Coronavirus: Virus provides leaps in scientific understanding

Author : suzathassan404

Publish Date : 2021-01-10 23:13:28

In January 2020, two scientists published the entire genetic code of a coronavirus that was soon to wreak havoc around the world. It marked the start of a year of intense and rapid scientific endeavour, to work out how we might fight the virus.

Eddie Holmes had the genetic blueprint for the coronavirus in his possession for exactly 52 minutes before he put it online.

Prof Holmes is based at the University of Sydney, where he works on the emergence of infectious disease - an area of research that was suddenly thrust into the spotlight at the beginning of 2020. He has worked closely, for several years, with Prof Yong-Zhen Zhang, who was at the Chinese Centre for Disease Control in Beijing.

Prof Zhang sequenced the genome of the virus that closed down the world.

Prof Zhang and Prof Holmes examine a rat in a trap during an infectious disease research trip to China in 2013
IMAGE COPYRIGHTEDDIE HOLMES
image captionProf Zhang and Prof Holmes examine a rat in a trap during an infectious disease research trip to China in 2013
He collected samples taken from some of the first patients in Wuhan Central Hospital, where a cluster of mysterious pneumonia cases had emerged. Many of those patients had a link to a seafood and wildlife market in Wuhan.

When he examined the code, Prof Zhang immediately saw that this was a coronavirus. It looked very similar to Sars - the respiratory disease that caused a deadly outbreak in Asia in 2002.

"That was on 5 January," recalls Prof Holmes. "And we just thought,oh no. It's Sars back again."

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Medical workers in protective suits with Covid-19 patients in Wuhan, China, 6 February 2020
IMAGE COPYRIGHTREUTERS
image captionMedical workers in protective suits with Covid-19 patients in Wuhan, China, February 2020
But this code - this virus - was different. It was new. Prof Zhang and Prof Holmes quickly submitted a paper describing what they had seen and, as the week wore on, a buzz of public health speculation about what the novel virus might be started on social media.

"I didn't sleep," Prof Holmes tells me. "It was weighing on my conscience." In Sydney, it was early on 11 January when Prof Holmes phoned his colleague in China and asked his permission to publish the sequence. "Zhang was on a plane, strapped into his seat," Prof Holmes recalled. "He told me he needed to think about it - there was some pressure not to release too much information about the outbreak.

Zhang and Holmes with colleagues at Wuhan Central Hospital
IMAGE COPYRIGHTEDDIE HOLMES
image captionProf Holmes (right) visited Wuhan Central Hospital with Prof Zhang and researchers from the Wuhan Centre for Disease Control in 2016
"He called me back about a minute later and said, 'OK, let's do it.'"

A researcher in Prof Zhang's lab emailed the genetic code to Eddie Holmes, who called a colleague in Edinburgh, in the UK. "It was about 01:00 there," Prof Holmes recalls.

In the ensuing 52 minutes, the scientists together wrote a brief post explaining that they were "releasing a coronavirus genome from a case of a respiratory disease from the Wuhan outbreak" and uploaded the code. Their post said that researchers should please "feel free to download, share, use and analyse this data".

With that post, the full genome of Sars CoV-2 - the code that makes the coronavirus - was available to any scientist with an internet connection.

The post on virological.org on 10 January 2020
IMAGE COPYRIGHTVIROLOGICAL.ORG
image captionThe researchers posted the full genome online on 10 January 2020
It set off 12 months of break-neck scientific endeavour. If you search the US National Library of Medicine - a database of published medical science studies - for mentions of Covid-19, you will retrieve more than 90,000 results.

"If we didn't collaborate with colleagues in China - if I wasn't working with and talking to Zhang - that sequence wouldn't have gone online as early as it did," says Prof Holmes.

That same weekend, scientists at a US pharmaceutical company called Moderna, which had never previously brought a product to market, downloaded the genome and started work on their experimental vaccine. Scientists at Pfizer did the same.

There are multiple methods - traditional and experimental - for making vaccines, but Moderna and Pfizer use an experimental approach based on something called mRNA (or Messenger ribonucleic acid). The terminology is a mouthful, but it describes a simpler, swifter approach to vaccine production. And it was boosted over the clinical finish line by the pandemic.

Margaret Keenan, 90, at University Hospital, Coventry - the first UK patient to receive the Pfizer-BioNTech Covid-19 vaccine - December 2020
IMAGE COPYRIGHTPA MEDIA
image captionMargaret Keenan, 90, who became the first person to receive the Pfizer-BioNTech vaccine outside of a trial, in December 2020
Vaccination is fundamentally based on "showing" your immune system the disease-causing agent, so it can form a biological memory and be primed to fight it. For many existing virus vaccines, this has meant producing versions or pieces of the virus itself - often snippets of viral protein stripped of their disease-causing ability. These are grown inside chicken eggs, packaged up and injected.

"To grow enough of those things can take a very long time - sometimes years," explains Prof Robert Langer, one of the founders of Moderna, and a professor of chemical engineering at the Massachusetts Institute of Technology (MIT) in Cambridge, US. "With mRNA - you use the body as a factory to make that protein. So rather than have a giant plant with all these eggs to grow your proteins, you just make the mRNA, give it to the patient and the patient does everything else."

Messenger RNA is a short sequence of coded genetic instructions for the protein you want a cell to make.

"I've been working on this technology for decades," says Prof Langer. "This is actually the ninth mRNA vaccine that Moderna has developed." The others, which include vaccines that are designed to prime people's immune systems to fight their own cancer, are still in clinical trials.

"But when the pandemic hit, this technology lent itself to doing things as rapidly as possible."

There are now more than 150 coronavirus vaccines in some stage of development. But Pfizer's mRNA vaccine, which it developed in partnership with the German company BioNTech, was the first to receive emergency authorisation by the US Food and Drug Administration. It was quickly followed by Moderna's vaccine - less than a year after scientists first downloaded the genome it was based on.

Researcher in a laboratory at Oxford’s Jenner Institute working on the coronavirus vaccine developed by AstraZeneca and Oxford University, December 2020
IMAGE COPYRIGHTPA/UNIVERSITY OF OXFORD
image captionResearcher in a laboratory at Oxford’s Jenner Institute working on the coronavirus vaccine developed by AstraZeneca and Oxford University
It was not until the end of January that the World Health Organization called the coronavirus outbreak a "public health emergency of international concern". And it took until March for the WHO to officially declare a pandemic. Efforts to understand the virus - to find out where it came from, how to treat it and learn how it was evolving - were already moving almost as rapidly as the pandemic.

"With that genome, we didn't need the actual virus," explains Dr Dalan Bailey from the UK's Pirbright Institute. "We could take that code and actually get the part of the virus that we wanted to study synthesised [using the genome as a blueprint] and have it in our lab within days.

"That definitely allowed us to start our research much more quickly."

Illustration of the coronavirus binding to a human cell
IMAGE COPYRIGHTSCIENCE PHOTO LIBRARY
image captionIllustration of the coronavirus binding to a human cell
Dr Bailey and his colleagues study how exactly the coronavirus latches on to and hijacks each cell. Key to this are those spikes we now see on every graphic depiction of the spherical coronavirus structure. Not only is the spike protein the key that unlocks viral entry into a cell, it is also the part of the virus that is most frequently recognised by our immune systems, so understanding its shape and its function is critical to optimising vaccines.

By the end of March, with many European countries in lockdown, Chinese scientists had mapped the exact atom-by-atom structure of that spike protein.

Knowing what the protein physically looks like means researchers can work out how antibodies bind to it. That is critical, because antibodies are the immune system's memory proteins. Immune cells produce antibodies to fit a specific invader - a virus that they have previously encountered in the

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Coronavirus: Virus provides leaps in scientific understanding

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