9WSP

Cryo-EM structure of SARS CoV2 S protein with stabilising mutations

Summary for 9WSP

• Entry DOI: 10.2210/pdb9wsp/pdb
• EMDB information: 66202
• Descriptor: Spike glycoprotein (1 entity in total)
• Functional Keywords: spike protein, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2
• Total number of polymer chains: 1
• Total formula weight: 124189.60

Authors

Srivastava, S.,Mishra, S.,Dutta, S.,Varadarajan, R. (deposition date: 2025-09-15, release date: 2026-04-29)

Primary citation

Srivastava, S.,Kumar, S.,Mishra, S.,Rajmani, R.S.,Singh, R.,Dutta, S.,Ringe, R.P.,Varadarajan, R.
Development of a Thermostable and Broadly Neutralizing Pan-Sarbecovirus Vaccine Candidate.
Acs Infect Dis., 12:104-118, 2026

PubMed Abstract: Zoonotic spillover of sarbecoviruses to humans resulted in the SARS-CoV-1 outbreak in 2003 and the current COVID-19 pandemic caused by SARS-CoV-2. In both cases, the viral spike protein (S) is the principal target of neutralizing antibodies that prevent infection. Within the spike, the immunodominant receptor-binding domain (RBD) is the primary target of neutralizing antibodies in COVID-19 convalescent sera and vaccine recipients. We have constructed stabilized RBD derivatives of different sarbecoviruses: SARS-CoV-1 (Clade 1a), WIV-1 (Clade 1a), RaTG13 (Clade 1b), RmYN02 (Clade 2), and BtKY72 (Clade 3). Stabilization enhanced yield by 3-23-fold. The RBD derivatives were conformationally intact, as assayed by binding to multiple broadly neutralizing antibodies. The stabilized RBDs show significant enhancement in apparent , exhibit resistance to a 2-h incubation at temperatures up to 60 °C in PBS in contrast to the corresponding WT RBDs, and show prolonged stability of over 15 days at 37 °C after lyophilization. In mice immunizations, both stabilization and trimerization significantly enhanced elicited neutralization titers by ∼100-fold. The stabilized RBD cocktail elicited highly neutralizing titers against both homologous and heterologous pseudoviruses. The immunogenicity of the vaccine formulation was assessed in both naïve and SARS-CoV-2 preimmunized mice, revealing an absence of immune imprinting, thus indicating its suitability for use in future sarbecovirus-origin epidemics or pandemics.

PubMed: 41436061
DOI: 10.1021/acsinfecdis.5c00479

Experimental method

ELECTRON MICROSCOPY (4.55 Å)