Novel coronavirus structure reveals targets for treatments

72

In late 2019, the first reports of an unknown respiratory infection—in some cases fatal—emerged from Wuhan, China. The source of that infection was quickly identified as a novel coronavirus, related to those that had caused outbreaks of Severe Acute Respiratory Syndrome (SARS) from 2002-2004 and Middle East Respiratory Syndrome (MERS) in 2012.

The World Health Organization declared the illness resulting from the new virus, COVID-19, a Public Health Emergency of International Concern. By early March 2020, the novel coronavirus—now named SARS-CoV-2—had infected more than 90,000 people worldwide and killed at least 3,100.

Like other coronaviruses, SARS-CoV-2 particles are spherical and have proteins called spikes protruding from their surface.

These spikes latch onto human cells, then undergo a structural change that allows the viral membrane to fuse with the cell membrane.

The viral genes can then enter the host cell to be copied, producing more viruses. Recent work shows that, like the virus that caused the 2002 SARS outbreak, SARS-CoV-2 spikes bind to receptors on the human cell surface called angiotensin-converting enzyme 2 (ACE2).

To help support rapid research advances, the genome sequence of the new coronavirus was released to the public by scientists in China.

A collaborative team including scientists from Dr. Jason McLellan’s lab at the University of Texas at Austin and the NIAID Vaccine Research Center (VRC) isolated a piece of the genome predicted to encode for its spike protein based on sequences of related coronaviruses. The team then used cultured cells to produce large quantities of the protein for analysis.

The researchers used a technique called cryo-electron microscopy to take detailed pictures of the structure of the spike protein.

This involves freezing virus particles and firing a stream of high-energy electrons through the sample to create tens of thousands of images.

These images are then combined to yield a detailed 3D view of the virus.

The researchers found that the SARS-CoV-2 spike was 10 to 20 times more likely to bind ACE2 on human cells than the spike from the SARS virus from 2002.

This may enable SARS-CoV-2 to spread more easily from person to person than the earlier virus.