Multiple SARS-CoV-2 Variants Exhibit Variable Target Cell Infectivity and Ability to Evade Antibody Neutralization

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• The emergence of SARS-CoV-2 variants of concern (VOC) has intensified the COVID-19 pandemic.
• The viral spike (S) protein is crucial for host cell entry and a primary target for antibody-based therapeutics.
• Mutations in the S protein can lead to immune escape and altered viral characteristics.

Purpose of the Study:

• To characterize mutations in the spike protein of emerging SARS-CoV-2 variants.
• To assess the impact of these mutations on viral infectivity, receptor binding, and immune escape.
• To evaluate potential therapeutic strategies against variant S protein-mediated infection.

Main Methods:

• Assessment of spike protein proteolytic properties and receptor binding affinity.
• Utilized a vesicular stomatitis virus (VSV)-based pseudovirus system to evaluate infectivity and immune escape.
• Tested the efficacy of neutralizing monoclonal antibodies (mAbs), vaccinated sera, protease inhibitors, and endocytosis inhibitors.

Main Results:

• Significant changes in viral infectivity were observed in certain SARS-CoV-2 variants, with B.1.617.2 showing enhanced infectivity compared to D614G.
• Neutralizing mAbs and vaccinated sera demonstrated reduced efficacy against S proteins of some variants, indicating partial or complete immune escape.
• Protease inhibitors and endocytosis inhibitors effectively blocked viral infection mediated by SARS-CoV-2 variant S proteins.

Conclusions:

• SARS-CoV-2 variants exhibit altered infectivity and antigenicity, posing challenges to existing antibody-based interventions.
• The study highlights the importance of understanding viral evolution for developing effective countermeasures.
• Protease and endocytosis inhibitors represent promising therapeutic options against SARS-CoV-2 variants.