Huge potential in studying the tiny: Sequencing genome of coronavirus from Wuhan could lead to vaccines

A laboratory assistant prepares a test for the coronavirus at the Amedeo di Savoia hospital in Turin, Italy, on Jan 30, 2020.
A laboratory assistant prepares a test for the coronavirus at the Amedeo di Savoia hospital in Turin, Italy, on Jan 30, 2020.PHOTO: EPA-EFE

SINGAPORE - Even as efforts to contain the outbreak are being ramped up, scientists are hard at work to understand the genome of the coronavirus which originated in Wuhan, China.

The genetic material encodes information that is critical in helping scientists develop a diagnostic test and a vaccine for the coronavirus, which has killed more than 400 people and infected tens of thousands since the world first heard of it about a month ago.

The genome of the coronavirus was first uploaded on a public database in early January by scientists in China.

Since then, researchers around the world have been trying to sequence the genome of the virus from samples taken from patients.

Doctors and scientists from Duke-NUS Medical School, Singapore General Hospital, National Centre for Infectious Diseases and the Ministry of Health have successfully cultured the coronavirus from an infected patient's clinical sample, only the third country in the world outside of China to do so.

The impact of genomic research

Without a host, viruses are just genetic material encased in a protein shell - they cannot reproduce without infecting a mammalian host cell, and they essentially just exist, said cell biologist Ong Siew Hwa, director and chief scientist at home-grown biotech company Acumen Research Laboratories, who spoke to The Straits Times about the importance of studying the genome of the coronavirus.

In fact, if a virus is outside a host body, many scientists would not consider them living things.

But when viruses latch on to a host cell - in the case of the coronavirus, their mammalian hosts are human - they shed their innocuous nature.

The virus takes over the cellular machinery of the host cell and hijacks it to produce more viral genetic material, on top of the work the machinery does in producing molecules to keep the host healthy and alive.

 
 
 

How do the viruses hijack cells? It all boils down to their genetic make-up.

Viruses of the family Coronaviridae, which includes the new coronavirus, possess a single-strand RNA genome.

Generally, RNA contains instructions that "tell" a cell what proteins to produce.

So if a host cell is infected by a virus, it goes rogue - the cell takes its cue now from the viral RNA, and produces additional types of proteins than what it is used to.

For patients infected with the coronavirus, these additional proteins could lead to an inflammation of the lung tissue and cause pneumonia-like symptoms.

Said Professor Lisa Ng, a senior principal investigator at the Singapore Immunology Network at the Agency for Science, Technology and Research (A*Star): "Infection with viruses sometimes cause exuberant immune responses known as 'cytokine storms'. This means excessive levels of pro-inflammatory cytokines will be produced."

She added that the production of various pro-inflammatory cytokines will lead to inflammation of the lung tissues.

"Prolonged inflammation could lead to widespread tissue damage. In this case, some of the lung tissues of coronavirus-infected patients may be damaged," said Prof Ng.

Implications on human health

The genome of a virus is more than just a package of instructions for a host cell.

Its genome is also unique to it, and can function as a "fingerprint" that helps scientists distinguish it from other viruses.

The genome has yielded multiple insights, said Dr Ong.

First, just as how decoding the human genome enabled scientists to establish the evolutionary relationship between humans and chimpanzees, the virus' genome has allowed scientists to confirm that the new coronavirus is closely related to the virus that caused the severe acute respiratory syndrome (Sars) in 2003.

This could mean that scientists can build on previous research undertaken for a Sars vaccine, instead of starting from scratch, said Dr Ong.

She explained: "This close relationship could mean that a vaccine or anti-viral treatment for Sars, if available, could be used to treat patients infected with the novel coronavirus."

Already, China has started a clinical trial to test Remdesivir, a new antiviral drug by Gilead Sciences aimed at infectious diseases such Ebola and Sars.

Doctors at the Beijing-based China-Japan Friendship Hospital are testing the drug for efficacy in treating the deadly new strain of coronavirus, Bloomberg reported.

Second, the availability of the genome of the virus means that diagnostic kits can be developed, said Dr Ong, whose company Acumen Research Laboratories has developed such a kit for the coronavirus.

"Such a test can help clinicians quickly separate patients infected by the novel coronavirus from other patients with pneumonia-like symptoms, allowing both groups to get the treatment they need," she told ST.

The war against coronavirus

Genetic work is a crucial tool in the world's fight to control the outbreak of the coronavirus, but it should not be the only weapon in the armoury, say experts.

 
 

Clinical studies of patients already infected with the virus are also important, said Dr Ong.

For one thing, this will allow scientists to determine if the composition of the blood (which includes virus-fighting antibodies) of patients changes over time.

Such studies could also allow clinicians to identify if there are any similar genetic traits among the patients who develop more severe infections, known as sepsis, said Dr Ong.

"If doctors can identify patients who are more at risk of developing severe complications based on certain genetic traits, or DNA biomarkers, it could help them determine which patients to send to intensive care units (ICUs)," she said.

"ICUs are a precious resource in hospitals, so being able to identify patients who are more at risk of developing severe pneumonia at an earlier stage could help them manage resources and save lives," she added.

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