New insights are bolstering scientists' efforts to stay ahead of COVID-19 and the next pandemic. Unexpected new discoveries about how COVID-19 infects cells could reveal the virus's ability to jump from one species to another and help scientists predict its evolution more accurately.
New research shows that COVID-19 can use alternative infection methods to infect cells without the ACE2 protein, a finding that highlights the virus's ability to adapt and infect multiple species. This variability underscores the need for continued surveillance and research to understand and reduce the potential risks posed by the virus and its variants.
The pandemic has sparked widespread debate about the mechanism by which COVID-19 invades cells, with much of the debate focusing on COVID-19's utilization of a human cell protein called ACE2. However, new research from the University of Virginia School of Medicine shows that ACE2 is not required for infection. Conversely, viruses can also use other means to infect cells.
This versatility suggests that coronaviruses can use multiple "gates" to enter cells, which may explain why coronaviruses are so good at infecting different species.
"The virus that causes COVID-19 uses ACE2 as a front door to infect cells, but we found that if the front door is blocked, it can also use a back door or a window," said Peter Kasson, MD, a researcher in the Department of Molecular Physiology and the Department of Biomedical Engineering at the University of Virginia. "This means that the virus can continue to spread as it infects new species until it adapts to using the species-specific front door. So we have to be careful about new viruses infecting us in the same way."
COVID-19 has killed nearly 7 million people worldwide. Thankfully, as vaccines become more widely available and population immunity improves, this virus is no longer a threat to most people (but it is still a problem for immunocompromised people and the elderly). As the official U.S. public health emergency expires in May, most Americans have largely returned to life similar to what it was before the pandemic emerged in 2019. But COVID-19 continues to evolve and change, and scientists are watching its movements closely so they can act quickly if more dangerous variants emerge. They are also continuing to monitor other coronaviruses in case they jump to humans and become the next big public health threat.
As part of this work, Carson and his team hope to better understand how SARS-CoV-2, the virus that causes COVID-19, enters human cells. Scientists already knew that viruses essentially knock on cells' doors by binding to the ACE2 protein. These proteins are found in large amounts on the surfaces of cells lining the nose and lungs.
However, SARS-CoV-2 can also bind to other proteins. Scientists wondered, could it be possible that SARS-CoV-2 uses these other proteins to infiltrate cells? The answer is yes. ACE-2 is the most effective way, but it is not the only way. This suggests that the virus can bind to and infect cells even if they don't have ACE-2 receptors.
Carson said the unexpected discovery may help explain why coronaviruses are so good at species jumping. He noted that this makes it even more important for scientists to pay close attention to the coronavirus. He said: "As far as we know, coronaviruses such as SARS-CoV-2 have caused one pandemic and several near misses. This shows that there are more coronaviruses out there, and we need to understand how they spread and what to pay attention to."