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Did SARS-CoV-2 Emerge From Nature or a Lab?

Did the SARS-CoV-2 virus emerge in the human population spontaneously or was it engineered in a laboratory? Several months into this pandemic, there are still many more questions than answers about this stealthy new coronavirus that has commandeered the world stage. Its ability to enter a human population for the first time and spread quickly and with such unpredictable outcomes has led to many conflicting theories and suspicions about its origins.

“People are hungry for basic information to dispel the rumors that are out there,” says Benhur Lee, MD, Professor of Microbiology and Ward-Coleman Chair in Microbiology at the Icahn School of Medicine at Mount Sinai.

In March, Jillian Carmichael, PhD, a postdoctoral fellow in Dr. Lee’s lab, created a blog to address the misinformation and confusion about the COVID-19 disease caused by the virus that she was seeing on social media. In addition, “I was getting so many questions about SARS-CoV-2 from friends and family that I couldn’t answer them all. I decided to reach out to my virology colleagues for help.”

Together with Christian Stevens, an MD/PhD student in the Lee lab, Dr. Carmichael launched a science-communications blog. Since then, they have worked with a team of graduate students and postdoctoral fellows to parse through reams of studies to create an ongoing series of posts that educate the public about what is plausible and what is not based on their knowledge of science and virology, in particular. Their posts have received traffic from more than 100 countries.

One persistent rumor they sought to demystify for the public was whether SARS-CoV-2 could have been deliberately engineered.

“While nothing is impossible in science, there are some things we do know, and it is very unlikely that SARS-CoV-2 could have been designed in a lab,” says Mr. Stevens, who helps engineer viruses in Dr. Lee’s lab. “We have a natural hypothesis that fits all the evidence so far.”

There are two ways to engineer something in biology, Mr. Stevens says. You take what you know works and piece it together so that it works in a new way. Or, you simulate the way nature does it and tweak it in order to make improvements.

“When the exact parts of the SARS-CoV-2 virus are plugged into a computer model, they look like they’re going to perform really badly,” he says. “The computer would tell you this is a terrible idea, try something better. A human would have been unlikely to rationally design this.”

In January, when the Chinese government released the virus’ genome, which showed its similarity to a virus from a horseshoe bat, researchers gained a better understanding of its makeup. They found that no prior studies existed to explain the way in which this new virus worked, and two distinct features made the theory supporting its natural evolution more likely.

First, a piece of the virus’ spike protein—called the receptor-binding domain (RBD)—provides the virus with an exceptional ability to attach to the ACE2 protein located on the outer surface of cells in various organs. Second, the backbone of the virus—its overall molecular structure—differed substantially from other coronaviruses and mostly resembled related viruses found in bats. If SARS-CoV-2 had been deliberately engineered in a laboratory it would have been constructed from a virus that was known to cause disease, and these did not.

In addition, the SARS-CoV-2 virus has features that would make it difficult to engineer in a lab. The RBD on the spike protein closely resembles that found in a coronavirus in pangolins—an animal also called a “scaly anteater” that is one of the world’s most trafficked. The theory that a bat virus mixed with, potentially, a pangolin virus, mutated, and then jumped to humans continues to make the most sense.

Then, he says, there is the virus’ biological makeup. It has a polybasic cleavage site, which appears to give it the ability to connect to many different tissue types in the human body. While additional testing is needed, early indications are that SARS-CoV-2 does hit many areas of the body in addition to the lungs. By comparison, previous coronaviruses all had monobasic cleavage sites that connected to fewer tissue types. And last, but not least, the virus has O-linked glycans, which may function to shield the virus from the immune system. This means that in order to develop, the virus probably would have needed a human immune system, something unlikely to have been engineered in cell culture.

On the flip side, says Mr. Stevens, there is plenty of evidence to support the premise that the virus emerged naturally and jumped into humans either already possessing the tools it needed to mutate and begin infecting them quickly, or acquiring these tools soon after landing in the human population.

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