9XGW

Cryo-EM structure of SARS-CoV-2 receptor binding domain in complex with CS-42 Fab (local refinement of RBD and Fv)

Summary for 9XGW

• Entry DOI: 10.2210/pdb9xgw/pdb
• EMDB information: 66860
• Descriptor: Heavy chain of CS-42 Fab, Light chain of CS-42 Fab, Spike protein S1, ... (4 entities in total)
• Functional Keywords: viral protein, antibody, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 46662.82

Authors

Kim, U.J.,Wang, D.M.,Yoon, G.Y.,Cho, H.S. (deposition date: 2025-10-31, release date: 2026-09-09)

Primary citation

Kim, D.S.,Kim, U.,Woo, H.M.,Lee, H.,Jo, E.S.,Noh, M.J.,Lee, S.Y.,Park, B.K.,Yang, J.S.,Kim, K.C.,Lee, J.Y.,Wang, D.M.,Cho, H.S.,Kim, H.J.
Broad Neutralizing Activity of Monoclonal Antibodies Against the Omicron Variants Isolated From Patients With Early Severe Acute Respiratory Syndrome Coronavirus-2.
J Med Virol, 98:e70969-e70969, 2026

PubMed Abstract: Since its emergence in 2019, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a global pandemic driven by rapid mutation and high transmissibility. Current therapeutic strategies may not effectively address the continuously evolving mutant strains, underscoring the need for treatments with broad neutralizing activity. Two monoclonal antibodies (mAbs): SR-23 and CS-42, isolated from convalescent patients infected with SARS-CoV-2 during the early phase of the 2020 pandemic, demonstrated significant neutralizing activities against a variety of variants. Specifically, SR-23 exhibited neutralizing activity against BA.5 and XBB1.5, whereas CS-42 showed efficacy against Delta, BA.1, and BA.2 variants. In addition, combining the two mAbs demonstrated improved neutralization activity. Cryo-electron microscopy (cryo-EM) structural analysis revealed that SR-23 and CS-42 bind to nonoverlapping epitopes on the SARS-CoV-2 spike protein. Furthermore, both antibodies exhibited strong therapeutic effects in K18-hACE2 mice infected with D614G, BA.2, and XBB.1.5. These findings provide insights into the development of antibody-based therapeutics targeting emerging Omicron variants and suggest that combined administration could broaden neutralizing activity.

PubMed: 42126192
DOI: 10.1002/jmv.70969

Experimental method

ELECTRON MICROSCOPY (3.2 Å)