Study Finds That Furin Cleavage Site is Key to SARS-CoV-2 Pathogenesis but Not Essential for Transmission
Nikhil Prasad Fact checked by:Thailand Medical News Team Mar 13, 2025 6 hours, 31 minutes ago
Medical News: Since the emergence of SARS-CoV-2, scientists have been striving to understand what makes this virus so effective at infecting humans. A recent study led by researchers from the University of Texas Medical Branch and Emory University has now shed light on a crucial aspect of the virus: the furin cleavage site. This small region in the spike protein of the virus plays a major role in its ability to cause disease, or pathogenesis, but appears to be less important for transmission between individuals. This
Medical News report delves into the significance of this discovery and what it means for future research on COVID-19.
Study Finds That Furin Cleavage Site is Key to SARS-CoV-2 Pathogenesis but Not Essential
for Transmission
Understanding the Furin Cleavage Site and the Study Findings
SARS-CoV-2 differs from other related coronaviruses in having a furin cleavage site (FCS) in its spike protein. This site is a specific sequence of amino acids that allows the virus to be processed more efficiently by human cells, facilitating infection and disease severity. Scientists have long speculated that this site plays a role in both how the virus spreads and how severe an infection can become.
In this study, researchers engineered a version of the virus with a disrupted FCS while keeping the overall spike protein structure intact. They tested this modified virus in both laboratory cell cultures and animal models to observe how it behaved compared to the normal virus. The results showed that while the virus with the altered FCS was significantly weakened in its ability to cause disease, it was still capable of transmitting from one host to another.
Impact on Infection and Disease Severity
One of the most striking findings of the study was the impact on viral replication. The modified virus showed reduced replication in human respiratory cells, meaning it was less effective at infecting lung tissues. This suggests that the furin cleavage site is a key factor in how SARS-CoV-2 establishes infection in the body and causes illness. In animal models, the altered virus led to much milder symptoms compared to the normal virus. Hamsters infected with the modified virus experienced minimal weight loss and showed fewer signs of lung damage, a stark contrast to those infected with the original strain, which exhibited significant illness.
The study also examined viral antigen presence in lung tissues. The original virus showed widespread infection in lung cells, while the altered virus displayed limited presence, further confirming its weakened ability to cause severe disease. Additionally, histological analysis (microscopic examination of tissue) indicated that animals infected with the modified virus had much less inflammation and tissue damage.
Transmission of the Virus Remains Unaffected
Despite its weakened ability to cause severe illness, the modified virus was still capable of spreading from infected hamsters to healthy ones. The researchers conducted direct-contact tra
nsmission experiments, where an infected hamster was placed with a healthy one. In every case, the virus still managed to spread, indicating that an intact FCS is not strictly necessary for transmission.
However, there was a notable difference in transmission efficiency. While the modified virus could still spread, it was transmitted at lower levels compared to the original strain. This suggests that while the furin cleavage site enhances the virus's ability to replicate and cause disease, it may also contribute to how efficiently it spreads between hosts.
The Role of Furin Cleavage in Virus Evolution
The findings of this study add to a growing body of evidence that suggests SARS-CoV-2 has evolved specific mechanisms to maximize both its spread and its ability to cause disease. The furin cleavage site, which is not found in closely related coronaviruses, appears to be one of the features that gives SARS-CoV-2 its unique characteristics.
This study also raises important questions about how the virus might evolve in the future. If a version of the virus with a disrupted furin cleavage site can still spread, there is a possibility that variants with altered versions of this site could emerge. Understanding how these changes impact the virus’s ability to cause disease and spread is essential for monitoring new variants and developing effective countermeasures.
Conclusions and Implications for Future Research
The study’s findings provide critical insights into the function of the furin cleavage site in SARS-CoV-2. While it is not essential for transmission, it plays a crucial role in determining the severity of infection. This suggests that targeting the FCS could be a potential strategy for developing treatments that reduce disease severity without necessarily affecting the virus’s ability to spread.
From a public health perspective, these findings underline the importance of monitoring mutations in the spike protein. Since the furin cleavage site plays a major role in pathogenesis, any changes to this region in emerging variants could significantly impact the severity of COVID-19 infections.
The study also highlights the complexity of SARS-CoV-2’s evolution. While some mutations may weaken the virus’s ability to cause disease, they do not necessarily make it less transmissible. This means that even variants with reduced severity can continue to spread widely, reinforcing the need for ongoing surveillance and vaccination efforts.
The study findings were published on a preprint server and are currently being peer reviewed.
https://www.biorxiv.org/content/10.1101/2025.03.10.642264v1
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https://www.thailandmedical.news/news/covid-19-new-scientist-hypothesize-that-furin-plays-a-key-role-in-the-pathogenesis-of-covid-19-associated-neurological-disorders
https://www.thailandmedical.news/news/covid-19-research-scientist-discover-unique-epitope-at-sars-cov-2-spike-furin-cleavage-site-and-also-a-new-corresponding-monoclonal-antibody
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