T., Hughes, J., COVID-19 Genomics UK Consortium, Peacock, S. J., Barclay, W. S., de Silva, T. I., Towers, G. J., & Robertson, D. L. (2023). SARS-CoV-2 variant biology: Immune escape, transmission and fitness. Nature Reviews. Microbiology, 21(3), 162–177.
Chen, C., Nadeau, S., Yared, M., Voinov, P., Xie, N., Roemer, C., & Stadler, T. (2022). CoV-Spectrum: Analysis of globally shared SARS-CoV-2 data to identify and characterize new variants. Bioinformatics, 38(6), 1735–1737.
Chung, Y. S., Lam, C. Y., Tan, P. H., Tsang, H. F., & Wong, S. C. (2024). Comprehensive review of COVID-19: Epidemiology, pathogenesis, advancement in diagnostic and detection techniques, and post-pandemic treatment strategies. International Journal of Molecular Sciences, 25(15), 8155.
Cocherie, T., Zafilaza, K., Leducq, V., Marot, S., Calvez, V., Marcelin, A. G., & Todesco, E. (2022). Epidemiology and characteristics of SARS-CoV-2 variants of concern: The impacts of the spike mutations. Microorganisms, 11(1), 30.
Cossio-Pérez, R., Palma, J., & Pierdominici-Sottile, G. (2017). Consistent principal component modes from molecular dynamics simulations of proteins. Journal of Chemical Information and Modeling, 57(4), 826–834.
da Costa, C. H. S., de Freitas, C. A. B., Dos Santos, A. M., da Silva de Souza, C. G., Silva, J. R. A., Lameira, J., Moliner, V., & Skaf, M. S. (2025). Conformational dynamics and binding interactions of SARS-CoV-2 spike protein variants: Omicron, XBB.1.9.2, and EG.5. Journal of Chemical Information and Modeling, 65(14), 7651–7667.
Dadonaite, B., Harari, S., Larsen, B. B., Kampman, L., Harteloo, A., Elias-Warren, A., Chu, H. Y., & Bloom, J. D. (2025). Spike mutations that affect the function and antigenicity of recent KP.3.1.1-like SARS-CoV-2 variants. Journal of Virology, 99(11), e0142325.
Eisenhaber, F., Lijnzaad, P., Argos, P., Sander, C. & Scharf, M. (1995). The double cubic lattice method: Efficient approaches to numerical integration of surface area and volume and to dot surface contouring of molecular assemblies. Journal of Computational Chemistry, 16, 273–284.
Faraji, N., Zeinali, T., Joukar, F., Aleali, M. S., Eslami, N., Shenagari, M., & Mansour-Ghanaei, F. (2024). Mutational dynamics of SARS-CoV-2: Impact on future COVID-19 vaccine strategies. Heliyon, 10(9), e30208.
Feng, Y., Su, Q., Li, L., He, X., Niu, P., Guo, X., Zhao, X., Tang, J., Jia, Z., Wang, J., Wu, C., Xia, B., Chen, Z., Wu, Y., Yang, J., Chen, S., Chen, C., Wang, S., & Dong, X. (2024). Genomic surveillance for SARS-CoV-2 variants: Dominance of XBB replacement – China, January–June 2023. China CDC Weekly, 6(15), 324–331.
Fourati, S., & Loubet, P. (2026). SARS-CoV-2 BA.3.2: Epidemiological trends and implications for prophylactic antibodies. New Microbes and New Infections, 70, 101727.
Gangavarapu, K., Latif, A. A., Mullen, J. L., Alkuzweny, M., Hufbauer, E., Tsueng, G., Haag, E., Zeller, M., Aceves, C. M., Zaiets, K., Cano, M., Zhou, X., Qian, Z., Sattler, R., Matteson, N. L., Levy, J. I., Lee, R. T. C., Freitas, L., Maurer-Stroh, S., GISAID Core and Curation Team, … Hughes, L. D. (2023). Outbreak.info genomic reports: Scalable and dynamic surveillance of SARS-CoV-2 variants and mutations. Nature Methods, 20(4), 512–522.
Gohlke, H., & Case, D. A. (2004). Converging free energy estimates: MM-PB(GB)SA studies on the protein-protein complex Ras-Raf. Journal of Computational Chemistry, 25(2), 238–250.
Grantham, R. (1974). Amino acid difference formula to help explain protein evolution. Science, 185(4154), 862–864.
Guan, X., Yang, Y., & Du, L. (2023). Advances in SARS-CoV-2 receptor-binding domain-based COVID-19 vaccines. Expert Review of Vaccines, 22(1), 422–439.
Guo, C., Yu, Y., Liu, J., Jian, F., Yang, S., Song, W., Yu, L., Shao, F., & Cao, Y. (2025). Antigenic and virological characteristics of SARS-CoV-2 variants BA.3.2, XFG, and NB.1.8.1. The Lancet. Infectious Diseases, 25(7), e374–e377.
Huang, J., Rauscher, S., Nawrocki, G., Ran, T., Feig, M., de Groot, B. L., Grubmüller, H., & MacKerell Jr., A. D. (2017). CHARMM36m: An improved force field for folded and intrinsically disordered proteins. Nature Methods, 14(1), 71–73.
Huang, Y., Yang, C., Xu, X. F., Xu, W., & Liu, S. W. (2020). Structural and functional properties of SARS-CoV-2 spike protein: Potential antivirus drug development for COVID-19. Acta Pharmacologica Sinica, 41(9), 1141–1149.
Hwang, Y. C., Lu, R. M., Su, S. C., Chiang, P. Y., Ko, S. H., Ke, F. Y., Liang, K. H., Hsieh, T. Y., & Wu, H. C. (2022). Monoclonal antibodies for COVID-19 therapy and SARS-CoV-2 detection. Journal of Biomedical Science, 29, 1.
Islam M. A. (2023). A review of SARS-CoV-2 variants and vaccines: Viral properties, mutations, vaccine efficacy, and safety. Infectious Medicine, 2(4), 247–261.
Islam, M. A., Kaifa, F. H., Chandran, D., Bhattacharya, M., Chakraborty, C., Bhattacharya, P., & Dhama, K. (2023). XBB.1.5: a new threatening SARS-CoV-2 Omicron subvariant. Frontiers in Microbiology, 14, 1154296.
Jawad, B., Adhikari, P., Podgornik, R., & Ching, W. Y. (2023). Impact of BA.1, BA.2, and BA.4/BA.5 Omicron mutations on therapeutic monoclonal antibodies. Computers in Biology and Medicine, 167, 107576.
John, O. O., Olabode, O. N., Lucero-Prisno Iii, D. E., Adebimpe, O. T., & Singh, A. (2023). XBB.1.16 Omicron subvariant rise to a variant of interest: Implications for global alertness and preparedness. Journal of Taibah University Medical Sciences, 18(6), 1285–1287.
Kung, Y. A., Chuang, C. H., Chen, Y. C., Yang, H. P., Li, H. C., Chen, C. L., Janapatla, R. P., Chen, C. J., Shih, S. R., & Chiu, C. H. (2025). Worldwide SARS-CoV-2 Omicron variant infection: Emerging sub-variants and future vaccination perspectives. Journal of the Formosan Medical Association, 124(7), 592–599.
Li, W. H., Wu, C. I., & Luo, C. C. (1984). Nonrandomness of point mutation as reflected in nucleotide substitutions in pseudogenes and its evolutionary implications. Journal of Molecular Evolution, 21(1), 58–71.
Liu, C., Zhou, D., Dijokaite-Guraliuc, A., Supasa, P., Duyvesteyn, H. M. E., Ginn, H. M., Selvaraj, M., Mentzer, A. J., Das, R., de Silva, T. I., Ritter, T. G., Plowright, M., Newman, T. A. H., Stafford, L., Kronsteiner, B., Temperton, N., Lui, Y., Fellermeyer, M., Goulder, P., Klenerman, P., … Screaton, G. R. (2024a). A structure-function analysis shows SARS-CoV-2 BA.2.86 balances antibody escape and ACE2 affinity. Cell Reports. Medicine, 5(5), 101553.
Liu, W., Huang, Z., Xiao, J., Wu, Y., Xia, N., & Yuan, Q. (2024b). Evolution of the SARS-CoV-2 Omicron variants: Genetic impact on viral fitness. Viruses, 16(2), 184.
Looi M. K. (2023). What do we know about the Arcturus XBB.1.16 subvariant? British Medical Journal, 381, 1074.
Lu, Y., Shen, F., He, W., Li, A., Li, M., Feng, X., Zheng, Y., & Pang, W. (2023). HR121 targeting HR2 domain in S2 subunit of spike protein can serve as a broad-spectrum SARS-CoV-2 inhibitor via intranasal administration. Acta Pharmaceutica Sinica, B, 13(8), 3339–3351.
Magazine, N., Zhang, T., Bungwon, A. D., McGee, M. C., Wu, Y., Veggiani, G., & Huang, W. (2024). Immune epitopes of SARS-CoV-2 spike protein and considerations for universal vaccine development. ImmunoHorizons, 8(3), 214–226.
Mannar, D., Saville, J. W., Poloni, C., Zhu, X., Bezeruk, A., Tidey, K., Ahmed, S., Tuttle, K. S., Vahdatihassani, F., Cholak, S., Cook, L., Steiner, T. S., & Subramaniam, S. (2024). Altered receptor binding, antibody evasion and retention of T cell recognition by the SARS-CoV-2 XBB.1.5 spike protein. Nature Communications, 15(1), 1854.
Markov, P. V., Ghafari, M., Beer, M., Lythgoe, K., Simmonds, P., Stilianakis, N. I., & Katzourakis, A. (2023). The evolution of SARS-CoV-2. Nature Reviews. Microbiology, 21(6), 361–379.
Mellis, I. A., Wu, M., Hong, H., Tzang, C. C., Bowen, A., Wang, Q., Gherasim, C., Pierce, V. M., Shah, J. G., Purpura, L. J., Yin, M. T., Gordon, A., Guo, Y., & Ho, D. D. (2025). Antibody evasion and receptor binding of SARS-CoV-2 LP.8.1.1, NB.1.8.1, XFG, and related subvariants. Cell Reports, 44(10), 116440.
Mengist, H. M., Kombe Kombe, A. J., Mekonnen, D., Abebaw, A., Getachew, M., & Jin, T. (2021). Mutations of SARS-CoV-2 spike protein: Implications on immune evasion and vaccine-induced immunity. Seminars in Immunology, 55, 101533.
Miller, B. R., 3rd, McGee Jr., T. D., Swails, J. M., Homeyer, N., Gohlke, H., & Roitberg, A. E. (2012). MMPBSA.py: An efficient program for end-state free energy calculations. Journal of Chemical Theory and Computation, 8(9), 3314–3321.
Murmu, N., Sarkar, M., Dey, S., Manna, R., Roy, S., Mondal, T., Halder, S., Bhattacharjee, N., Dash, S. K., & Giri, B. (2024). Efficacy and limitations of repurposed drugs and vaccines for COVID-19. Journal of Medicine, Surgery, and Public Health, 2, 100041.
Naveed Siddiqui, A., Musharaf, I., & Gulumbe, B. H. (2025). The JN.1 variant of COVID-19: Immune evasion, transmissibility, and implications for global health. Therapeutic Advances in Infectious Disease, 12, 20499361251314763.
Naveed, N., Ahmad, K., Majeed, H., Qureshi, K., Ahmad, I., Awan, M. F., Iftikhar, T., Ahmad, S., Noreen, F., Amin, M. A., & Batool, H. (2024). The global impact of COVID-19: A comprehensive analysis of its effects on various aspects of life. Toxicology Research, 13(2), tfae045.
Ou, X., Liu, Y., Lei, X., Li, P., Mi, D., Ren, L., Guo, L., Guo, R., Chen, T., Hu, J., Xiang, Z., Mu, Z., Chen, X., Chen, J., Hu, K., Jin, Q., Wang, J., & Qian, Z. (2020). Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nature Communications, 11(1), 1620.
Pak, A., Adegboye, O. A., Adekunle, A. I., Rahman, K. M., McBryde, E. S., & Eisen, D. P. (2020). Economic consequences of the COVID-19 outbreak: The need for epidemic preparedness. Frontiers in Public Health, 8, 241.
Pal, M., Berhanu, G., Desalegn, C., & Kandi, V. (2020). Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): An update. Cureus, 12(3), e7423.
Parsons, R. J., & Acharya, P. (2023). Evolution of the SARS-CoV-2 Omicron spike. Cell Reports, 42(12), 113444.
Parums, D. V. (2023). Editorial: A rapid global increase in COVID-19 is due to the emergence of the EG.5 (Eris) subvariant of Omicron SARS-CoV-2. Medical Science Monitor, 29, e942244.
Patterson, L. D., Elsharkawy, A., Jahantigh, H. R., Nabi, Z., Stone, S., & Kumar, M. (2025). Pathogenicity of SARS-CoV-2 Omicron subvariants JN.1, KP.2, and EG.5.1 in K18-hACE2 transgenic mice. Viruses, 17(9), 1177.
Peka, M., & Balatsky, V. (2023). The impact of mutation sets in receptor-binding domain of SARS-CoV-2 variants on the stability of RBD-ACE2 complex. Future Virology, 18(4), 225–242.
Planas, D., Staropoli, I., Michel, V., Lemoine, F., Donati, F., Prot, M., Porrot, F., Guivel-Benhassine, F., Jeyarajah, B., Brisebarre, A., Dehan, O., Avon, L., Bolland, W. H., Hubert, M., Buchrieser, J., Vanhoucke, T., Rosenbaum, P., Veyer, D., Péré, H., Lina, B., … Schwartz, O. (2024). Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion. Nature Communications, 15(1), 2254.
Pourriyahi, H., Hajizadeh, N., Khosravi, M., Pourriahi, H., Soleimani, S., Hosseini, N. S., Mohammad, A. P., & Goodarzi, A. (2024). New variants of COVID-19 (XBB.1.5 and XBB.1.16, the "Arcturus"): A review of highly questioned concerns, a brief comparison between different peaks in the COVID-19 pandemic, with a focused systematic review on expert recommendations for prevention, vaccination, and treatment measures in the general population and at-risk groups. Immunity, Inflammation and Disease, 12(6), e1323.
Rabaan, A. A., Alenazy, M. F., Alshehri, A. A., Alshahrani, M. A., Al-Subaie, M. F., Alrasheed, H. A., Al Kaabi, N. A., Thakur, N., Bouafia, N. A., Alissa, M., Alsulaiman, A. M., AlBaadani, A. M., Alhani, H. M., Alhaddad, A. H., Alfouzan, W. A., Ali, B. M. A., Al-Abdulali, K. H., Khamis, F., Bayahya, A., Al Fares, M. A., … Dhawan, M. (2023). An updated review on pathogenic coronaviruses (CoVs) amid the emergence of SARS-CoV-2 variants: A look into the repercussions and possible solutions. Journal of Infection and Public Health, 16(11), 1870–1883.
Rathore, J. S., & Ghosh, C. (2020). Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a newly emerged pathogen: An overview. Pathogens and Disease, 78(6), ftaa042.
Saadi, F., Pal, D., & Sarma, J. D. (2021). Spike glycoprotein is central to coronavirus pathogenesis-parallel between m-CoV and SARS-CoV-2. Annals of Neurosciences, 28(3–4), 201–218.
Saha, A., Ghosh Roy, S., Dwivedi, R., Tripathi, P., Kumar, K., Nambiar, S. M., & Pathak, R. (2025). Beyond the pandemic era: Recent advances and efficacy of SARS-CoV-2 vaccines against emerging variants of concern. Vaccines, 13(4), 424.
Saladino, V., Algeri, D., & Auriemma, V. (2020). The psychological and social impact of Covid-19: New perspectives of well-being. Frontiers in Psychology, 11, 577684.
Sali, A., & Blundell, T. L. (1993). Comparative protein modelling by satisfaction of spatial restraints. Journal of Molecular Biology, 234(3), 779–815.
Santo, K., Favaro, L., & Martins, E. (2025). Following the pandemic: Exploring long COVID's impact on global health through the World Heart Federation Global COVID-19 Study. Global Heart, 20(1), 79.
Sarker, R., Roknuzzaman, A. S. M., Hossain, M. J., Bhuiyan, M. A., & Islam, M. R. (2023). The WHO declares COVID-19 is no longer a public health emergency of international concern: benefits, challenges, and necessary precautions to come back to normal life. International Journal of Surgery, 109(9), 2851–2852.
Shakya, M., Ma, K. C., Hughes, L. J., Boehm, A. B., Cook, P. W., Cornforth, D. M., Gardner, M., Goraichuk, I. V., Harcourt, J. L., Hicks, H., Johnson, M., Kelleher, A., Reese, H. E., Sabin, S. J., Smith, T. C., Tamin, A., Wolfe, M. K., Silk, B. J., Paden, C. R., … MacNeil, A. (2026). Early detection and surveillance of the SARS-CoV-2 variant BA.3.2 – worldwide, November 2024–February 2026. MMWR and Morbidity and Mortality Weekly Report, 75, 130–137.
Sharma, T., Gerstman, B., & Chapagain, P. (2023). Distinctive features of the XBB.1.5 and XBB.1.16 spike protein receptor-binding domains and their roles in conformational changes and angiotensin-converting enzyme 2 binding. International Journal of Molecular Sciences, 24(16), 12586.
Shi, J., Zhao, X., Jin, X., Li, J., Liu, Y., Liu, H., Hu, Y. F., Chen, Z., Xiao, Y., Wang, L., Wang, Y., He, Y., Chai, Y., Hu, B., Shuai, H., Wang, Y., Li, X., Jiang, S., Zhang, Y., Zhang, X., … Chu, H. (2025). Pathogenicity, virological features, and immune evasion of SARS-CoV-2 JN.1-derived variants including JN.1.7, KP.2, KP.3, and KP.3.1.1. Nature Communications, 16(1), 11002.
Sil, D., Gautam, S., Saxena, S., Joshi, S., Kumar, D., Mehta, A., Jindal, P., Sharma, S., Pandey, P., Diksha, & Singh, A. (2024). Comprehensive analysis of Omicron subvariants: EG.5 rise, vaccination strategies, and global impact. Current Drug Targets, 25(8), 517–525.
Soares, V. C., Moreira, I. B. G., & Dias, S. S. G. (2025). SARS-CoV-2 infection and antiviral strategies: Advances and limitations. Viruses, 17(8), 1064.
Souza, U. J. B., Spilki, F. R., Tanuri, A., Roehe, P. M., & Campos, F. S. (2025). Two years of SARS-CoV-2 Omicron genomic evolution in Brazil (2022–2024): Subvariant tracking and assessment of regional sequencing efforts. Viruses, 17(1), 64.
Spiess, K., Petrillo, M., Paracchini, V., Leoni, G., Lassaunière, R., Polacek, C., Marving, E. L., Larsen, N. B., Gunalan, V., Ring, A., Bull, M., Buttinger, G., Veneri, C., Suffredini, E., La Rosa, G., Corbisier, P., Querci, M., Rasmussen, M., & Marchini, A. (2024). Development of new RT-PCR assays for the specific detection of BA.2.86 SARS-CoV-2 and its descendent sublineages. The Science of the Total Environment, 954, 176365.
Sun, M., Yan, S., Cao, T., & Zhang, J. (2024). The impact of COVID-19 pandemic on the world's major economies: based on a multi-country and multi-sector CGE model. Frontiers in Public Health, 12, 1338677.
Tamura, T., Ito, J., Uriu, K., Zahradnik, J., Kida, I., Anraku, Y., Nasser, H., Shofa, M., Oda, Y., Lytras, S., Nao, N., Itakura, Y., Deguchi, S., Suzuki, R., Wang, L., Begum, M. M., Kita, S., Yajima, H., Sasaki, J., Sasaki-Tabata, K., … Sato, K. (2023). Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants. Nature Communications, 14(1), 2800.
Tradigo, G., Das, J. K., Vizza, P., Roy, S., Guzzi, P. H., & Veltri, P. (2023). Strategies and trends in COVID-19 vaccination delivery: What we learn and what we may use for the future. Vaccines, 11(9), 1496.
Traore, A., Charniga, K., Grellet, S., Terpant, G., Da Cruz, H., Lamy, A., Thomas, N., Gbaguidi, G., Mercier, A., Prudhomme, J., Visseaux, B., Vieillefond, V., Haim-Boukobza, S., Giannoli, J. M., RELAB Study Group, Laboratory group, Castro-Alvarez, J., Kouamen, A. C., Rameix-Welti, M. A., Beirrera-Ibraim, S., … Members of the RELAB Study Group (2025). Monitoring SARS-CoV-2 variants with complementary surveillance systems: risk evaluation of the Omicron JN.1 variant in France, August 2023 to January 2024. Euro Surveillance: Bulletin Europeen sur les Maladies Transmissibles, 30(1), 2400293.
Tsueng, G., Mullen, J. L., Alkuzweny, M., Cano, M., Rush, B., Haag, E., Lin, J., Welzel, D. J., Zhou, X., Qian, Z., Latif, A. A., Hufbauer, E., Zeller, M., Andersen, K. G., Wu, C., Su, A. I., Gangavarapu, K., & Hughes, L. D. (2023). Outbreak.info Research Library: A standardized, searchable platform to discover and explore COVID-19 resources. Nature Methods, 20(4), 536–540.
Uludağ, M., Incitti, R., Gao, X., Heeney, J. L., Gojobori, T., & Alam, I. (2024). Global surveillance of emerging SARS-CoV-2 variants. Bulletin of the World Health Organization, 102(6), 374–374A.
Uraki, R., Korber, B., Diamond, M. S., & Kawaoka, Y. (2026). SARS-CoV-2 variants: Biology, pathogenicity, immunity and control. Nature Reviews, Microbiology, 24(1), 8–28.
Uriu, K., Okumura, K., Uwamino, Y., Chen, L., Tolentino, J. E., Asakura, H., Nagashima, M., Sadamasu, K., Yoshimura, K., Ito, J., Sato, K., & Genotype to Phenotype Japan (G2P-Japan) Consortium (2025). Virological characteristics of the SARS-CoV-2 NB.1.8.1 variant. The Lancet. Infectious Diseases, 25(8), e443.
Uzer, F., Erendor, F., & Sanlioglu, S. (2026). SARS-CoV-2 variants and immune evasion: Mapping the future of vaccine design. Reviews in Medical Virology, 36(3), e70157.
Valdés-Tresanco, M. S., Valdés-Tresanco, M. E., Valiente, P. A., & Moreno, E. (2021). gmx_MMPBSA: A new tool to perform end-state free energy calculations with GROMACS. Journal of Chemical Theory and Computation, 17(10), 6281–6291.
Veneri, C., Brandtner, D., Mancini, P., Bonanno Ferraro, G., Iaconelli, M., Suffredini, E., Petrillo, M., Leoni, G., Paracchini, V., Gawlik, B. M., Marchini, A., SARI Network, & La Rosa, G. (2024). Tracking the spread of the BA.2.86 lineage in Italy through wastewater analysis. Food and Environmental Virology, 16(4), 449–457.
Verma, A., Manojkumar, A., Dhasmana, A., Tripathi, M. K., Jaggi, M., Chauhan, S. C., Chauhan, D. S., & Yallapu, M. M. (2024). Recurring SARS-CoV-2 variants: An update on post-pandemic, co-infections and immune response. Nanotheranostics, 8(2), 247–269.
Walls, A. C., Park, Y. J., Tortorici, M. A., Wall, A., McGuire, A. T., & Veesler, D. (2020). Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell, 181(2), 281–292.e6.
Wang, Q., Zhang, Y., Wu, L., Niu, S., Song, C., Zhang, Z., Lu, G., Qiao, C., Hu, Y., Yuen, K. Y., Wang, Q., Zhou, H., Yan, J., & Qi, J. (2020). Structural and functional basis of SARS-CoV-2 entry by using human ACE2. Cell, 181(4), 894–904.e9.
Wang, X., Lu, L., & Jiang, S. (2023). SARS-CoV-2 Omicron subvariant BA.2.86: Limited potential for global spread. Signal Transduction and Targeted Therapy, 8(1), 439.
Waterhouse, A., Bertoni, M., Bienert, S., Studer, G., Tauriello, G., Gumienny, R., Heer, F. T., de Beer, T. A. P., Rempfer, C., Bordoli, L., Lepore, R., & Schwede, T. (2018). SWISS-MODEL: Homology modelling of protein structures and complexes. Nucleic Acids Research, 46(W1), W296–W303.
Weng, G., Wang, E., Wang, Z., Liu, H., Zhu, F., Li, D., & Hou, T. (2019). HawkDock: A web server to predict and analyze the protein-protein complex based on computational docking and MM/GBSA. Nucleic Acids Research, 47(W1), W322–W330.
Yadav, S., Zaman, K., Bashyal, P., Bhatta, R., Bhandari, S., Mohanty, A., & Sah, R. (2023). Newer emerging SARS-COV2 variant: Omicron EG.5. Annals of Medicine and Surgery (2012), 85(12), 5845–5846.
Yaghoubi, A., Amel Jamehdar, S., Movaqar, A., Milani, N., & Soleimanpour, S. (2021). An effective drug against COVID-19: reality or dream? Expert Review of Respiratory Medicine, 15(4), 505–518.
Yamasoba, D., Uriu, K., Plianchaisuk, A., Kosugi, Y., Pan, L., Zahradnik, J., Genotype to Phenotype Japan (G2P-Japan) Consortium, Ito, J., & Sato, K. (2023). Virological characteristics of the SARS-CoV-2 omicron XBB.1.16 variant. The Lancet. Infectious Diseases, 23(6), 655–656.
Yang, S., Yu, Y., Jian, F., Song, W., Yisimayi, A., Chen, X., Xu, Y., Wang, P., Wang, J., Yu, L., Niu, X., Wang, J., Xiao, T., An, R., Wang, Y., Gu, Q., Shao, F., Jin, R., Shen, Z., Wang, Y., … Cao, Y. (2023). Antigenicity and infectivity characterisation of SARS-CoV-2 BA.2.86. The Lancet, Infectious Diseases, 23(11), e457–e459.
Yang, S., Yu, Y., Xu, Y., Jian, F., Song, W., Yisimayi, A., Wang, P., Wang, J., Liu, J., Yu, L., Niu, X., Wang, J., Wang, Y., Shao, F., Jin, R., Wang, Y., & Cao, Y. (2024). Fast evolution of SARS-CoV-2 BA.2.86 to JN.1 under heavy immune pressure. The Lancet. Infectious Diseases, 24(2), e70–e72.
Zabidi, N. Z., Liew, H. L., Farouk, I. A., Puniyamurti, A., Yip, A. J. W., Wijesinghe, V. N., Low, Z. Y., Tang, J. W., Chow, V. T. K., & Lal, S. K. (2023). Evolution of SARS-CoV-2 variants: implications on immune escape, vaccination, therapeutic and diagnostic strategies. Viruses, 15(4), 944.
Zhang, L., Chen, N., Eichmann, A., Nehlmeier, I., Moldenhauer, A. S., Stankov, M. V., Happle, C., Dopfer-Jablonka, A., Behrens, G. M. N., Hoffmann, M., & Pöhlmann, S. (2026). Epidemiological and virological update on the emerging SARS-CoV-2 variant BA.3.2. The Lancet, Infectious Diseases, 26(1), e1–e2.
Zhang, Q. E., Lindenberger, J., Parsons, R. J., Thakur, B., Parks, R., Park, C. S., Huang, X., Sammour, S., Janowska, K., Spence, T. N., Edwards, R. J., Martin, M., Williams, W. B., Gobeil, S., Montefiori, D. C., Korber, B., Saunders, K. O., Haynes, B. F., Henderson, R., & Acharya, P. (2024). SARS-CoV-2 Omicron XBB lineage spike structures, conformations, antigenicity, and receptor recognition. Molecular Cell, 84(14), 2747–2764.e7.
Zhang, X., Jiang, L., Weng, G., Shen, C., Zhang, O., Liu, M., Zhang, C., Gu, S., Wang, J., Wang, X., Du, H., Zhang, H., Zhang, K., Wang, E., & Hou, T. (2025). HawkDock version 2: An updated web server to predict and analyze the structures of protein-protein complexes. Nucleic Acids Research, 53(W1), W306–W315.
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons «Attribution» 4.0 License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
