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Infectious disease

Covid-19

What we do and don't know about the novel coronavirus

Scientists race to characterize, build vaccines and treatments for the virus as thousands fall ill

by Megha Satyanarayana
January 31, 2020

 

The SARS-CoV-2 virus’s spiky surface resembles that of other coronaviruses.
Credit: NIAID-RML
The SARS-CoV-2 virus’s spiky surface resembles that of other coronaviruses.

A novel coronavirus originating in Wuhan City, China has sickened tens of thousands of people and killed more than 2,000 since scientists first discovered it in December. The virus has spread to 24 countries outside of China. On Jan. 30, the World Health Organization (WHO) declared the outbreak a public health emergency of international concern in hopes of helping nations stop the spread of the virus.

As research teams worldwide race to characterize the virus, called 2019-nCoV, governments have taken drastic action to contain its spread. The residents of Wuhan City have been quarantined. Airlines have canceled some flights in and out of China, and several countries, including the US, have imposed an isolation period for anyone returning from the affected region.

Here is what we know—and don’t know—about 2019-nCoV.

What is the latest on the outbreak?

Feb. 19, 2020:

Scientists have reported the structure of the spike protein of SARS-CoV-2. The virus uses this protein to get into and infect human cells by binding to receptors on the cell surface. The structure should help researchers develop vaccines against the virus.

Feb. 18, 2020

On Monday, the WHO started to include infections diagnosed clinically, such as by chest scans, in its numbers of confirmed cases of infections. Previously, the organization just included cases confirmed by laboratory tests for the presence of the virus in a patient. That change in counting brought the number of confirmed cases from 51,857 in its Feb. 16 situation report to 71,429 in its Feb. 17 report.

Feb. 13, 2020:

The National Institute of Allergy and Infectious Diseases (NIAID) has released transmission electron micrographs of the SARS-CoV-2 virus (see above). As expected, the virus resembles other coronaviruses, like the ones that caused severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). A NIAID blog post describes the characteristic coronavirus shape: “The spikes on the surface of coronaviruses give this virus family its name—corona, which is Latin for ‘crown,’ and most any coronavirus will have a crown-like appearance.”

China has started to report cases of infections based on new criteria, possibly including people who have minor disease symptoms. That change led to a report of more than 14,000 new cases overnight. The WHO has continued to report just cases of infections that have been confirmed by laboratory tests. The organization’s latest situation report includes 1,820 new cases in China.

Feb. 12, 2020:

The International Committee on Taxonomy of Viruses has officially named the novel coronavirus “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2). The temporary name for the virus was 2019-nCoV. The committee’s Coronavirus Study Group made the decision based on the similarities between this virus and other SARS coronaviruses, including the one that caused an outbreak in 2003.

Feb. 11, 2020:

The WHO has named the disease caused by 2019-nCoV, coronavirus disease 2019 (COVID-19).

Feb. 7, 2020:

At a press briefing, a WHO official said that the market for personal protective equipment (PPE), like masks, has been disrupted by a 100-fold jump in demand. Prices for PPE have increased up to 20-fold. As a result of increased demand, global stocks of PPE are now insufficient for WHO’s needs. The official said that inappropriate use of PPE outside of caring for patients has made the problem worse.

Researchers at South China Agricultural University announced that they think pangolins, an armored anteater-like mammal, is the animal that spread 2019-nCoV to people. Other scientists had already proposed that the virus originated in bats and then spread to another animal before infecting humans (see below). Pangolins, this team thinks, could be that intermediary critter. The group’s work has not yet been published.

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Feb. 6, 2020:

Two independent research groups report that they’ve used artificial intelligence algorithms to find molecules that could help fight the novel coronavirus. One group identified an existing drug that could block the virus from infecting human cells, and the other designed six novel molecules that could prevent the virus from replicating in a host.

Feb. 5, 2020:

The WHO announced a $675 million plan to help China and other nations prepare and respond to the novel coronavirus outbreak. According to a press release, the plan will cover February through April of this year and will have several goals, including helping to limit human-to-human spread of the virus, isolating and treating sick patients early, and minimizing social and economic impact.

The Bill & Melinda Gates Foundation will dedicate up to $100 million to help with the global response to the virus. The money will go toward improving detection, isolation, and treatment of the virus, including development of drugs and vaccines. These funds include $10 million that the foundation committed to the response in January.


Coronavirus infection
Coronaviruses are RNA viruses that typically enter human cells when their glycoproteins bind proteins on the cell surface. In the case of the virus that causes SARS, that human protein is angiotensin-converting enzyme 2 (ACE2). At this time, scientists think the novel coronavirus is similar enough to SARS that its entry point is likely ACE2 as well.

a graphic showing how the novel coronavirus might infect, where it came from, and how many people it has sickened or killed
Credit: Scientificanimations.com/C&EN/Shutterstock

Where did 2019-nCoV come from?

Coronaviruses are endemic to several species, and until 2019-nCoV popped up, there were five that could infect humans, says Tracey Goldstein, a wildlife infectious disease expert at the University of California, Davis. These spherical, 120 nm wide viruses have an RNA genome that is relatively unstable, and mutates frequently.

Goldstein says that 2019-nCoV is similar to the coronavirus that caused severe acute respiratory syndrome (SARS) in 2003, so it’s likely that transmission of the novel coronavirus is similar. Bats are the original reservoir for these viruses. Mutations to the viral genome allow a virus to infect a secondary animal, further mutations enable it to infect humans, and possibly more mutations allow it to quickly spread from human to human. The intermediate animal in the spread of the SARS virus was a cat-like creature called the civet. Researchers are still trying to figure out what the intermediate animal is for the novel virus.

This novel coronavirus is thought to have originated in a “wet” market in Wuhan City where live and dead animals are sold. Scientists report that live animals available at the market just before the outbreak included seafood, hedgehogs, badgers, snakes, and birds (bioRxiv 2020, DOI: 10.1101/2020.01.24.919183). These animal markets are considered a hot spot for cross-species transmission of viruses.

“The danger of zoonotic transmission was clear, so I was not completely surprised by the outbreak,” says Rolf Hilgenfeld, a researcher at the University of Lubeck who is currently in China to develop small-molecule inhibitors for coronaviruses. “But the timing was not predictable, and the magnitude is surprising.”


Mode of transmission
Bats harbor several coronaviruses, and some of these find their way to humans through an intermediate animal source. In the case of SARS, it was a cat called the civet. In the case of MERS, it was camels. Scientists are still trying to determine how the novel coronavirus jumped from animals to humans.

Description
Credit: C&EN/Shutterstock

SARS also made its zoonotic jump to people in a Chinese “wet” market. Peter Hotez, an infectious-diseases expert at Baylor College of Medicine, says that the Chinese government had an opportunity to prevent this outbreak. “After SARS happened, the government’s plan was to outlaw them, but clearly that law was not enforced,” he says.

Hilgenfeld says that the SARS coronavirus and 2019-nCoV are similar. The part of the glycoprotein that binds human cells on the novel coronavirus appears to be identical to the binding site of the SARS coronavirus glycoprotein, he says. Hilgenfeld and others think that the virus likely attaches to the same cell-surface molecule as the SARS virus does, angiotensin-converting enzyme 2 or ACE2 (bioRxiv 2020, DOI: 10.1101/2020.01.26.919985).

What are the characteristics of the disease?

According to the Centers for Disease Control and Prevention, coronaviruses, in general, cause respiratory illness, with fevers, runny noses, coughs, and sore throats. This new coronavirus appears to be no different. Disease severity for 2019-nCoV has been variable, with some people requiring hospitalization and others reporting mild symptoms.

The World Health Organization reported that the novel coronavirus’s R0, which is a number that describes a disease’s spread, is between 1.4 and 2.5, meaning every infected person will, on average, infect about two more people. A team of researchers in China calculated the R0 as between 2.24 and 3.58 (bioRxiv 2020, DOI: 10.1101/2020.01.23.916395). The R0 of seasonal flu is about 1.4, but varies. For measles, it’s between 12 and 18.

The Chinese government is reporting spread between humans who are not showing symptoms of the disease, so some virus carriers might be missed in these calculations.

Some infected people are being treated with interferon and a combination HIV drug called Kaletra (iopinavir and ritonavir) sold by AbbVie. Researchers from the Chinese Academy of Sciences have published a list of drugs they say could work against the coronavirus’s main protease, including the antibiotic colistin, several antitumor drugs, and perphenazine, an antipsychotic. Knocking out the virus’s protease prevents it from successfully replicating. Hilgenfeld hopes to collaborate with local Chinese researchers to test his inhibitor of the coronavirus main protease inhibitor on cells in culture. This α-keto amide compound works against the SARS virus, so he thinks it will also work on the novel coronavirus. He would still need to do clinical trials with the compound, so he has no illusions that his compound will be deployed during this outbreak.

UPDATE

On Feb. 11, 2020, the Coronavirus Study Group of the International Committee on Taxonomy of Viruses officially named the novel coronavirus "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2). The temporary name for the virus was 2019-nCoV.

This story was updated on Feb. 5, 2020, to change references of "the Wuhan coronavirus" to "the novel coronavirus" and "2019-nCoV" to reflect the World Health Organization's name for the virus.

This story was updated until Feb. 19, 2020.

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