); however, none proved effective in efficiently neutralizing the virus.
Simultaneously, various teams extracted antibodies from humans infected with SARS-CoV-2 or animals vaccinated with SARS-CoV-2 spike (S) proteins (3✔ ✔Trusted Source
Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model
Go to source
,4✔ ✔Trusted Source
Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody
Go to source
).
Neutralizing Antibodies Repurposed for Viral Therapy
“The emergence of SARS-CoV-2 stimulated interest in repurposing neutralizing antibodies against related viruses for therapeutics. Zhao et al. used a rapid, affinity-maturation strategy to generate mutations within a neutralizing monoclonal antibody against SARS-CoV-1 isolated from a convalescent donor. The engineered antibodies were displayed on the surface of yeast, and clones with increased affinity for the SARS-CoV-2 S protein were isolated and characterized. A candidate engineered antibody blocked SARS-CoV-2 infection of cells in vitro and prophylactically protected hamsters from viral challenge, highlighting the potential of this approach for antibody discovery for other viruses,” summarized the editor John F. Foley.
Advertisement
This study employs hybrid “refocusing” to engineer existing antibodies like CR3022, originally neutralizing SARS-CoV-1, for related virus targeting (1✔ ✔Trusted Source
Broadening a SARS-CoV-1-neutralizing antibody for potent SARS-CoV-2 neutralization through directed evolution
Go to source
).SARS-CoV-1 Antibody Tailored!
By utilizing synthetic antibody maturation known as synthetic antibody maturation by multiple point loop library enrichments (SAMPLER), the team enhanced CR3022, a SARS-CoV-1-neutralizing antibody isolated in 2006 from a convalescent donor (1✔ ✔Trusted Source
Broadening a SARS-CoV-1-neutralizing antibody for potent SARS-CoV-2 neutralization through directed evolution
Go to source
).
Engineered CR3022 demonstrated SARS-CoV-2 neutralization and safeguarded against infection in a small animal model. Moreover, comprehensive sequencing and crystallographic analysis unveiled how the antibody adapts to sequence variations between SARS-CoV-1 and SARS-CoV-2 during the engineering process (1✔ ✔Trusted Source
Broadening a SARS-CoV-1-neutralizing antibody for potent SARS-CoV-2 neutralization through directed evolution
Go to source).
Directed Evolution’s Promise For Viral Defence
The study demonstrated the potential of antibody refocusing to generate potent neutralizing antibodies against new viruses or variants, leveraging closely related virus nAbs (1✔ ✔Trusted Source
Broadening a SARS-CoV-1-neutralizing antibody for potent SARS-CoV-2 neutralization through directed evolution
Go to source
).
By reengineering the SARS-CoV-1 nAb CR3022, the team achieved >1000-fold stronger affinity for the receptor binding domain (RBD) of SARS-CoV-2, leading to potent SARS-CoV-2 neutralization. Also, the protective effects in a small animal model, surpassing its neutralization of SARS-CoV-1 were evidenced by the study (1✔ ✔Trusted Source
Broadening a SARS-CoV-1-neutralizing antibody for potent SARS-CoV-2 neutralization through directed evolution
Go to source).
Since affinity engineering takes under a month and doesn’t rely on donor samples or structural information, this method complements traditional antibody discovery for swift response to pandemics (1✔ ✔Trusted Source
Broadening a SARS-CoV-1-neutralizing antibody for potent SARS-CoV-2 neutralization through directed evolution
Go to source).
Thus, this workflow offers a blueprint to swiftly expand antibody neutralization across related yet resistant viruses.
References :
- Broadening a SARS-CoV-1-neutralizing antibody for potent SARS-CoV-2 neutralization through directed evolution – (https://pubmed.ncbi.nlm.nih.gov/37582161/)
- Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody – (https://pubmed.ncbi.nlm.nih.gov/32065055/)
- Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model – (https://pubmed.ncbi.nlm.nih.gov/32540903/)
- Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody – (https://pubmed.ncbi.nlm.nih.gov/32422645/)
Source: Medindia
