Monoclonal antibodies lock down SARS-CoV-2 spike

Area of Science:

• Virology
• Immunology
• Structural Biology

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly mutates, particularly in the receptor-binding domain (RBD) of its Spike protein.
• These mutations have led to the ineffectiveness of existing clinically authorized monoclonal antibodies (mAbs).

Purpose of the Study:

• To identify and characterize novel human monoclonal antibodies (mAbs) capable of neutralizing diverse SARS-CoV-2 variants.
• To elucidate the mechanism by which these new mAbs inhibit viral entry.

Main Methods:

• Isolation and characterization of human monoclonal antibodies (mAbs).
• Viral neutralization assays against multiple SARS-CoV-2 variants.
• Structural studies to determine the binding mode of mAbs to the Spike protein RBD.

Main Results:

• Discovery of potent human mAbs that neutralize all tested SARS-CoV-2 variants.
• Demonstration that these mAbs function by stabilizing the Spike protein RBD in a 'downward' conformation.
• This conformational lock prevents the RBD from engaging with the host cell receptor (ACE2).

Conclusions:

• The identified human mAbs offer a promising therapeutic strategy against current and potentially future SARS-CoV-2 variants.
• Targeting the RBD in a stabilized downward conformation represents a viable approach to overcome viral immune evasion.