Researchers found evidence indicating that the virus has—under selection pressure—made itself more stable, giving it a “significant boost in infectivity”

While the COVID-19 pandemic continues to spread across the United States and throughout the world, new research suggests that a coming genetic mutation within the SARS-CoV-2 coronavirus may make it much more dangerous than it already is. This finding has significant implications for clinical laboratories that perform COVID-19 testing and the in vitro diagnostics (IVD) companies that develop and manufacture tests for COVID-19.

The mutation, called D614G, will provide the coronavirus with sturdier spikes that will increase its ability to latch onto and infect cells. That’s according to a study conducted at The Scripps Research Institute (Scripps) in Jupiter, Fla., which found that a mutated coronavirus may be up to 10 times more infectious than the original strain.

“Viruses with this mutation were much more infectious than those without the mutation in the cell culture system we used,” said Hyeryun Choe, PhD, Professor, Department of Immunology and Microbiology, Scripps Research, and senior author of the study, in a Scripps news release.

Choe and Michael Farzan, PhD, co-chair and professor in the Department of Immunology at Scripps Research, co-authored the study, titled, “The D614G Mutation in the SARS-Cov-2 Spike Protein Reduces S1 Shedding and Increases Infectivity.” Their work is currently under peer review and can be downloaded on bioRxiv.

A More Flexible and Potent Coronavirus May Be Coming

The researchers found that coronavirus particles containing the mutation tend to have four to five times more functional spikes than particles without the mutation. The spikes enable the virus to bind to cells more easily. The research suggests that the greater the number of functional spikes on the viral surface the greater the flexibility and potency of the coronavirus.

In the Scripps news release, Farzan said, “more flexible spikes allow newly made viral particles to navigate the journey from producer cell to target cell fully intact, with less tendency to fall apart prematurely.

“Over time, it has figured out how to hold on better and not fall apart until it needs to,” he added. “The virus has, under selection pressure, made itself more stable.”

The image above, taken from the Scripps Research news release, shows “a cryogenic electron microscope image of a SARS-CoV-2 spike protein side view, the S1 section of the spike is shown in green and the S2 portion is shown in purple. This unique two-piece system has shown itself to be relatively unstable. A new mutation has appeared in the viral variant most common in New York and Italy that makes this spike both more stable and better able to infect cells.” (Graphic and caption copyright: Andrew Ward lab, Scripps Research.)

Mutation Makes SARS-CoV-2 Coronavirus ‘Much More Stable’

The two Scripps scientists have studied coronaviruses for nearly 20 years and performed extensive research on the Severe Acute Respiratory Syndrome (SARS) outbreak that occurred in 2003. They noted that there is a difference between spike proteins of SARS, an earlier strain of coronavirus, and the new SARS-CoV-2 strain. 

The protein spikes of both strains were originally tripod shaped. However, the spikes of the SARS-CoV-2 coronavirus are divided into two different segments: S1 and S2. According to the published study: “The S1domain mediates receptor binding, and the S2 mediates downstream membrane fusion.”

This feature originally produced unstable spikes, but with the D614G mutation, the tripod breaks less frequently, which makes more of the spikes fully functional and the virus more infectious.

“Our data are very clear, the virus becomes much more stable with the mutation,” Choe said in the news release.

Is COVID-19 Spread Due to ‘Founder Effect’

The scientists also examined whether the spread of COVID-19 could have been the result of the “Founder Effect,” which is seen when a small number of variants fan out into a wide population by chance. Could the founder effect explain why COVID-19 outbreaks in some areas of the world were more severe than others? The researchers believe their data definitively answered that question. 

“There have been at least a dozen scientific papers talking about the predominance of this mutation,” Farzan said. “Are we just seeing a founder effect? Our data nails it. It is not the founder effect.”

Hyeryun Choe, PhD (left), and Michael Farzan, PhD (right), scientists at Scripps Research explained that their research was performed using engineered viruses and that their observations of the virus and its mutation may not translate to increased transmissibility when a virus attaches to a host outside the lab. COVID-19 and its mutation appear to be relatively stable and are mutating at a rate slower than that of the seasonal flu, which may be critical factors in the development of a vaccine. (Photos copyright: Scripps Research.)

Findings Raise ‘Interesting’ Questions about the COVID-19 Coronavirus

Nevertheless, the two scientists are curious about some of their findings. “Our data raise interesting questions about the natural history of SARS-CoV-2 as it moved presumably from horseshoe bats to humans. At some point in this process, the virus acquired a furin-cleavage site, allowing its S1/S2 boundary to be cleaved in virus-producing cells. In contrast, the S1/S2 boundary of SARS-CoV-1, and indeed all SARS-like viruses isolated from bats, lack this polybasic site and are cleaved by TMPRSS2 or endosomal cathepsins in the target cells.

“In summary, we show that an S protein mutation that results in more transmissible SARS-CoV-2 also limits shedding of the S1 domain and increases S-protein incorporation into the virion. Further studies will be necessary to determine the impact of this change on the nature and severity of COVID-19,” the Scripps researchers concluded.

However, not all Scripps researchers agreed with the conclusions of Choe and Farzan’s research.

The Times of Israel reported that Kristian Andersen, PhD, a professor in the Department of Immunology and Microbiology, Scripps California Campus, told the New York Times that “other analyses of virus variants in labs had not found significant differences in infection rates.”

“That’s the main reason that I’m so hesitant at the moment,” Andersen said. “Because if one really was able to spread significantly better than the other, then we would expect to see a difference here, and we don’t.”

Times of Israel also reported that “In late May researchers in University College London said their studies of the genomes of more than 15,000 samples had not shown one strain being more infectious than others.”

So, the jury’s out. Nonetheless, clinical laboratory leaders will want to remain vigilant. A sudden increase in COVID-19 infection rates will put severe strain on already strained laboratory supply chains.

—JP Schlingman

Related Information:

Study: Dominant Form of Virus ‘10 times’ More Infectious than Original Strain

Mutated Coronavirus Shows Significant Boost in Infectivity

The D614G Mutation in the SARS-CoV-2 Spike Protein Reduces S1 Shedding and Increases Infectivity