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Xinhua Hospital Identifies Neutralizing Antibody Against COVID-19

June 01, 2021      Author:

The new type of coronavirus pneumonia is caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV2). The virus looks like a sphere full of small "cauliflowers", which are highly penetrative spike proteins, like a key that can accurately find the "keyhole" in the cell and then allow the virus to make people sick by entering the cell, releasing genetic information, and replicating in a very short period of time. The effective neutralizing antibody can "paint" a thick "membrane" on the key's tooth mark, which blocks the keyhole and prevents the virus from entering the cell.

This research idea originated from when the COVID-19 epidemic broke out last year. Sun Kun, a pediatric expert, and Huang Lisu, the director of the infection department of Xinhua Hospital, immediately spotted the issue of child protection and set the research direction in neutralizing antibodies. Later, the joint research team identified 10 neutralizing antibodies from tens of thousands of antibodies from the serum of COVID-19 convalescent patients, and finally selected the COVID-19-specific neutralizing antibody P4A1-2A. To put it into artificial synthesis and development, the joint research team needed to give a detailed "profile" of this neutralizing antibody.

In the following preclinical trials, the antibody showed many advantages such as high efficiency, high affinity, broad spectrum, and long duration. At present, the neutralizing antibody is undergoing drug clinical trials.

 

Author: Xinhua Hospital Affiliated to SJTU School of Medicine, Kankan News

Source: WeChat account of SJTU School of Medicine

Translated by Fu Jing

Proof by Xiao Yangning, Fu Yuhe

 

ABSTRACT:

COVID-19 pandemic caused by SARS-CoV-2 constitutes a global public health crisis with enormous economic consequences. Monoclonal antibodies against SARS-CoV-2 can provide an important treatment option to fight COVID-19, especially for the most vulnerable populations. In this work, potent antibodies binding to SARS-CoV-2 Spike protein were identified from COVID-19 convalescent patients. Among them, P4A1 interacts directly with and covers majority of the Receptor Binding Motif of the Spike Receptor-Binding Domain, shown by high-resolution complex structure analysis. We further demonstrate the binding and neutralizing activities of P4A1 against wild type and mutant Spike proteins or pseudoviruses. P4A1 was subsequently engineered to reduce the potential risk for Antibody-Dependent Enhancement of infection and to extend its half-life. The engineered antibody exhibits an optimized pharmacokinetic and safety profile, and it results in complete viral clearance in a rhesus monkey model of COVID-19 following a single injection. These data suggest its potential against SARS-CoV-2 related diseases.