CVR - Coronavirus Vaccines R&D Roadmap

Diaz 2025 identified an array of broadly protective antibodies that target diverse regions of the S2 region spike protein, including the Fusion Peptide (B12), downstream of the Furin Cleavage Site (B6), and the stem helix adjacent to HR2 (B13).

DH1047

Targets the Fusion Peptide to prevent viral entry

• Olukitibi 2023: Significance of conserved regions in coronavirus spike protein for developing a novel vaccine against SARS-CoV-2 infection
• Dacon 2022: Broadly neutralizing antibodies target the coronavirus fusion peptide 

COV44-62

Targets the Fusion Peptide to prevent viral entry

• Olukitibi 2023: Significance of conserved regions in coronavirus spike protein for developing a novel vaccine against SARS-CoV-2 infection
• Dacon 2022: Broadly neutralizing antibodies target the coronavirus fusion peptide
• Martinez 2021: A broadly cross-reactive antibody neutralizes and protects against sarbecovirus challenge in mice

76E1

Targets the Fusion Peptide to prevent viral entry

• Sun 2025: Anti-S2 antibodies responsible for the SARS-CoV-2 infection-induced serological cross-reactivity against MERS-CoV and MERS-related coronaviruses 

54043-5

Elicits an Fc-mediated response, and binds the HR1/Central Helix junction of multiple betacoronaviruses (e.g., SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-OC43, HCoV-HKU1.

• Johnson 2024: Discovery and characterization of a pan-betacoronavirus S2-binding antibody 

Nanobody 79C11

Binds to the HR1 region of the S2 subunit, preventing spike-mediated cell fusion. Likely interrupts interaction between HR1 and HR2. Demonstrated activity against all SARS-CoV-2 variants tested, and against SARS-CoV-1 and pangolin coronaviruses. 

• Feng 2025: A shark-derived broadly neutralizing nanobody targeting a highly conserved epitope on the S2 domain of sarbecoviruses

3D1

Binds a cryptic 6-mer motif (DVVNQN) in HR1 that adopts a type-I β-turn only during the pre-hairpin/transition state of spike, after ACE2 engagement; prevents spike-mediated cell fusion (Yan 2025). Blocks HR1-HR2 6-HB assembly; it binds HR1 fusion-core but not other spike conformations. Demonstrated inhibition of pseudovirus entry across α, β, and δ coronaviruses.

• Yan 2025: A broadly neutralizing antibody recognizes a unique epitope with a signature motif common across coronaviruses

RAY53

Binds to the Hinge Region and blocks viral entry through an Fc-mediated response

• Silva 2023: Identification of a conserved S2 epitope present on spike proteins from all highly pathogenic coronaviruses

CoVIC-154

Targets the fusion loop to prevent viral entry

• Schendel 2025: A global collaboration for systematic analysis of broad-ranging antibodies against the SARS-CoV-2 spike protein

Diaz 2025 identified an array of broadly protective antibodies that target diverse regions of the S2 region spike protein, including the Fusion Peptide (B12), downstream of the Furin Cleavage Site (B6), and the stem helix adjacent to HR2 (B13).

Schendel 2025 identified three antibodies that target the full trimeric spike protein of SARS-CoV-2, preventing viral fusion and entry; CoVIC-364, CoVIC-161, and CoVIC-210. These antibodies offer good protection across SARS-CoV-2 variants, despite weak to moderate neutralization (possibly due to spike cross-linking, FC-effector functions, and/or stabilization of the spike protein in a non-functional pre-fusion state).