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Updated: Jul 8, 2025
Detection of SARS-CoV-2 Neutralizing Antibodies using High-Throughput Fluorescent Imaging of Pseudovirus Infection
Published on: June 5, 2021
A potential broad-spectrum neutralizing antibody against Betacoronavirus
Rong Wang1, Jiazheng Guo1, Jiansheng Lu1
1Beijing Institute of Biotechnology, Beijing, China.
Abstract:
Three pandemics caused by human Betacoronavirus had broken out in the past two decades. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was one of the novel epidemic strains which caused the third pandemic, coronavirus disease 2019 (COVID-19), a global public health crisis. So far, more than millions of people have been infected. Considering the public health and economic impact of Betacoronavirus pandemic, drugs with broad-spectrum activity against these coronaviruses are urgently needed. In this study, two monoclonal antibodies targeting SARS-CoV-2 spike protein receptor-binding domain (RBD) with good neutralizing activity were used to construct a novel immunoglobulin-like bispecific antibody BI31. The neutralizing effect of BI31 against the pseudovirus and the authentic virus is better than that of its parent antibodies alone and in combination. What surprised us most was that the newly constructed bispecific antibody also had the neutralizing activity against SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) that the parent antibodies did not have. These suggested that the BI31 can not only be developed as a therapeutic drug against COVID-19 but it could also become a broad-spectrum therapeutic antibody against Betacoronavirus.
Insights
A new bispecific antibody, BI31, effectively neutralizes SARS-CoV-2, the virus causing COVID-19. This novel antibody also shows promise as a broad-spectrum therapeutic against Betacoronaviruses like SARS-CoV and MERS-CoV.
Area of Science:
- Virology
- Immunology
- Drug Discovery
Background:
- Three major Betacoronavirus pandemics have emerged in the last 20 years.
- Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused the COVID-19 pandemic, a significant global health crisis.
- There is an urgent need for broad-spectrum antiviral drugs targeting Betacoronaviruses due to their public health and economic impact.
Purpose of the Study:
- To construct a novel bispecific antibody, BI31, targeting the SARS-CoV-2 spike protein receptor-binding domain (RBD).
- To evaluate the neutralizing activity of BI31 against SARS-CoV-2.
- To investigate the potential of BI31 as a broad-spectrum therapeutic agent against Betacoronaviruses.
Main Methods:
- Two neutralizing monoclonal antibodies targeting the SARS-CoV-2 RBD were selected.
- An immunoglobulin-like bispecific antibody, BI31, was engineered by combining these parent antibodies.
- Neutralizing activity of BI31 was assessed against SARS-CoV-2 pseudoviruses and authentic viruses, as well as against SARS-CoV and MERS-CoV.
Main Results:
- BI31 demonstrated superior neutralizing efficacy against SARS-CoV-2 compared to its individual parent antibodies or their combination.
- BI31 exhibited significant neutralizing activity against SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), which the parent antibodies lacked.
- The bispecific antibody design enhanced the overall neutralizing potency and broadened the spectrum of activity.
Conclusions:
- BI31 is a potent neutralizing antibody against SARS-CoV-2.
- BI31 shows potential as a broad-spectrum therapeutic antibody for Betacoronavirus infections, including COVID-19, SARS, and MERS.
- The development of bispecific antibodies offers a promising strategy for combating emerging viral threats.
