How the coronavirus infects so many different parts of the body
Hello-
How have you been? I’m sending an additional mid-week newsletter to share a breaking scientific discovery that explain somethings that has been a puzzle since the start of the pandemic—
How does SARS-CoV-2 infect so many different cells in different parts of the body?
This work just came out a few hours ago in two landmark papers that were published in Science. Two groups independently show that the spike of SARS-CoV-2 uses a protein called neuropilin-1 on the surface of human cells to facilitate infection.
Why is this important?
First, because it is another piece of the puzzle in how a respiratory virus can infect tissues and organs in different parts of the body, such as the heart and the brain.
We’ve known for a while now that the virus uses its spike to get access to the cell through the ACE2 receptor. The first step is attachment of the spike. And the second is two-step cutting process (using two cleaver-like enzymes) which prepares the virus to enter the cell.
The two-step process explains why SARS-CoV-2 is better at infecting cells than its forerunner, SARS coronavirus (which had a one-step process). But it didn’t fully explain how the virus accessed cells throughout the body that don’t have many ACE2 receptors.
We've also known for months that the infectiousness of SARS-CoV-2 can't be explained simply by the enhanced presence of the receptor the virus uses to get inside the cell (ACE2). There are other "weaker" interactions that the virus uses too. Now we know that neuropilin-1 plays a major role in one of these interactions.
Second, this work opens up a new line of discovery for drugs that can slow down or even stop infection by blocking the interaction between the viral spike protein and neuropilin-1. An anti-viral treatment, that reduces the ability of the virus to infect human cells may be possible.
What is the practical significance?
One example is that we now have a plausible reason for the loss of smell due to SARS-CoV-2 infection. Somewhere between one-third to two-third of people infected with SARS-CoV-2 report disturbances in smell. But ACE2 receptors are detected at very low levels in olfactory cells involved in smell. Scientists were puzzled and there was no consensus on how actually the virus interferes with smell. Now, one of the studies has shown that the genes for neuropilin-1 are highly expressed in olfactory cells making infection of those cells the likely cause.
I’ve written in the past about what makes SARS-CoV-2 so infectious (and a manuscript that I thought I was done with will need revision in light of these significant discoveries). This newly discovered interaction does not affect attachment of the virus to the cell surface, but it significantly promotes entry and infection. What this shows is that even in cells that don’t have many ACE2 receptors the virus has found a way to get inside.
References:
Neuropilin-1 is a host factor for SARS-CoV-2 infection. Science 20 Oct 2020:
DOI: 10.1126/science.abd3072Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity Science 20 Oct 2020: DOI: 10.1126/science.abd2985
The link for the hardcover “COVID-19: Separating Fact from Fiction” is now available on Amazon’s Indian site.
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