Featured Discovery

Home > Featured Discovery > New Strategy Facilitating Development of Antibodies and Vaccines against SARS‐CoV‐2

New Strategy Facilitating Development of Antibodies and Vaccines against SARS‐CoV‐2

March 23, 2021      Author:

By March 15, 2021, SARS-CoV-2 has infected 120 million people and has been responsible for the death of 2.6 million people worldwide. This is the most serious global public health emergency of this century. The virus first binds to the human receptor protein angiotensin-converting enzyme (ACE2) through the receptor binding domain (RBD) on the highly glycosylated spike protein (S), and then invades human cells; therefore, the glycosylated RBD itself is also a key target for vaccines and neutralizing antibodies.

Recently, Wang Ping's research team from the School of Chemistry and Chemical Engineering, SJTU, had their latest research results published on the website of Angewandte Chemie International Edition, titled "Synthetic Homogeneous Glycoforms of the SARS-CoV-2 Spike Receptor-Binding Domain Reveals Different Binding Profiles of Monoclonal Antibodies". Wang's team combined protein chemistry, glycochemistry and protein expression technology to develop a strategy for the efficient synthesis of glycosylated S-RBD. This work provides a platform for efficient and large-scale preparation of uniform sugar chain S-RBD, which will help the development of more effective anti-coronavirus drugs and vaccines. At the same time, the synthesis platform is also helpful for the research on other coronaviruses (such as SARS, MERS).

This research was funded by the National Natural Science Foundation of China, the major research project of "Dynamic Modification of Biomacromolecules and Chemical Intervention", and the Interdisciplinary Special Fund of Shanghai Jiao Tong University. Doctoral student Ye Farong, from School of Chemistry and Chemical Engineering, SJTU, is the first author of this article, and special researcher Wang Ping is the corresponding author. This work was also strongly supported by researcher Yu Biao and Wang Jing from CAS Shanghai Institute of Organic Chemistry, and Professor Ying Tianlei from Fudan University.

 

Author: Shen Ying

                               Source: School of Chemistry and Chemical Engineering, SJTU

Translated by Fu Jing

Proofread by Xiao Yangning, Fu Yuhe

 

ABSTRACT:

SARS‐CoV‐2 attaches to its host receptor, angiotensin‐converting enzyme 2 (ACE2), via the receptor‐binding domain (RBD) of the spike protein. The RBD glycoprotein is a critical target for the development of neutralizing antibodies and vaccines against SARS‐CoV‐2. However, the high heterogeneity of RBD glycoforms may lead to an incomplete neutralization effect and impact the immunogenic integrity of RBD‐based vaccines. Investigating the role of different carbohydrate domains is of paramount importance. Unfortunately, there is no viable method for preparing RBD glycoproteins with structurally defined glycans. Herein we describe a highly efficient and scalable strategy for the preparation of six glycosylated RBDs bearing defined structure glycoforms at T323, N331 and N343. A combination of modern oligosaccharide, peptide synthesis and recombinant protein engineering provides a robust route to deciphering carbohydrate structure-function relationships.