Medica 2026
Nov 16-19, 2026 - Düsseldorf, Germany

SARS-CoV-2: From Antigens and Antibodies to Vaccine Development

SARS-CoV-2 Genomes

SARS-CoV-2 and SARS-CoV are 79%-80% homologous at the genomic level. The entire genome is ~30kb in size, and organized into 14 ORFs that code for 29 viral proteins. Two-thirds of the 5' end of the genome encodes for two overlapping polyproteins, pp1a and pp1ab. These are subsequently cleaved by two viral proteases into 16 non-structural proteins (NSPs), responsible for viral replication and transcription. Four ORFs at the 3' end of the genome encode the four structural proteins that were expected: nucleocapsid, spike, membrane and envelope proteins. These proteins mediate virion assembly and also play a role in suppression of the host immune response. A small number of accessory genes that are intermingled between the structural genes encode the accessory proteins. The role of accessory proteins is to modulate viral infection. In contrast to the structural proteins, accessory proteins are not typically part of the virion with the exception of ORF3a and ORF7a.

Genome organization of SARS-CoV-2Figure 1. SARS-CoV-2 genome organization, with functional domains shown in rectangles and the prime drug targets emphasized in the outlined box
(Source: Yang H, et al. 2021)

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SARS-CoV-2 Life Cycle

SARS-CoV-2 life cycleFigure 2. The life cycle of SARS-CoV-2, including viral entry, replication and transcription, assembly and release. (Source: Yang H, et al. 2021)

Entry
S protein binds host receptor, enabling membrane fusion and RNA release
Protein Synthesis
Host ribosomes produce viral polyproteins pp1a and pp1ab, cleaved into 16 NSPs
Replication and Transcription
NSPs form a complex to replicate and transcribe viral RNA
Assembly and Release
New viral RNA and proteins assemble into virions, released to infect new cells

SARS-CoV-2 S protein

The S protein is the principal surface protein of SARS-CoV-2 that binds and fuses with the host cell. It is multi-faceted and its complex structures in multiple conformations mediate viral entry, providing attractive vaccine and antiviral drug design targets.

S protein trimerFigure 3. Structure of the spike protein trimer.
(Source: Bai C, et al. 2022)

Mechanism of SARS-CoV-2 Spike Protein-Mediated Membrane Fusion

1. Structural Rearrangement and Function

The S protein goes through a large-scale structural transition from a metastable prefusion conformation to a postfusion conformation that mediates fusion between the viral and cellular membranes.

2. Receptor Binding Triggers Fusion

3. Conformational Changes After Binding

4. Formation of the Fusion Core

SARS-CoV-2 S protein induces membrane fusionFigure 4. A model for membrane fusion induced by the SARS-CoV-2 S protein
(Source: Jackson CB, et al. 2022)

SARS-CoV-2 Vaccine Development

SARS-CoV-2 vaccines from several technology platforms have entered clinical development or received emergency use authorization.

Inactivated whole-virus vaccines

  • Produced by chemically inactivating the virus, and formulation with adjuvants
  • Provide broad T cell epitopes but have lower immunogenicity and production challenges

  • Use purified recombinant S protein with Matrix-M adjuvant
  • Induce strong immune responses, though some mechanisms remain unclear
Protein subunit–nanoparticle vaccines

Gene therapy–based vaccines

  • Adenoviral vector and mRNA-lipid nanoparticle vaccines
  • Extremely effective, rapid development time, and advantages for large-scale manufacturing

More SARS-CoV-2 Related Resources

What We Do With Emerging SARS-CoV-2 Variants SARS-CoV-2 ADE Assay SARS-CoV-2 mRNA Vaccines SARS-CoV-2 Spike Stable Cell Line Neutralizing Neuropilin-1 (NRP1) antibodies: Trusted Tools for SARS-CoV-2 Intervention Research

References

  1. Yang H, et al. Structural biology of SARS-CoV-2 and implications for therapeutic development. Nat Rev Microbiol. 2021 Nov;19(11):685-700.
  2. Bai C, et al. Overview of SARS-CoV-2 genome-encoded proteins. Sci China Life Sci. 2022 Feb;65(2):280-294.
  3. Jackson CB, et al. Mechanisms of SARS-CoV-2 entry into cells. Nat Rev Mol Cell Biol. 2022 Jan;23(1):3-20.
  4. Hu B, et al. Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol. 2021 Mar;19(3):141-154.
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