Pick of the coronavirus papers: A viral enzyme’s structure points to possible drugs

Fresh findings about SARS-CoV-2 and the disease it causes.

10 April — A viral enzyme’s structure points to possible drugs

Scientists have detailed the crystal structure of one of SARS-CoV-2’s key proteins, an enzyme called a protease that the virus needs to replicate within our cells.

Hualiang Jiang, Zihe Rao and Haitao Yang at ShanghaiTech University in China and their colleagues deposited the structure in a protein data bank two months ago, and have since used it to help them identify compounds that inhibit the protease (Z. Jin et al. Nature; 2020). The team’s screening revealed several powerful viral inhibitors, including ebselen, whose safety has already been tested in people.

These inhibitors work by infiltrating a hollow in the protease. Proteases found in other coronaviruses have a similar hollow, raising hopes that a single compound might help to treat a wide variety of diseases caused by coronaviruses.

9 April — Absent antibodies suggest mystery immune response

After recovering from infection with SARS-Cov-2, many people have high levels of antibodies against the virus. But a recent study finds that in some recovered patients, such antibodies are present at very low levels — and in some cases are undetectable.

When a foreign microbe intrudes on the body, the immune system usually makes proteins called antibodies that help to fight off the invader. A team led by Jinghe Huang and Fan Wu at Fudan University in Shanghai, China measured antibodies to the novel coronavirus in 175 volunteers who had recovered from mild infections (F. Wu et al., 2020). About 30% of the volunteers — and especially those under the age of 40 — never developed high levels of SARS-CoV-2 antibodies, suggesting that other immune responses helped rid them of their infections.

8 April — Viral load soars as infected people start feeling ill

Viral RNA levels are highest in people with COVID-19 soon after their symptoms appear, according to two separate research teams.

Kwok-Yung Yuen at The University of Hong Kong–Shenzhen Hospital, China, and his colleagues analysed saliva samples coughed up by 23 people infected with SARS-CoV-2. The team found that study participants’ viral concentrations peaked shortly after they started feeling ill, and began declining about one week after the peak.

The more viral RNA detected in a person’s body, the more they excrete when coughing or sneezing. The authors say that the high levels of SARS-CoV-2 particles detected at the onset of symptoms suggest that the virus can be transmitted easily between people, even when symptoms are relatively mild (K. K.-W. To et al. Lancet Infect. Dis.; 2020).

The results are consistent with another study of nose and throat swabs from 18 people with COVID-19. The concentrations of viral RNA in the 17 symptomatic patients were similar to that in the one asymptomatic patient (L. Zou et al. N. Engl. J. Med.; 2020).

However, another study found that people with milder COVID-19 symptoms on admission to hospital had much lower concentrations of viral RNA than did those with more severe symptoms (Y. Liu et al. Lancet Infect. Dis.; 2020). Wei Zhang at The First Affiliated Hospital of Nanchang University, China, Leo Poon at the University of Hong Kong, and their colleagues say the findings suggest that viral RNA concentrations could predict whether infected people will develop more severe symptoms.

7 April — A comparison finds subtle differences between tests for the COVID-19 virus

Doctors rely on a test called quantitative reverse-transcription polymerase chain reaction (qRT-PCR) to determine whether a person is infected with SARS-CoV-2. A team led by Nathan Grubaugh at Yale School of Public Health in New Haven, Connecticut, compared nine widely used versions of the test and found that all of them reliably detect the virus (C. B. F. Vogels et al. Preprint at medRxiv; 2020).

But the researchers also found that some tests — including one made by the US Centers for Disease Control and Prevention, another developed at Hong Kong University, and a third from Charité–Universitätsmedizin Berlin — performed best when it came to detecting low levels of the virus in samples.

5 AprilBats harbour a pool of coronaviruses related to pandemic culprit

Viruses closely related to SARS-CoV-2, the virus causing the COVID-19 pandemic, have been circulating in horseshoe bats, ready to jump to humans, for decades — and maybe even longer.

David Robertson at the University of Glasgow, UK, and his colleagues analysed the RNA of 68 coronaviruses, including SARS-CoV-2 and the virus that causes severe acute respiratory syndrome, or SARS (M. F. Boni et al. Preprint at bioRxiv; 2020). This analysis shows that horseshoe bats (Rhinolophus spp.) host an expanding lineage of viruses that, like SARS-CoV-2, can infect humans. The team estimates that the ancestor of SARS-CoV-2 split 40 to 70 years ago from the closely related bat virus RaTG13. Though the two viruses are highly similar genetically, RaTG13 doesn’t infect humans.

The analysis also suggests that viruses in the lineage are ready to jump to humans directly from bats. But SARS-CoV-2 might have first hopped to another species that humans are more exposed to, rather than spreading straight from bat to human.

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