A Nanobody Can Neutralize SARS-CoV-2 by Stabilizing Inactive Spike Protein

Posted by beauty33 on January 26th, 2021

In the past 20 years, there are three zoonotic β-coronaviruses that have entered the human population and caused severe respiratory symptoms with high mortality. Caused by SARS-CoV-2, the COVID-19 pandemic is the easiest to spread among the three coronaviruses. So far, no preventive treatment for the coronavirus has been approved, and the timetable for the effective and widely available vaccine against SARS-CoV-2 is still uncertain. Therefore, the development of new treatment and prevention methods remains crucial. 

In a new study, researchers from the University of California, San Francisco and other research institutions screened yeast surface display libraries (containing more than 2×10⁹ synthetic nanobody sequences) that bind to the S protein extracellular domain (ectodomain), and they isolated single domain antibody (Nanobody) that neutralizes SARS-CoV-2. Their relevant research results were recently published in the journal Science, with the title of the paper An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike.

The virus particles of the coronavirus are surrounded by a membrane containing the homotrimeric transmembrane glycoprotein, the spike protein (S protein), which is responsible for the virus to enter the host cell. The surface exposed part of S protein consists of two domains, S1 and S2. S1 binds to the host cell receptor angiotensin converting enzyme 2 (ACE2), while S2 catalyzes the fusion of the virus and the host cell membrane.

These authors used a mutant form of SARS-CoV-2 S protein (SpikeS2P) as an antigen, and labeled SpikeS2P with biotin or with fluorescent dyes, and through multiple rounds of screening---first through magnetic bead binding followed by fluorescence-activated cell sorting---to select yeasts displaying nanobodies. These nanobodies are divided into two categories, namely Class I and Class II nanobodies.

In the study, Class II neutralizing nanobodies potentially show a new mechanism to disrupt the function of S protein. The paired use of class I and class II nanobodies in a preventive or therapeutic cocktail could strongly neutralize and prevent the escape variant of SARS-CoV-2. Therefore, the combined stability, effectiveness, and diverse epitope binding of the anti-S protein nanobodies screened by these authors provide a unique potential prevention and treatment strategy for limiting the continued deaths caused by the COVID-19 pandemic.

About the author

Creative Diagnostics is a leading manufacturer of magnetic particles and related products for immunoassay development. It provides a comprehensive list of immunomagnetic bead products conjugated with different coating materials and functional groups in multiple sizes to meet needs for research and industrial prospect development. It has recently developed a series of SARS-CoV-2 magnetic particles for research applications in immunoprecipitation and minimum protein purification to support the entire scientific community in their efforts to fight against SARS-CoV-2 and COVID-19.

Reference

1. Schoof, M., Faust, B., Saunders, R. A., Sangwan, S., Rezelj, V., Hoppe, N., ... & Kratochvil, H. T. (2020). An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike. Science.