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The Origins of SARS-CoV-2: Parts 1-3

Part 1: A story of bats and pangolins

Naturally, one of the first questions we ask ourselves when a new disease appears is “where did this come from?” In this post, Prof. Benhur Lee, Ward-Coleman Chair in Microbiology at Icahn School of Medicine at Mount Sinai (NYC), and his team detail the origins of SARS-CoV-2 and how it likely emerged in the human population. Specifically, they discussed two leading hypotheses for the origins of SARS-CoV-2.

Most of the viral genome likely comes from a coronavirus closely related to a horseshoe bat coronavirus called Bat CoV RaTG13.
The all-important receptor-binding domain (RBD) of the Spike protein is closely related to an entirely different coronavirus found in Malayan pangolins.

They also addressed an important result from this likely recombination event: the new RBD for SARS-CoV-2 is ten times better than SARS-CoV. As a reminder, the RBD, in part, dictates how well the spike protein gets SARS-CoV-2 into our cells by binding a human protein on cell surfaces called ACE2. The new RBD shows a 10x increase in its binding affinity for ACE2.

Transmission electron micrograph of SARS-CoV-2 virus particles, isolated from a patient. Image captured and color-enhanced at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

Part 2: A new set of tools

In Part 2, the Benhur Lee lab explores what makes SARS-CoV-2 different from other coronaviruses and why it’s so good at infecting humans. They focus on three components of the SARS-CoV-2 spike protein:

Its spike protein is very good at binding human ACE2 to enter our cells (discussed in Part I)
The spike protein can be activated in a wide range of cells and tissues (polybasic cleavage site)
The spike protein may be better at hiding from antibodies (glycan shield

The YouTube video starts with a top-down view of the SARS-CoV-2 spike protein, then spins around the side, ending back at the top. Something important about this protein is that it functions in a trimer. This means that three identical copies of the protein (light grey, dark grey, and blue, in the video) come together to perform the protein’s function. As you watch it rotate, you might notice that something looks slightly off about the blue monomer. It has a little piece that is flipped up at the top of the protein. In fact, this is the RBD getting ready to bind to human ACE2.

Part 3: Was this virus designed in lab? Accidentally released?

In Part 3, they provide current data that SARS-CoV-2 evolved naturally and highlights the point that any virus origins scenario involving a laboratory is deeply unlikely.

While this disease was not designed in a lab, this does not take humans off the hook for this pandemic. It is not intermediate horseshoe bats and Malayan pangolins that shoulder the responsibility for pandemics. The rise of zoonotic emerging diseases is due to humans encroaching on animals, not the other way around. Risks to people decrease dramatically by protecting wildlife from trafficking and limiting encroachment into wild habitats. Putting resources towards surveillance and working to better understand questions such as ‘why are bats less affected by many viruses’ could provide us the tools we need to fight future outbreaks.

We may find that turning a critical eye towards our own interactions with the environment is a more useful conversation to have about the origins of SARS-CoV-2 instead of amplifying conspiracy theories about shadowy actors. We may even find policy solutions that reduce the chances of a future pandemic by learning lessons from this one.