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Unique genomic features of fatal coronaviruses

SARS-CoV-2, the virus that causes COVID-19, isolated from a patient in the U.S. The spikes on the outer edge of the virus particles give coronaviruses their name, which means crown-like. NIAID Rocky Mountain Laboratories

Coronaviruses are a large family of viruses that mostly cause respiratory illness. There are thousands of coronaviruses. They usually circulate among animals such as pigs, camels, bats, and cats. But sometimes these viruses can make the jump to humans and cause disease.

Seven coronaviruses are known to sicken people. Four of these cause only mild to moderate disease. Three coronaviruses have emerged during the past 20 years that can cause serious illness or death.

The first caused the outbreak of Severe Acute Respiratory Syndrome (SARS) in November 2002. The virus (SARS-CoV) was contained, and no cases have been reported since 2004. Middle East Respiratory Syndrome (MERS) was identified in September 2012. There are still small outbreaks of this coronavirus (MERS-CoV) today. SARS has an estimated fatality rate of 9% and MERS of 36%.

The current global pandemic, caused by the coronavirus SARS-CoV-2, emerged in December 2019. Coronavirus disease 19 (COVID-19) has resulted in an estimated 470,000 deaths worldwide to date.  Researchers are trying to uncover why the coronaviruses responsible for COVID-19, MERS, and SARS cause more severe illness than other coronaviruses.

A team led by Drs. Noam Auslander, Ayal Gussow, and Eugene Konnin of NIH’s National Library of Medicine (NLM) set out to identify features of the viruses’ genomes that can make them deadly. In addition to NLM, the study was also supported by NIH’s National Institute of Mental Health (NIMH) and National Heart, Lung, and Blood Institute (NHLBI). The findings appeared on June 10, 2020, in Proceedings of the National Academy of Sciences.

The researchers analyzed the complete genomes of all human coronaviruses as well as closely related animal ones. They aligned the genomes to identify regions where the genetic sequences differed. Using machine learning, they investigated these differences and their potential effects.

The team was able to identify protein features unique to the COVID-19, MERS, and SARS coronaviruses. These features are linked to their high fatality rate as well as their ability to move from animal to human hosts.

In the three fatal coronaviruses, the researchers found insertions of specific stretches of amino acids in two coronavirus proteins—the spike protein on the surface of the virus and the central nucleocapsid protein, which holds the viral genome. These insertions aren’t found in the four non-lethal human coronaviruses. However, they are found in other closely related coronaviruses that infect animals, such as bats.

The insertions in the spike protein appear to help the viruses penetrate human cells. The researchers determined that the spike insertions may improve the viruses’ ability to interact with the receptor on human cells that the viruses use to gain entry. The role of the insertions in the nucleocapsid protein are unclear, as this protein has several functions.

Laboratory experiments will be needed to further explore the role of these insertions. Nevertheless, the findings could help prevent a future deadly coronavirus outbreak.

“This innovative research is critical to improve researchers’ understanding of SARS-CoV-2 and aid in the response to COVID-19,” says NLM Director Dr. Patricia Flatley Brennan. “Predictions made through this analysis can inform possible targets for diagnostics and interventions.”