As the world continues to grapple with the aftermath of the COVID-19 pandemic, the scientific community is focusing on understanding what makes certain viruses more likely to cause pandemics. Recent research on two bat coronaviruses, which are closely related to SARS-CoV-2, provides valuable insights into the factors that shape a virus’s pandemic potential. Although these bat viruses are genetically similar to SARS-CoV-2, they appear to transmit poorly in humans. This discovery sheds light on why some viruses are more likely to cause global outbreaks, offering crucial information for future pandemic preparedness.
SARS-CoV-2, the virus responsible for COVID-19, has a close genetic relationship with certain bat coronaviruses. Researchers from Yale University discovered two such viruses in bats from Laos, which share 97% of their genetic material with SARS-CoV-2. Given this high degree of similarity, it was initially assumed that these viruses might behave in a similar way to SARS-CoV-2, particularly in their ability to infect humans and cause disease.
However, the study, published in Nature Microbiology, revealed a different story. Despite their genetic resemblance to SARS-CoV-2, these bat coronaviruses did not transmit efficiently between animals and caused only mild disease in mice. This finding underscores that genetic similarity alone does not determine a virus’s pandemic potential. It suggests that other factors, such as a virus’s ability to infect certain types of cells or evade the human immune system, play a critical role in determining whether it can spread widely and cause severe illness.
For a virus to trigger a pandemic, it must successfully transmit between humans, infect human cells, evade the body’s immune defenses, and cause significant disease. SARS-CoV-2 has demonstrated a remarkable ability to do all these things, making it a formidable pandemic pathogen. But the question remains: why is SARS-CoV-2 so effective, and what makes other viruses less so?
The study’s lead author, Mario Peña-Hernández, a Ph.D. student at Yale, and his colleagues explored the differences between SARS-CoV-2 and its bat relatives. They discovered that while these bat viruses could enter some human cells and evade certain immune responses, they did not replicate well in cells from the human nose, where much of the virus transmission likely occurs. This could be a key reason why these bat viruses failed to spread effectively in the animal models used in the study.
One of the significant differences between SARS-CoV-2 and its bat relatives is the presence of a molecular feature known as the “furin cleavage site.” This site allows the spike protein of SARS-CoV-2 to be cut by an enzyme called furin, facilitating the virus’s entry into human cells. Previous studies have shown that viruses lacking this site are less transmissible and cause less severe disease.
In the recent study, the researchers found that when SARS-CoV-2 was genetically modified to lack the furin cleavage site, it behaved more like the bat coronaviruses, replicating poorly in nasal cells and transmitting less efficiently. This suggests that the furin cleavage site is a crucial factor in the pandemic potential of SARS-CoV-2. However, it is likely not the only factor. Other viral features, such as how well a virus replicates in different types of human cells, may also contribute to its ability to spread and cause disease.
The findings from this study have significant implications for how we assess the pandemic potential of emerging viruses. The fact that these bat coronaviruses did not replicate well in human nasal cells and lacked a furin cleavage site suggests that they pose a lower risk of causing a pandemic than SARS-CoV-2. However, the researchers caution that small genetic changes in these or similar viruses could enhance their ability to transmit between humans and cause more severe disease.
One critical aspect of pandemic preparedness is the ability to identify and respond to potential threats before they become widespread. By understanding the key factors that contribute to a virus’s pandemic potential, such as the presence of a furin cleavage site and the ability to replicate in nasal cells, researchers can better identify which viruses pose the greatest risk. This knowledge can then inform the development of vaccines, antiviral therapies, and other strategies to prevent future pandemics.
Another important finding from the study is that adaptive immunity against SARS-CoV-2 may offer some protection against these bat coronaviruses. Blood samples from individuals who had been vaccinated against or previously infected with SARS-CoV-2 were able to neutralize the bat viruses in laboratory tests. This suggests that existing immunity could help mitigate the impact of a new coronavirus, even if it were to emerge and start spreading among humans.
However, the researchers emphasize the importance of continuing to monitor and study these viruses. If a virus distinct enough from SARS-CoV-2 were to emerge, it could evade existing immunity, necessitating the development of new vaccines and treatments. The ability to quickly identify such a virus and understand its transmission potential would be critical in mounting an effective response.
Conclusion
Understanding what shapes a virus’s pandemic potential is crucial for preventing future global outbreaks. The study of SARS-CoV-2’s bat relatives provides valuable insights into the factors that contribute to a virus’s ability to spread and cause disease. While genetic similarity to known pandemic viruses is a useful starting point, it is not sufficient to predict a virus’s pandemic potential. Features like the presence of a furin cleavage site and the ability to replicate in nasal cells are critical indicators that must be considered.
As the world prepares for the next potential pandemic, these findings highlight the importance of continued research into emerging viruses and the development of strategies to identify and neutralize threats before they can cause widespread harm. By staying vigilant and informed, we can better protect ourselves from the next global health crisis.
