Nanobodies targeting SARS-CoV-2 variants

Area of Science:

• Virology
• Immunology
• Biotechnology

Background:

• Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused the COVID-19 pandemic, with its surface spike (S) protein crucial for viral entry.
• The S protein's receptor-binding domain (RBD) is a key target, but frequent mutations, like those in Omicron, reduce therapeutic antibody effectiveness.
• Nanobodies, small high-affinity antibodies, offer advantages in targeting viral proteins, including those on variants.

Purpose of the Study:

• To review the main protein constituents of SARS-CoV-2 and their functions.
• To describe S protein-mediated viral entry and fusion processes.
• To comprehensively review SARS-CoV-2-targeting nanobodies, including those effective against variants and subvariants.

Main Methods:

• Review of scientific literature on SARS-CoV-2 proteins and viral entry mechanisms.
• Analysis of studies detailing nanobody development and characterization against SARS-CoV-2.
• Categorization of nanobodies based on their binding targets (RBD, non-RBD S proteins, non-S proteins) and effectiveness against different variants.

Main Results:

• The SARS-CoV-2 S protein and its RBD are critical for viral entry and are major therapeutic targets.
• SARS-CoV-2 variants, particularly Omicron, exhibit reduced sensitivity to existing therapeutic antibodies.
• A diverse range of nanobodies targeting various SARS-CoV-2 proteins, including those on variants, have been identified.

Conclusions:

• Nanobodies demonstrate significant potential as therapeutics against SARS-CoV-2 due to their binding affinity, stability, and accessibility.
• Targeting the S protein, especially the RBD, remains a primary strategy, but nanobodies also show promise against non-RBD and non-S targets.
• Further development of nanobodies is crucial for generating potent treatments effective against current and future SARS-CoV-2 variants and subvariants.