Molecular dynamics simulations of the spike trimeric ectodomain of the SARS-CoV-2 Omicron variant: structural relationships with infectivity, evasion to immune system and transmissibility

References

• 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. In SoftwareX, 1–2, 19–25. https://doi.org/10.1016/j.softx.2015.06.001
   Google Scholar
• Amadei, A., Linssen, A. B. M., & Berendsen, H. J. C. (1993). Essential dynamics of proteins. Proteins: Structure, Function, and Genetics, 17(4), 412–425. https://doi.org/10.1002/prot.340170408
   PubMed Web of Science ®Google Scholar
• Banoun, H. (2021). Evolution of SARS-CoV-2: Review of mutations, role of the host immune system. Nephron, 145(4), 392–403.
   PubMed Web of Science ®Google Scholar
• Bertoni, M., Kiefer, F., Biasini, M., Bordoli, L., & Schwede, T. (2017). Modeling protein quaternary structure of homo- and hetero-oligomers beyond binary interactions by homology. Scientific Reports, 7(1), 1–15. https://doi.org/10.1038/s41598-017-09654-8
   PubMedGoogle Scholar
• Bienert, S., Waterhouse, A., de Beer, T. A. P., Tauriello, G., Studer, G., Bordoli, L., & Schwede, T. (2017). The SWISS-MODEL Repository—new features and functionality. Nucleic Acids Research, 45(D1), D313–D319.
   PubMed Web of Science ®Google Scholar
• Cai, Y., Zhang, J., Xiao, T., Lavine, C. L., Rawson, S., Peng, H., Zhu, H., Anand, K., Tong, P., Gautam, A., Lu, S., Sterling, S. M., Walsh, R. M., Jr., Rits-Volloch, S., Lu, J., Wesemann, D. R., Yang, W., Seaman, M. S., & Chen, B. (2021). Structural basis for enhanced infectivity and immune evasion of SARS-CoV-2 variants. Science, 373(6555), 642–648. https://doi.org/10.1126/science.abi9745[Mismatch
   PubMed Web of Science ®Google Scholar
• Casadevall, A., Henderson, J. P., Joyner, M. J., & Pirofski, L.-A. (2021). SARS-CoV-2 variants and convalescent plasma: Reality, fallacies, and opportunities. Journal of Clinical Investigation, 131(7), 1-3. https://doi.org/10.1172/JCI148832
   Web of Science ®Google Scholar
• Chan, W.-E., Chuang, C.-K., Yeh, S.-H., Chang, M.-S., & Chen, S. S.-L. (2006). Functional characterization of heptad repeat 1 and 2 mutants of the spike protein of severe acute respiratory syndrome coronavirus. Journal of Virology, 80(7), 3225–3237.
   PubMed Web of Science ®Google Scholar
• Chen, C., Boorla, V. S., Banerjee, D., Chowdhury, R., Cavener, V. S., Nissly, R. H., Gontu, A., Boyle, N. R., Vandegrift, K., Nair, M. S., Kuchipudi, S. V., & Maranas, C. D. (2021). Computational prediction of the effect of amino acid changes on the binding affinity between SARS-CoV-2 spike RBD and human ACE2. Proceedings of the National Academy of Sciences, 118(42), 1-10. https://doi.org/10.1073/pnas.2106480118[Mismatch
   Web of Science ®Google Scholar
• Chen, J., Wang, R., Wang, M., & Wei, G.-W. (2020). Mutations strengthened SARS-CoV-2 infectivity. Journal of Molecular Biology, 432(19), 5212–5226.
   PubMed Web of Science ®Google Scholar
• GISAID. (2022). Genomic epidemiology of SARS-CoV-2 with subsampling focused globally over the past 6 months. GISAID NextStrain. https://www.gisaid.org/phylodynamics/global/nextstrain/
   Google Scholar
• Gobeil, S. M.-C., Henderson, R., Stalls, V., Janowska, K., Huang, X., May, A., Speakman, M., Beaudoin, E., Manne, K., Li, D., Parks, R., Barr, M., Deyton, M., Martin, M., Mansouri, K., Edwards, R. J., Eaton, A., Montefiori, D. C., Sempowski, G. D., … Acharya, P. (2022). Structural diversity of the SARS-CoV-2 Omicron spike. Molecular Cell, 82(11), 2050–2068.e6.
   PubMed Web of Science ®Google Scholar
• Gobeil, S. M.-C., Janowska, K., McDowell, S., Mansouri, K., Parks, R., Manne, K., Stalls, V., Kopp, M. F., Henderson, R., Edwards, R. J., Haynes, B. F., & Acharya, P. (2021). D614G mutation alters SARS-CoV-2 spike conformation and enhances protease cleavage at the S1/S2 junction. Cell Reports, 34(2), 108630. https://doi.org/10.1016/j.celrep.2020.108630
   PubMed Web of Science ®Google Scholar
• Grant, B. J., Rodrigues, A. P. C., ElSawy, K. M., McCammon, J. A., & Caves, L. S. D. (2006). Bio3d: An R package for the comparative analysis of protein structures. Bioinformatics (Oxford, England), 22(21), 2695–2696. https://doi.org/10.1093/bioinformatics/btl461[Mismatch
   PubMed Web of Science ®Google Scholar
• Humphrey, W., Dalke, A., & Schulten, K. (1996). VMD: Visual molecular dynamics. Journal of Molecular Graphics, 14(1), 33–38. https://doi.org/10.1016/0263-7855(96)00018-5[Mismatch
   PubMedGoogle Scholar
• Jackson, C. B., Farzan, M., Chen, B., & Choe, H. (2022). Mechanisms of SARS-CoV-2 entry into cells. Nature Reviews. Molecular Cell Biology, 23(1), 3–20. https://doi.org/10.1038/s41580-021-00418-x[Mismatch
   PubMed Web of Science ®Google Scholar
• Khan, A., Gui, J., Ahmad, W., Haq, I., Shahid, M., Khan, A. A., Shah, A., Khan, A., Ali, L., Anwar, Z., Safdar, M., Abubaker, J., Uddin, N. N., Cao, L., Wei, D.-Q., & Mohammad, A. (2021). The SARS-CoV-2 B.1.618 variant slightly alters the spike RBD-ACE2 binding affinity and is an antibody escaping variant: A computational structural perspective. RSC Advances, 11(48), 30132–30147.
   PubMed Web of Science ®Google Scholar
• Khan, A., Waris, H., Rafique, M., Suleman, M., Mohammad, A., Ali, S. S., Khan, T., Waheed, Y., Liao, C., & Wei, D.-Q. (2022). The Omicron (B.1.1.529) variant of SARS-CoV-2 binds to the hACE2 receptor more strongly and escapes the antibody response: Insights from structural and simulation data. International Journal of Biological Macromolecules, 200, 438–448. https://doi.org/10.1016/j.ijbiomac.2022.01.059
   PubMed Web of Science ®Google Scholar
• Ku, Z., Xie, X., Davidson, E., Ye, X., Su, H., Menachery, V. D., Li, Y., Yuan, Z., Zhang, X., Muruato, A. E., I Escuer, A. G., Tyrell, B., Doolan, K., Doranz, B. J., Wrapp, D., Bates, P. F., McLellan, J. S., Weiss, S. R., Zhang, N., Shi, P.-Y., & An, Z. (2021). Author correction: Molecular determinants and mechanism for antibody cocktail preventing SARS-CoV-2 escape. Nature Communications, 12(1), 4177.
   PubMed Web of Science ®Google Scholar
• Lan, J., Ge, J., Yu, J., Shan, S., Zhou, H., Fan, S., Zhang, Q., Shi, X., Wang, Q., Zhang, L., & Wang, X. (2020). Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature, 581(7807), 215–220. https://doi.org/10.1038/s41586-020-2180-5
   PubMed Web of Science ®Google Scholar
• Lindahl, E., Hess, B., & van der Spoel, D. (2001). GROMACS 3.0: A package for molecular simulation and trajectory analysis. Journal of Molecular Modeling, 7(8), 306–317. https://doi.org/10.1007/s008940100045[Mismatch
   Web of Science ®Google Scholar
• Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The impact of mutations in SARS-CoV-2 spike on viral infectivity and antigenicity. Cell, 182(5), 1284–1294.e9.
   PubMed Web of Science ®Google Scholar
• Li, Y., Wang, T., Zhang, J., Shao, B., Gong, H., Wang, Y., He, X., Liu, S., & Liu, T.-Y. (2021). Exploring the regulatory function of the N-terminal domain of SARS-CoV-2 spike protein through molecular dynamics simulation. Advanced Theory and Simulations, 4(10), 2100152.
   PubMed Web of Science ®Google Scholar
• Lubinski, B., Fernandes, M. H. V., Frazier, L., Tang, T., Daniel, S., Diel, D. G., Jaimes, J. A., & Whittaker, G. R. (2022). Functional evaluation of the P681H mutation on the proteolytic activation of the SARS-CoV-2 variant B.1.1.7 (Alpha) spike. iScience, 25(1), 103589.
   PubMed Web of Science ®Google Scholar
• Lupala, C. S., Ye, Y., Chen, H., Su, X.-D., & Liu, H. (2022). Mutations on RBD of SARS-CoV-2 Omicron variant result in stronger binding to human ACE2 receptor. Biochemical and Biophysical Research Communications, 590, 34–41.
   PubMed Web of Science ®Google Scholar
• Lv, Z., Deng, Y.-Q., Ye, Q., Cao, L., Sun, C.-Y., Fan, C., Huang, W., Sun, S., Sun, Y., Zhu, L., Chen, Q., Wang, N., Nie, J., Cui, Z., Zhu, D., Shaw, N., Li, X.-F., Li, Q., Xie, L., … Wang, X. (2020). Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody. Science (New York, N.Y.), 369(6510), 1505–1509.
   PubMed Web of Science ®Google Scholar
• Mannar, D., Saville, J. W., Zhu, X., Srivastava, S. S., Berezuk, A. M., Tuttle, K. S., Marquez, A. C., Sekirov, I., & Subramaniam, S. (2022). SARS-CoV-2 Omicron variant: Antibody evasion and cryo-EM structure of spike protein-ACE2 complex. Science, 375(6582), eabn7760. https://doi.org/10.1126/science.abn7760[Mismatch
   Web of Science ®Google Scholar
• Mansbach, R. A., Chakraborty, S., Nguyen, K., Montefiori, D. C., Korber, B., & Gnanakaran, S. (2021). The SARS-CoV-2 Spike variant D614G favors an open conformational state. Science Advances, 7(16), 1-10. https://doi.org/10.1126/sciadv.abf3671[Mismatch
   Web of Science ®Google Scholar
• Meng, B., Abdullahi, A., Ferreira, I. A. T. M., Goonawardane, N., Saito, A., Kimura, I., Yamasoba, D., Gerber, P. P., Fatihi, S., Rathore, S., Zepeda, S. K., Papa, G., Kemp, S. A., Ikeda, T., Toyoda, M., Tan, T. S., Kuramochi, J., Mitsunaga, S., Ueno, T., … Gupta, R. K., Ecuador-COVID19 Consortium. (2022). Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity. Nature, 603(7902), 706–714.
   PubMed Web of Science ®Google Scholar
• Meng, B., Datir, R., Choi, J., Bradley, J. R., Smith, K., G., C., Lee, J. H., & Gupta, R. K., CITIID-NIHR Bioresource COVID-19 Collaboration. (2022). SARS-CoV-2 spike N-terminal domain modulates TMPRSS2-dependent viral entry and fusogenicity. Cell Reports, 40(7), 111220.
   PubMed Web of Science ®Google Scholar
• Outbreak. (2022). Omicron variant report. Outbreak. https://outbreak.info/
   Google Scholar
• Ou, T., Mou, H., Zhang, L., Ojha, A., Choe, H., & Farzan, M. (2021). Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2. PLoS Pathogens, 17(1), e1009212.
   PubMed Web of Science ®Google Scholar
• Petit, C. M., Melancon, J. M., Chouljenko, V. N., Colgrove, R., Farzan, M., Knipe, D. M., & Kousoulas, K. G. (2005). Genetic analysis of the SARS-coronavirus spike glycoprotein functional domains involved in cell-surface expression and cell-to-cell fusion. Virology, 341(2), 215–230.
   PubMed Web of Science ®Google Scholar
• Pronk, S., Páll, S., Schulz, R., Larsson, P., Bjelkmar, P., Apostolov, R., Shirts, M. R., Smith, J. C., Kasson, P. M., van der Spoel, D., Hess, B., & Lindahl, E. (2013). GROMACS 4.5: A high-throughput and highly parallel open source molecular simulation toolkit. Bioinformatics (Oxford, England), 29(7), 845–854.
   PubMed Web of Science ®Google Scholar
• Puhach, O., Adea, K., Hulo, N., Sattonnet, P., Genecand, C., Iten, A., Jacquérioz, F., Kaiser, L., Vetter, P., Eckerle, I., & Meyer, B. (2022). Infectious viral load in unvaccinated and vaccinated individuals infected with ancestral, Delta or Omicron SARS-CoV-2. Nature Medicine, 28(7), 1491–1500.
   PubMed Web of Science ®Google Scholar
• Qing, E., Kicmal, T., Kumar, B., Hawkins, G. M., Timm, E., Perlman, S., & Gallagher, T. (2021). Dynamics of SARS-CoV-2 spike proteins in cell entry: Control elements in the amino-terminal domains. mBio, 12(4), e0159021.
   PubMed Web of Science ®Google Scholar
• Riediker, M., Briceno-Ayala, L., Ichihara, G., Albani, D., Poffet, D., Tsai, D.-H., Iff, S., & Monn, C. (2022). Higher viral load and infectivity increase risk of aerosol transmission for Delta and Omicron variants of SARS-CoV-2. Swiss Medical Weekly, 152, w30133.
   PubMed Web of Science ®Google Scholar
• Robertson, M. J., Tirado-Rives, J., & Jorgensen, W. L. (2015). Improved peptide and protein torsional energetics with the OPLSAA force field. Journal of Chemical Theory and Computation, 11(7), 3499–3509.
   PubMed Web of Science ®Google Scholar
• Saito, A., Irie, T., Suzuki, R., Maemura, T., Nasser, H., Uriu, K., Kosugi, Y., Shirakawa, K., Sadamasu, K., Kimura, I., Ito, J., Wu, J., Iwatsuki-Horimoto, K., Ito, M., Yamayoshi, S., Loeber, S., Tsuda, M., Wang, L., Ozono, S., … Sato, K., Genotype to Phenotype Japan (G2P-Japan) Consortium. (2022). Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation. Nature, 602(7896), 300–306.
   PubMed Web of Science ®Google Scholar
• Sakkiah, S., Guo, W., Pan, B., Ji, Z., Yavas, G., Azevedo, M., Hawes, J., Patterson, T. A., & Hong, H. (2020). Elucidating interactions between SARS-CoV-2 trimeric spike protein and ACE2 using homology modeling and molecular dynamics simulations. Frontiers in Chemistry, 8, 622632.
   PubMed Web of Science ®Google Scholar
• Schlitter, J. (1993). Estimation of absolute and relative entropies of macromolecules using the covariance matrix. Chemical Physics Letters, 215(6), 617–621. https://doi.org/10.1016/0009-2614(93)89366-P
   Web of Science ®Google Scholar
• Schrodinger. (2021). Maestro. Schrodinger. https://www.schrodinger.com/maestro
   Google Scholar
• Schroth-Diez, B., Ludwig, K., Baljinnyam, B., Kozerski, C., Huang, Q., & Herrmann, A. (2000). The role of the transmembrane and of the intraviral domain of glycoproteins in membrane fusion of enveloped viruses. Bioscience Reports, 20(6), 571–595.
   PubMed Web of Science ®Google Scholar
• Sentis, C., Billaud, G., Bal, A., Frobert, E., Bouscambert, M., Destras, G., Josset, L., Lina, B., Morfin, F., & Gaymard, A., The Covid-Diagnosis Hcl Study Group. (2022). SARS-CoV-2 omicron variant, lineage BA.1, is associated with lower viral load in nasopharyngeal samples compared to delta variant. Viruses, 14(5), 919. https://doi.org/10.3390/v14050919
   PubMed Web of Science ®Google Scholar
• Sironi, M., Hasnain, S. E., Rosenthal, B., Phan, T., Luciani, F., Shaw, M.-A., Sallum, M. A., Mirhashemi, M. E., Morand, S., & González-Candelas, F., Editors of Infection, Genetics and Evolution. (2020). SARS-CoV-2 and COVID-19: A genetic, epidemiological, and evolutionary perspective. Infection, Genetics and Evolution, 84, 104384.
   PubMed Web of Science ®Google Scholar
• Socher, E., Conrad, M., Heger, L., Paulsen, F., Sticht, H., Zunke, F., & Arnold, P. (2021). Mutations in the B.1.1.7 SARS-CoV-2 spike protein reduce receptor-binding affinity and induce a flexible link to the fusion peptide. Biomedicines, 9(5), 525–513. https://doi.org/10.3390/biomedicines9050525[Mismatch
   PubMed Web of Science ®Google Scholar
• Souza, A. S., Rivera, J. D., Almeida, V. M., Ge, P., Souza, R. F., Farah, C. S., Ulrich, H., Marana, S. R., Salinas, R. K., & Guzzo, C. R. (2020). Molecular dynamics reveals complex compensatory effects of ionic strength on the severe acute respiratory syndrome coronavirus 2 spike/human angiotensin-converting enzyme 2 interaction. The Journal of Physical Chemistry Letters, 11(24), 10446–10453.
   PubMed Web of Science ®Google Scholar
• Souza, A. S., Amorim, V. M. F., Guardia, G. D. A., Santos, F. F. d., Ulrich, H., Galante, P. A. F., Souza, R. F. d., & Guzzo, C. R. (2022a). Severe acute respiratory syndrome Coronavirus 2 variants of concern: A perspective for emerging more transmissible and vaccine-resistant strains. Viruses, 14(4), 827–821. https://doi.org/10.3390/v14040827
   PubMed Web of Science ®Google Scholar
• Souza, A. S., Amorim, V. M. F., Guardia, G. D. A., dos Santos, F. R. C., dos Santos, F. F., de Souza, R. F., de Araujo Juvenal, G., Huang, Y., Ge, P., Jiang, Y., Li, C., Paudel, P., Ulrich, H., Galante, P. A. F., & Guzzo, C. R. (2022b). Molecular dynamics analysis of fast-spreading severe acute respiratory syndrome Coronavirus 2 variants and their effects on the interaction with human angiotensin-converting enzyme 2. ACS Omega, 7(35), 30700–30709. https://doi.org/10.1021/acsomega.1c07240
   PubMed Web of Science ®Google Scholar
• Tian, F., Tong, B., Sun, L., Shi, S., Zheng, B., Wang, Z., Dong, X., & Zheng, P. (2021). N501Y mutation of spike protein in SARS-CoV-2 strengthens its binding to receptor ACE2. eLife, 10, 1–17. https://doi.org/10.7554/eLife.69091
   Web of Science ®Google Scholar
• Van Der Spoel, D., Lindahl, E., Hess, B., Groenhof, G., Mark, A. E., Berendsen, H., & J., C. (2005). GROMACS: Fast, flexible, and free. Journal of Computational Chemistry, 26(16), 1701–1718.
   PubMed Web of Science ®Google Scholar
• 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, 183(6), 1735.
   PubMed Web of Science ®Google Scholar
• Wang, Y., Xu, C., Wang, Y., Hong, Q., Zhang, C., Li, Z., Xu, S., Zuo, Q., Liu, C., Huang, Z., & Cong, Y. (2021). Conformational dynamics of the Beta and Kappa SARS-CoV-2 spike proteins and their complexes with ACE2 receptor revealed by cryo-EM. Nature Communications, 12(1), 7345.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• WHO. (2022). WHO Coronavirus (COVID-19) dashboard. World Health Organization. https://covid19.who.int
   Google Scholar
• Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. A., Hsieh, C.-L., Abiona, O., Graham, B. S., & McLellan, J. S. (2020). Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science, 367(6483), 1260–1263.
   PubMed Web of Science ®Google Scholar
• Xia, S., Wen, Z., Wang, L., Lan, Q., Jiao, F., Tai, L., Wang, Q., Sun, F., Jiang, S., Lu, L., & Zhu, Y. (2021). Structure-based evidence for the enhanced transmissibility of the dominant SARS-CoV-2 B.1.1.7 variant (Alpha). Cell Discovery, 7(1), 109.
   PubMed Web of Science ®Google Scholar
• Xia, S., Zhu, Y., Liu, M., Lan, Q., Xu, W., Wu, Y., Ying, T., Liu, S., Shi, Z., Jiang, S., & Lu, L. (2020). Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain in spike protein. Cellular & Molecular Immunology, 17(7), 765–767.
   PubMed Web of Science ®Google Scholar
• Xie, X., Liu, Y., Liu, J., Zhang, X., Zou, J., Fontes-Garfias, C. R., Xia, H., Swanson, K. A., Cutler, M., Cooper, D., Menachery, V. D., Weaver, S. C., Dormitzer, P. R., & Shi, P.-Y. (2021). Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera. Nature Medicine, 27(4), 620–621.
   PubMed Web of Science ®Google Scholar
• Yang, Y., & Du, L. (2021). SARS-CoV-2 spike protein: A key target for eliciting persistent neutralizing antibodies [Review of SARS-CoV-2 spike protein: A key target for eliciting persistent neutralizing antibodies]. Signal Transduction and Targeted Therapy, 6(1), 95.
   PubMed Web of Science ®Google Scholar
• Yurkovetskiy, L., Wang, X., Pascal, K. E., Tomkins-Tinch, C., Nyalile, T. P., Wang, Y., Baum, A., Diehl, W. E., Dauphin, A., Carbone, C., Veinotte, K., Egri, S. B., Schaffner, S. F., Lemieux, J. E., Munro, J. B., Rafique, A., Barve, A., Sabeti, P. C., Kyratsous, C. A., … Luban, J. (2020). Structural and functional analysis of the D614G SARS-CoV-2 spike protein variant. Cell, 183(3), 739–751.e8.
   PubMed Web of Science ®Google Scholar
• Yu, H., Zhao, Y., Guo, C., Gan, Y., & Huang, H. (2015). The role of proline substitutions within flexible regions on thermostability of luciferase. Biochimica et Biophysica Acta, 1854(1), 65–72.
   PubMed Web of Science ®Google Scholar
• Zhang, J., Cai, Y., Xiao, T., Lu, J., Peng, H., Sterling, S. M., Walsh, R. M., Jr., Rits-Volloch, S., Zhu, H., Woosley, A. N., Yang, W., Sliz, P., & Chen, B. (2021). Structural impact on SARS-CoV-2 spike protein by D614G substitution. Science (New York, N.Y.), 372(6541), 525–530.
   PubMed Web of Science ®Google Scholar
• Zhang, J., Xiao, T., Cai, Y., Lavine, C. L., Peng, H., Zhu, H., Anand, K., Tong, P., Gautam, A., Mayer, M. L., Walsh, R. M., Jr., Rits-Volloch, S., Wesemann, D. R., Yang, W., Seaman, M. S., Lu, J., & Chen, B. (2021). Membrane fusion and immune evasion by the spike protein of SARS-CoV-2 Delta variant. Science (New York, N.Y.), 374(6573), 1353–1360.
   PubMed Web of Science ®Google Scholar
• Zhang, L., Jackson, C. B., Mou, H., Ojha, A., Peng, H., Quinlan, B. D., Rangarajan, E. S., Pan, A., Vanderheiden, A., Suthar, M. S., Li, W., Izard, T., Rader, C., Farzan, M., & Choe, H. (2020). SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity. Nature Communications, 11(1), 6013.
   PubMed Web of Science ®Google Scholar
• Zhao, H., Lu, L., Peng, Z., Chen, L.-L., Meng, X., Zhang, C., Ip, J. D., Chan, W.-M., Chu, A. W.-H., Chan, K.-H., Jin, D.-Y., Chen, H., Yuen, K.-Y., & To, K. K.-W. (2022). SARS-CoV-2 Omicron variant shows less efficient replication and fusion activity when compared with Delta variant in TMPRSS2-expressed cells. Emerging Microbes & Infections, 11(1), 277–283.
   PubMed Web of Science ®Google Scholar
• Zhu, C., He, G., Yin, Q., Zeng, L., Ye, X., Shi, Y., & Xu, W. (2021). Molecular biology of the SARs-CoV-2 spike protein: A review of current knowledge. Journal of Medical Virology, 93(10), 5729–5741.
   PubMed Web of Science ®Google Scholar
• Zimmerman, M. I., Porter, J. R., Ward, M. D., Singh, S., Vithani, N., Meller, A., Mallimadugula, U. L., Kuhn, C. E., Borowsky, J. H., Wiewiora, R. P., Hurley, M. F. D., Harbison, A. M., Fogarty, C. A., Coffland, J. E., Fadda, E., Voelz, V. A., Chodera, J. D., & Bowman, G. R. (2021). SARS-CoV-2 simulations go exascale to predict dramatic spike opening and cryptic pockets across the proteome. Nature Chemistry, 13(7), 651–659.
   PubMed Web of Science ®Google Scholar