Engineered Antibody Helps Block SARS-CoV-2 Transmission
February 14, 2022
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Posted by admin
Researchers at UC Davis Health have engineered a novel antibody, FuG1, that can directly interfere with the cell-to-cell transmission ability of SARS-CoV-2, the virus that causes COVID-19. FuG1 targets the enzyme furin, which the virus uses for its efficient chain of infections in human cells. The approach could be added to existing SARS-CoV-2 antibody cocktails for greater function against emerging variants.
“We developed an approach that interferes with the transmission chain of SARS-CoV-2. The COVID-19 vaccines are a great lifesaver in reducing hospitalizations and severe illness. Yet, we are now learning that they may not be as effective in controlling the transmissibility of the virus,” said Jogender Tushir-Singh, senior author of the study.
Tushir-Singh is an associate professor in the Department of Medical Microbiology and Immunology and a member of the UC Davis Comprehensive Cancer Center therapeutics program. His research uses rational protein engineering to generate multi-targeting antibodies as cancer therapeutics. When the pandemic hit, he began thinking of similar strategies that might work to limit the spread of the coronavirus.
Furin, found throughout the human body, is involved in various functions of cells. It is a type of enzyme, a protease, that can break down proteins into smaller components. It does this by cutting, or cleaving, the polybasic peptide bonds within the proteins. In cleaving these bonds, furin often acts as a switch, changing an inactive protein into an active one. For example, furin cleaves the inactive proparathyroid hormone into parathyroid hormone, which regulates calcium levels in the blood. It can also cleave and activate viruses that enter human cells. Pathogens that utilize furin in their human host include HIV, influenza, dengue fever and SARS-CoV-2.
When SARS-CoV-2 infects a human cell, it is in its active state, having already “cleaved” its spike protein, a key protein that binds to ACE2 receptors to gain entry. But when the virus is being synthesized within the host cell—when it is replicating—the spike is in an inactive state. The virus needs to use the host cell’s furin to cut the spike protein into two parts, S1 and S2, which makes the spike active on the viral particles for efficient transmissibility upon release.
“The virus exploits the host’s furin to transmit from one cell to another and another. This added activation step is what makes the virus highly transmissible,” said Tanmoy Mondal, the first author for the study and a post-doctoral researcher at UC Davis Health. But inhibiting furin to limit the SARS-CoV-2 chain of infection cycle is not a straightforward mechanism. “Furin is found throughout the human body and is needed for the normal functioning of many biological processes. Stopping furin from doing its job causes high body toxicity. That is why the standard furin inhibitor drugs are not a clinically feasible option,” Tushir-Singh said.
Instead, he and his team engineered a conjugated antibody targeting the SARS-CoV-2 spike protein. The design is similar to therapeutic monoclonal (IgG) antibodies but includes an added feature—Fc-extended peptide—that specifically interferes with the host furin. The researchers named this approach FuG1.
A study evaluating the efficacy of the engineered antibody was published in Microbiology Spectrum.
Source: https://phys.org/
Categories: Uncategorized
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Tags: Antibody, cancer therapeutics, cell, COVID-19, emerging variants, enzyme furin, Fc-extended peptide, FuG1, IgC, peptide, protease, protein, SARS-CoV-2, spike protein, therapeutic monoclonal, UC Davis Health, virus
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