LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants

Area of Science:

• Virology
• Immunology
• Drug Discovery

Background:

• Neutralizing monoclonal antibodies (mAbs) are crucial for early COVID-19 treatment, reducing hospitalization risk.
• Emerging SARS-CoV-2 variants of concern (VOC) have diminished the efficacy of some authorized mAbs.
• Development of broadly neutralizing antibodies is essential to combat viral evolution.

Approach:

• A high-throughput B-cell screening pipeline was employed to isolate novel SARS-CoV-2 antibodies.
• LY-CoV1404 (bebtelovimab), a potent antibody targeting the spike glycoprotein receptor-binding domain (RBD), was identified.
• Extensive neutralization studies were performed using authentic SARS-CoV-2 and pseudoviruses across multiple VOCs.

Key Points:

• LY-CoV1404 demonstrates potent neutralizing activity against a wide spectrum of SARS-CoV-2 variants, including Omicron (B.1.1.529) and its subvariants (e.g., BA.2).
• The antibody retains binding and neutralizing potency against viruses with common RBD mutations (K417N, L452R, E484K, N501Y).
• Structural analysis reveals a conserved epitope for LY-CoV1404, with minimal impact from key mutations like N439K and N501Y.

Conclusions:

• LY-CoV1404 exhibits broad reactivity against current and emerging SARS-CoV-2 variants.
• The antibody's conserved epitope and potent neutralizing activity support its potential as a universal therapeutic agent for COVID-19.
• LY-CoV1404 represents a significant advancement in antibody-based therapeutics against SARS-CoV-2, addressing the challenge of viral mutations.