The single-stranded, plus-sense severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2) genome encodes nonstructural replicase polyproteins as well as structural proteins such as spike (S), nucleocapsid (N), membrane (M), and envelop (E) proteins (Zhou et al., 2020). S protein is a transmembrane homotrimeric class I fusion glycoprotein; the S1 subunit binds to angiotensinconverting enzyme II (ACE2) and S2 subunit is involved in the fusion of viral and host cell membranes (Sternberg and Naujokat, 2020). The distal subunit S1 contains a receptor binding domain, whose hinge-like conformational movement is required for ACE2 receptor binding and refolding of S2 for membrane fusion (Walls et al., 2020; Wrapp et al., 2020). Accumulating evidence from convalescent COVID-19 individuals supports that S is a highly immunogenic epitope targeted by neutralizing monoclonal antibodies through adaptive immune responses mediated by CD4+ T cells (Cao et al., 2020; Grifoni et al., 2020). As such, S has been targets for vaccine design and development to prevent SARS-CoV-2 infection and rechallenge (Sternberg and Naujokat, 2020). Cao, Y., Su, B., Guo, X., Sun, W., Deng, Y., Bao, L., Zhu, Q., Zhang, X., Zheng, Y., Geng, C., et al. (2020). Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients' B Cells. Cell 182, 73-84 e16. Grifoni, A., Weiskopf, D., Ramirez, S.I., Mateus, J., Dan, J.M., Moderbacher, C.R., Rawlings, S.A., Sutherland, A., Premkumar, L., Jadi, R.S., et al. (2020). Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals. Cell 181, 1489-1501 e1415. Sternberg, A., and Naujokat, C. (2020). Structural features of coronavirus SARS-CoV-2 spike protein: Targets for vaccination. Life Sci 257, 118056. Walls, A.C., Park, Y.J., Tortorici, M.A., Wall, A., McGuire, A.T., and Veesler, D. (2020). Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell 181, 281-292 e286. Wrapp, D., Wang, N., Corbett, K.S., Goldsmith, J.A., Hsieh, C.L., Abiona, O., Graham, B.S., and McLellan, J.S. (2020). Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 367, 1260-1263. Zhou, P., Yang, X.L., Wang, X.G., Hu, B., Zhang, L., Zhang, W., Si, H.R., Zhu, Y., Li, B., Huang, C.L., et al. (2020). A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270-273.
