It’s well-known that the virus that causes COVID-19 gets into human cells by taking advantage of a protein called ACE2. But SARS-CoV-2 is a versatile virus, and we’re still working to understand it. Like, recent research suggests there’s at least one more protein it might use to get into cells. If true, that might help us understand how this virus is causing some of its stranger symptoms. And, most importantly, it might lead us towards new ways to help people infected with it.
• ACE2 is a cellular receptor— a protein that juts out of cell membranes and binds to other molecules. Receptors in general are a super important part of how cells interact with their environments.
• But if a virus can bind to one of them, it can often use the receptor to attach to the cell’s membrane and get inside— kind of like grabbing a doorknob lets you open a door. And there seems to be growing evidence that this new coronavirus can grab at least two different doorknobs.
• One we haven’t talked about yet is called “cluster of differentiation 147”, or CD147 for short. Actually, it has lots of names: EMMPRIN, M6, Basigin … but they’re all the same basic protein. One of CD147’s most common jobs is facilitating communication between cells as they coordinate tasks.
• So, it’s found on a bunch of different kinds of cells all over the body, and it has its molecular hands in lots of physiological pots, so to speak. Now, there are a number of viruses that use CD147 to infect cells, including HIV and measles.
• The original SARS virus seemed to have this ability, too. And, a study put online in March 2020 suggests that SARS-CoV-2 is following in its footsteps. In that study, researchers found that CD147can binds to the virus’s spike proteins— those, well, spikey proteins on the outside of coronaviruses.
• They’re the part that binds to ACE2, so that makes sense. And though the study isn’t peer-reviewed yet, virologists seem to be taking the results and their implications seriously. If SARS-CoV-2 is using CD147 as an alternate route into cells, that might help us understand some of the peculiar traits of COVID-19— like its relationship with type 2 diabetes.
• See, a 2010 study found that high blood sugar increases the body’s production of CD147. So, if the virus can use this receptor to get into cells, then people with higher blood sugar may be more susceptible to infection. And people with diabetes tend to have higher blood sugar.
• That could explain the results of a paper from June, which found that people with type 2 diabetes are more likely to get severe COVID-19 symptoms. And diabetes might not be the only condition to watch out for.
• Researchers in a June paper looked to see where the known and potential receptors for this virus are in the body, and how that changes with disease. They included ACE2, CD147, and another receptor, called CD26, that some have suggested may also be used. And it turns out they’re all over the place. And CD147 in particular is more common in conditions like asthma, obesity, COPD, and hypertension.
• It may even tie into some skin rashes associated with COVID-19! Another, kind-of-odd symptom of some COVID-19 infections that might relate to CD147 is excessive blood clotting. Now, blood clots can be caused by a variety of things, including inflammation and damaged blood vessels.
• But they can also be caused by antibodies. See, if a virus attaches to red blood cells, the immune system will send antibodies to attack it. And if lots of those antibodies end up stuck on to viruses that are attached to red blood cells, they can make the cells kind of “sticky” and cause clots.
• While red blood cells don’t have ACE2 on them, they do have CD147. In fact, it’s the receptor that malaria parasites use to get inside them. So, if SARS-CoV-2 also binds to CD147, that might help explain patients’ excessive clotting. Plus, CD147 is found in endothelial cells: the cells that line the inside walls of blood vessels.
• If the receptor is helping the virus infect those cells directly, that could further explain the clotting as well as other cardiovascular effects of COVID-19, like high blood pressure.
• All of that might sound scary, but understanding how COVID-19 interacts with other health conditions is an important step in figuring out how best to treat patients. And CD147 doesn’t just help explain COVID-19’ saw full effects.
• It might also lead us towards better treatments for them. See, in that preprint paper from March, researchers also reported that a laboratory-designed antibody called Meplazumab seems to stop the SARS-CoV-2 virus from infecting cells.
• It was designed to glom onto CD147 and prevent things from binding to it. So, it may essentially take away many of the virus's doorknobs, and therefore, reduce the overall impact the infection has on the body.
• And a separate trial of 17 COVID-19 patient sin a Chinese hospital found exactly that— their conditions improved when treated with Meplazumab. That’s a super small study, of course, and it also still needs to be peer-reviewed.
• So, we should take the findings with a grain of salt. Plus, the antibody isn’t actually approved for human use yet, so we’d need to make sure it’s safe, too. Researchers have also been looking at a drug called azithromycin.
• It’s an antibiotic used against certain bacterial infections, but it’s also used to treat malaria— in part because it seems to block the parasites from using CD147 to get into blood cells. So, it might be able to block SARS-CoV-2 from infecting cells the same way.
• But we’ll need to see that happen in high-quality research before we get too excited. And, it’s entirely possible neither of these will pan out— or, more generally, that CD147 isn’t that important to the virus after all.
• This is what it looks like for scientific research to happen in real-time! We’re getting a lot of new information about this virus every day, and some of it will inevitably prove less helpful than others.
• ACE2 is a cellular receptor— a protein that juts out of cell membranes and binds to other molecules. Receptors in general are a super important part of how cells interact with their environments.
• But if a virus can bind to one of them, it can often use the receptor to attach to the cell’s membrane and get inside— kind of like grabbing a doorknob lets you open a door. And there seems to be growing evidence that this new coronavirus can grab at least two different doorknobs.
• One we haven’t talked about yet is called “cluster of differentiation 147”, or CD147 for short. Actually, it has lots of names: EMMPRIN, M6, Basigin … but they’re all the same basic protein. One of CD147’s most common jobs is facilitating communication between cells as they coordinate tasks.
• So, it’s found on a bunch of different kinds of cells all over the body, and it has its molecular hands in lots of physiological pots, so to speak. Now, there are a number of viruses that use CD147 to infect cells, including HIV and measles.
• The original SARS virus seemed to have this ability, too. And, a study put online in March 2020 suggests that SARS-CoV-2 is following in its footsteps. In that study, researchers found that CD147can binds to the virus’s spike proteins— those, well, spikey proteins on the outside of coronaviruses.
• They’re the part that binds to ACE2, so that makes sense. And though the study isn’t peer-reviewed yet, virologists seem to be taking the results and their implications seriously. If SARS-CoV-2 is using CD147 as an alternate route into cells, that might help us understand some of the peculiar traits of COVID-19— like its relationship with type 2 diabetes.
• See, a 2010 study found that high blood sugar increases the body’s production of CD147. So, if the virus can use this receptor to get into cells, then people with higher blood sugar may be more susceptible to infection. And people with diabetes tend to have higher blood sugar.
• That could explain the results of a paper from June, which found that people with type 2 diabetes are more likely to get severe COVID-19 symptoms. And diabetes might not be the only condition to watch out for.
• Researchers in a June paper looked to see where the known and potential receptors for this virus are in the body, and how that changes with disease. They included ACE2, CD147, and another receptor, called CD26, that some have suggested may also be used. And it turns out they’re all over the place. And CD147 in particular is more common in conditions like asthma, obesity, COPD, and hypertension.
• It may even tie into some skin rashes associated with COVID-19! Another, kind-of-odd symptom of some COVID-19 infections that might relate to CD147 is excessive blood clotting. Now, blood clots can be caused by a variety of things, including inflammation and damaged blood vessels.
• But they can also be caused by antibodies. See, if a virus attaches to red blood cells, the immune system will send antibodies to attack it. And if lots of those antibodies end up stuck on to viruses that are attached to red blood cells, they can make the cells kind of “sticky” and cause clots.
• While red blood cells don’t have ACE2 on them, they do have CD147. In fact, it’s the receptor that malaria parasites use to get inside them. So, if SARS-CoV-2 also binds to CD147, that might help explain patients’ excessive clotting. Plus, CD147 is found in endothelial cells: the cells that line the inside walls of blood vessels.
• If the receptor is helping the virus infect those cells directly, that could further explain the clotting as well as other cardiovascular effects of COVID-19, like high blood pressure.
• All of that might sound scary, but understanding how COVID-19 interacts with other health conditions is an important step in figuring out how best to treat patients. And CD147 doesn’t just help explain COVID-19’ saw full effects.
• It might also lead us towards better treatments for them. See, in that preprint paper from March, researchers also reported that a laboratory-designed antibody called Meplazumab seems to stop the SARS-CoV-2 virus from infecting cells.
• It was designed to glom onto CD147 and prevent things from binding to it. So, it may essentially take away many of the virus's doorknobs, and therefore, reduce the overall impact the infection has on the body.
• And a separate trial of 17 COVID-19 patient sin a Chinese hospital found exactly that— their conditions improved when treated with Meplazumab. That’s a super small study, of course, and it also still needs to be peer-reviewed.
• So, we should take the findings with a grain of salt. Plus, the antibody isn’t actually approved for human use yet, so we’d need to make sure it’s safe, too. Researchers have also been looking at a drug called azithromycin.
• It’s an antibiotic used against certain bacterial infections, but it’s also used to treat malaria— in part because it seems to block the parasites from using CD147 to get into blood cells. So, it might be able to block SARS-CoV-2 from infecting cells the same way.
• But we’ll need to see that happen in high-quality research before we get too excited. And, it’s entirely possible neither of these will pan out— or, more generally, that CD147 isn’t that important to the virus after all.
• This is what it looks like for scientific research to happen in real-time! We’re getting a lot of new information about this virus every day, and some of it will inevitably prove less helpful than others.