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A Novel Antibody Against the Non-Receptor-Binding Domain Region of Middle East Respiratory Syndrome Coronavirus Spike
So-Young Lee1, Hye-Min Woo1, Hyunbum Jeon2
1Division of Emerging Virus and Vector Research, Center for Emerging Virus Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju-si, Republic of Korea.
Abstract:
The Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in 2012 and has since spread worldwide. To date, no vaccines or therapeutics against MERS-CoV have been approved for clinical use. The spike protein of MERS-CoV facilitates attachment and fusion with target cell membranes. Therefore, inhibiting S protein attachment represents a key therapeutic strategy for treating early MERS-CoV infection. Herein, we present 7 human neutralizing antibodies (KNIH-58, -68, -72, -78, -88, -90, and -95) against MERS-CoV. KNIH-58 and -68 bound to the receptor-binding subdomain (RBD) of the spike protein, while the other 5 monoclonal antibodies did not. KNIH-88, which targets the non-RBD region, exhibited potent neutralizing activities in vitro and in a transgenic mouse model, with similar results for KNIH-58. Structural analysis of KNIH-88 bound to the spike protein revealed novel epitopes in the non-RBD region. These findings may facilitate therapeutic and prophylactic antibody development against MERS-CoV.
Insights
Researchers developed seven human neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV). One antibody, KNIH-88, targets a novel region and shows potent MERS-CoV neutralization, aiding future treatment development.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 with no approved vaccines or therapeutics.
- The MERS-CoV spike (S) protein is crucial for viral entry, making it a target for therapeutic intervention.
- Inhibiting S protein attachment offers a promising strategy for early MERS-CoV infection treatment.
Purpose of the Study:
- To identify and characterize novel human neutralizing antibodies against MERS-CoV.
- To investigate the neutralizing potential of antibodies targeting different regions of the MERS-CoV spike protein.
Main Methods:
- Isolation and characterization of seven human monoclonal antibodies (mAbs) against MERS-CoV.
- Binding assays to determine antibody interaction with the spike protein's receptor-binding domain (RBD) and non-RBD regions.
- In vitro neutralization assays and in vivo studies using a transgenic mouse model.
- Structural analysis of antibody-spike protein complexes.
Main Results:
- Seven human neutralizing antibodies (KNIH-58, -68, -72, -78, -88, -90, and -95) were identified.
- KNIH-58 and -68 bound to the RBD; KNIH-88 targeted a non-RBD region.
- KNIH-88 demonstrated potent in vitro and in vivo MERS-CoV neutralizing activity.
- Structural analysis revealed novel epitopes targeted by KNIH-88 in the non-RBD region.
Conclusions:
- Novel human neutralizing antibodies against MERS-CoV have been developed.
- Antibodies targeting non-RBD regions, like KNIH-88, offer potent therapeutic potential.
- These findings support the development of new antibody-based therapies for MERS-CoV.
