What Makes The Novel Coronavirus So Contagious?

Prion-like features may contribute to the transmissibility of COVID-19

Ben Callif
Apr 9, 2020 · 11 min read

Summary

The novel coronavirus that causes COVID-19, SARS-CoV-2, is significantly more contagious than the seasonal flu, and a preprint from the Human Microbiology Institute of New York may explain why. In this unpublished study, the authors examined the proteomic structure of the SARS-CoV-2 virus with computer modeling. They discovered that, unlike other closely related coronaviruses, SARS-CoV-2 contains prion-like domains in its receptor-binding spike proteins. These prion-like domains may contribute to a nearly 20-fold increase in affinity for the protein receptor found in human cells, ACE2. This unique structural element may contribute to the human-to-human communicability of COVID-19. So what are prions and why does it matter? Let’s start from the beginning.

How Coronaviruses Get Into Our Cells

At this point, we all know about the novel coronavirus causing the COVID-19 pandemic. The name “coronavirus” comes from the Latin word for crown or wreath, which refers to the visible structure of the viral particles in a cross-sectional microscopy image. But this two-dimensional description conceals the real shape of the viral particles — they’re more like spiky spheres than crowns or wreaths.

An electron micrograph of bronchitis viral particles. Image Credit: Wikimedia Commons
An artist’s rendition of a coronavirus. Image Credit: Nature
The first step of viral replication for coronaviruses. This requires the spike proteins on the virus to bind with a protein receptor on a human cell. Once the virus is securely attached the receptor and viral particle undergo endocytosis, a process through which the cell internalizes the receptor, virus, and surrounding membrane. Once inside the cell, the virus releases its RNA into the intracellular space where it can hijack the native replication machinery. Image Credits: The New York Times
Coronaviruses perform a dangerous evolutionary balancing act between deadliness and contagiousness. Image Credit: RACGP
Image Credit: Business Insider

What Makes The Novel Coronavirus Unique

As PubMed says, “COVID-19 is an emerging, rapidly evolving situation.” The research being done is of such importance that the traditional peer-review process is being expedited or even bypassed. Therefore, all of what I’m about to say is speculative to some degree. Given that disclaimer, I’m fascinated by the results of an unpublished preprint about the function of the novel coronavirus’ spike proteins.

The four orders of protein folding structure. Image Credit: Khan Academy
  1. Secondary structure: Based on the charges of the constituent amino acids, the primary structure bends and twists into three-dimensional patterns.
  2. Tertiary structure: The 3D secondary structures interact with each other to create a more complex form, known as a folded polypeptide.
  3. Quaternary structure: Once tertiary structures form, folded polypeptides can interact with each other to create complexes — large, functional, multi-unit molecules that we colloquially call proteins.
A single point mutation of the hemoglobin protein primary structure causes misfolding to occur at the level of the quaternary structure. This change causes red blood cells to become deformed, which leads to the disease known as sickle cell anemia. Image Credit: BioNinja
Many proteins have a rigid structure that determines their function, but intrinsically disordered proteins (or regions) can dynamically change shape, a feature that provides added flexibility for interaction. Image Credit: Quanta Magazine
Image Credit: Instructables

Why Prions (And COVID-19) Go Viral

As we saw with hemoglobin in the example of sickle cell anemia, a misfolded protein can be very damaging to physiological function. For this reason, cells have robust systems to ensure that newly translated proteins get folded correctly. And misfolded proteins that manage to evade those systems are swiftly degraded. But, sometimes, proteins will misfold in a very particular way that creates insoluble aggregates — clumps of dysfunctional proteins that cannot be broken down.

A misfolded prion protein (red) propagating its conformation to a normally folded protein (blue). This infectious pattern can create cascades of protein misfolding, leading to deadly aggregates. Image Credit: PLOS Pathogens
Viruses and misfolded protein aggregation are intricately linked, as is evidenced by a possible role of viral infection in Alzheimer’s disease. Image Credit: Medical Xpress
Image Credit: Cells At Work

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