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<![CDATA[Labouring laboratory scientists make up other front line in Covid-19 fight]>

As medical staff around the world receive deserved praise for their dogged work helping those infected with Covid-19, a less visible group is also in the trenches in another frontline fight against the disease.

While hundreds of millions of people stay home to stem the spread of the coronavirus, scientists are working on closed campuses and in near-empty laboratories to try and break the secrets of the virus and find a way to disarm it.

Getting to the lab can be a frigid commute by bicycle amid national lockdowns and stringent social distancing measures. Then it is long hours in what can be lonely labs, employing the tools of modern science to try and find a way to help pull the rest of the population back to normalcy.

Marjolein Kikkert, a researcher and associate professor at the Leiden University Medical Centre in the Netherlands, has been handling dangerous coronaviruses in a biosafety level-three lab for years.

She is one of a small number of researchers around the world who study this family of viruses. But this is the first time she has had to follow the strict safety protocols of her high-security lab while working with a pathogen she is more likely to get exposed to on the streets.

Battling this virus, which has killed more than 190,000 people around the world and continues to spread, was a whole different experience, she said.

"I feel I have never worked as hard in my life, and my feeling is that I'm racing all the time, and kind of waiting for the time when this is slowing down and I can look back and think 'what happened here?'" Kikkert said.

Her routine includes dropping off her two children at their officially closed school, a public service offered for the country's essential workers. Then it is rotating shifts at the lab, testing vaccine candidates and observing immune responses, and sharing information with collaborators.

She and her colleagues, a band of virologists and immunologists, are among the few groups around the world focusing on nidoviruses, an order of pathogens that includes coronaviruses like the one that causes Covid-19.

Their work to fight the current pandemic started in earnest in February, after a scramble to get the thing they needed to start their research: the live virus.

It arrived on a flight from Australia in multilayered, high-security certified packaging via a specialised courier service. It was sent from researchers in Melbourne who had isolated a strain from one of the earliest identified Covid-19 patients outside China.

From there the Leiden team began its work: testing how the virus fares in blood samples from mice who have been given vaccine candidates, and in infected cell cultures treated with antiviral compounds. The aim is to help advance the search for a vaccine or drug for the disease that has infected over 2.6 million worldwide.

For researcher Arnab Chatterjee in California, his race against the Covid-19 clock started on January 22, about three weeks after the first announcements of the outbreak of a novel coronavirus in China.

At that time, Chatterjee, who is vice-president of medicinal chemistry at the California Institute for Biomedical Research (Calibr) at Scripps Research Institute, began coordinating the first shipment of a package of drug compounds that is about the size of an aeroplane carry-on bag.

Inside were 12,000 compounds, representing nearly all the molecules that have been used clinically or vetted for safe use in medicines. Exactly 20 milligrams of each are stored on 30 four-by-six inch plates inside the box.

Known as the ReFRAME drug repurposing collection, it has since been sent or is in the process of going out to around 20 lab research teams around the world. They use it to screen for compounds that might be effective in stopping Sars-CoV-2 from attacking human cells.

The library, developed with support from the Bill and Melinda Gates Foundation, was designed with this kind of scenario in mind: a shared resource to find cures and share data.

"It allows many researchers to address a problem using exactly the same toolset," said Chatterjee, adding that at the Calibr lab, safety measures meant five out of the lab's 130 members were working on-site doing their own screening work.

As the virus began to spread, halting economies and forcing lockdowns, so did the urgency of getting those packages out, he said.

In some cases, he decided to ship out the suitcase of compounds even before agreements with collaborators were finalised, in case there was a "breakdown of basic shipment and import-export procedures".

Breakdowns of basic procedures have become the global norm during the pandemic, and science is no exception.

In many countries the only laboratories allowed to remain open are those working on coronavirus research. There, too, even as the usual laboratory protocols remain, new safety measures add restrictions.

Balancing these measures with the urgency of the work is challenging according to Ooi Eng Eong, a professor of emerging infectious diseases at Duke-NUS Medical School in Singapore, where there has been a recent spike in Covid-19 cases.

Researchers in Ooi's lab have split into two shifts to minimise contact, even as they are using a genetic screening technique to take an mRNA vaccine candidate into phase one human trials by midsummer " a process that might typically be expected to take five years.

"We try to minimise the deceleration of our pace as much as we can. Those that come in the morning, they'd sometimes start much earlier than a normal work day, those who come in the afternoon, they sometimes don't go home until late at night, we try to do our best given the hours we can work," he said.

"It's a bit of a shame that in a crisis like this, those of us that may have the capacity to contribute to accelerate vaccines and drugs for clinical applications will be held back by the overall control measures."

Still, he is hopeful that his lab's screening techniques and the technology behind the mRNA vaccine candidates, produced by their partner at California-based Arcturus Therapeutics, will keep them on schedule.

"There's a lot of urgency, but for scientists it's challenges like these that keep us going," Ooi said.

In New York, which at one point became a global epicentre of the disease, researchers at Florian Krammer's lab at the Icahn School of Medicine at Mount Sinai work long shifts and weekends. They are limited to just a few researchers in a room at a time.

The previous open lab culture is no more " doors are closed, interactions are limited, masks are on. The building is empty of non-Covid researchers. Parts of the building are shuttered " including the cafeteria where they usually get their coffee.

But members of his team push on, he said, assembling the viral proteins that hospitals can use to identify patients who could donate blood plasma for an experimental treatment being used for Covid-19 patients.

"If my lab doesn't produce the proteins that they need, they need to stop screening, which means they can't get any plasma donors," said Krammer, a professor of microbiology. "It's also emotionally straining in that you know that there are people who get treated with this, and the everyday question of how they are doing."

His lab developed one of the first antibody tests in the United States for Covid-19, which last week was granted emergency approval by the US Food and Drug Administration.

They have also shared the toolkit for making the tests, which can check if people have an immune response to Covid-19, with over 200 laboratories around the world.

Amid New York's stay-at-home order, Krammer has told his researchers who have to commute that they do not need to come in, while those who can walk or bike still show up. Donations are helping pay for some Ubers.

They have letters stating they are essential workers, exempted from New York's stay-at-home rules, just in case they are stopped on the way to work.

The team, which usually focuses on influenza and hantavirus, started to put that work aside in January as they saw an urgent need for research into the newly emerged coronavirus. It was all part of what it meant to be in the field, Krammer said.

"We are virologists, we are here to deal with this ... We have to do what we have to do."

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This article originally appeared on the South China Morning Post (SCMP).

Copyright (c) 2020. South China Morning Post Publishers Ltd. All rights reserved.

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