The science of fighting a virus: Multi-pronged global fight to defeat new coronavirus

Credit to Author: Randy Shore| Date: Fri, 21 Feb 2020 22:32:03 +0000

Scientists’ fight against COVID-19 ravaging China is two-pronged: Treatment and prevention.

Simply put, we need an antiviral treatment to reduce the severity of its symptoms and mortality associated with the illness, and a vaccine to prevent millions more people from catching it.

On the treatment front, there are about 90 existing treatments for such things as HIV, influenza A and malaria being tested on COVID-19 patients in China, according to Srinivas Murthy, an infectious disease specialist at B.C. Children’s Hospital.

“People are trying a lot of different things and hopefully something sticks,” he said.

More than 75,000 cases of COVID-19 have been confirmed worldwide since the new coronavirus first appeared less than three months ago and more than 2,000 people have died, mainly in China.

China’s National Center for Biotechnology Development confirmed this week that chloroquine, which is used to treat malaria, showed a “certain curative effect,” according to the website Clinical Trials Arena. The anti-flu treatment favilavir is also being tested, along with the experimental antiviral medication remdesivir, which can prevent MERS coronavirus in monkeys, according to China Daily. All three have show early signs of promise.

In Japan, chief cabinet secretary Yoshihide Suga confirmed that a medication developed to treat HIV is being considered for approval in a COVID-19 trial. “We’re currently preparing to start clinical trials using HIV medication on the novel coronavirus,” he said.

Dr. Srinivas Murthy. (Photo courtesy of UBCCourtesy UBC) PNG

Viruses are a very tricky adversary, according to Murthy.

People don’t generally seek care before they have symptoms, which is when the virus is running rampant through the body.

“Once the virus is disseminated around the body, your immune response to the virus is causing lots of symptoms,” he explained. “At that point, treating the virus is less important than treating the patient.”

“We don’t really have antivirals that treat an acute infection because it’s so difficult to identify patients and figure out when to give it,” said Murthy, who is also a clinical associate professor at UBC’s faculty of medicine.

Ideally, a treatment should be as specific as possible to the virus, exploiting a known weakness or in some cases composed of antibodies specific to the virus harvested from other patients.

The good news is that many antiviral medications work on any number of viruses that are closely related or have shared characteristics.

“We often repurpose antivirals for one kind of infection and use it for another infection,” he said.

At least a dozen pharmaceutical companies are working on a vaccine for COVID-19, including Johnson & Johnson, GlaxoSmithKline, Inovio, Novavax and Gilead.

The latest entrant, French drug giant Sanofi, has promised a vaccine ready for clinical trials in just 12 months, an achievement that normally takes 10 years.

In 2017, Sanofi acquired the vaccine development firm Protein Science, which has put considerable effort into a vaccine for SARS coronavirus in animal models, giving the company “a head start in expediting a COVID-19 vaccine,” Sanofi said in a statement.

“COVID-19 belongs to a family of coronaviruses that can cause respiratory disease,” the company added. “Sanofi plans to further investigate an advanced preclinical SARS vaccine candidate that could protect against COVID-19.”

Sanofi also has the potential to manufacture large quantities of the vaccine candidate by combining DNA code from the virus with an existing influenza vaccine.

Vaccines stimulate an immune response in a healthy person, so the body has the right weapons already at hand to fight the virus should the body come in contact with it.

Passengers wear masks in the international arrivals area at the Vancouver International Airport in Richmond on Jan. 23, 2020. JONATHAN HAYWARD / THE CANADIAN PRESS

The 2002 SARS coronavirus outbreak killed 774 people and sickened more than 8,000 in 26 countries. More than 400 Canadians got sick and 44 died.

It taught scientists some valuable lessons and triggered a radical rethink of vaccine development during a global emergency.

“SARS was still a major threat (in 2003),” UBC researcher Brett Finlay said after the outbreak. “We couldn’t afford to take the usual 10 years to develop a vaccine.”

Back then, UBC’s Michael Smith Genome Sciences Centre already had a plan to repurpose every lab in their control to the rapid sequencing of an infectious agent. And that’s exactly what happened.

With virus samples from a Canadian patient, the Smith scientists were able to generate a genome sequence of SARS-CoV in just six days, faster than anyone else in the world.

“The key to sequencing the genome so quickly was having a rapid response emergency management plan already in place,” wrote Finlay in Nature Reviews Microbiology.

“Our staff basically dropped everything to focus on SARS,” Dr. Marco Marra said years later. “From the National Microbiology Laboratory in Winnipeg, we obtained a small amount of viral RNA — five billionths of a gram — from a Toronto SARS patient who had died. Then we set about amplifying it.”

The newly formed SARS Accelerated Vaccine Initiative then pursued an unconventional fast-track approach to vaccine development, pursuing every stage in the development process simultaneously rather than in sequence, for three different vaccine candidates.

Two of the three prototype vaccines were being tested on animals within six months and the third within 12 months. Had the SARS outbreak continued, human trials would have come next.

“Newer technologies have improved vaccine development, but the principles still apply, and (scientists) can learn from these lessons,” Finlay said in an email.

Indeed, potential SARS vaccines abandoned years ago may prove central to the push to contain COVID-19.

The good news is that COVID-19 and SARS-CoV are genetically similar. The bad news is that COVID-19 could well continue to mutate while scientists work on a vaccine.

Tracy Lee and Becky Hickman are sequencing COVID-19 viruses at the B.C. Centre for Disease Control Public Health Laboratory as part of a tracking program funded by Genome B.C. Michael Donoghue / PNG

Creating a vaccine starts with examining which tools the body uses to fight the infection.

In the case of SARS, three candidates emerged: potent neutralizing antibodies that identify and attack the virus and two different kinds of T cells, which seek out and destroy infected cells.

“Taken together, the data indicated that a vaccine for SARS would need to induce neutralizing antibodies and, possibly, CD4+ and CD8+ T-cell responses,” Finlay wrote with co-authors Raymond See and Robert Brunham.

Using samples taken from infected COVID-19 patients, vaccine architects will look for signals that indicate how the body is fighting back.

“In response to any virus, there are a variety of immune responses. We need to decide which ones to harness to best protect ourselves,” said Murthy. “You exploit your body’s natural reaction to the virus and try to mimic that as best you can with a vaccine.”

The effectiveness of potential human vaccines are then tested in a variety of animals that, to a greater or lesser degree, match human immune responses. Mice, rats, macaque monkeys and especially ferrets may prove useful.

“We need a consistent animal model that reflects human biology, and people are still working on refining that right now,” said Murthy.

The biological model for SARS-CoV was developed in ferrets and that work will likely provide scientists with a running start on COVID-19.

A bus transports British passengers after they left the coronavirus-hit cruise ship Diamond Princess at the Daikoku Pier Terminal in Yokohama, south of Tokyo, Japan, on Feb. 22, 2020. Kim Kyung-Hoon / Reuters

More than 500 British Columbians have been tested for COVID-19 and just six cases have been confirmed, according to the provincial health officer, Dr. Bonnie Henry. Most of them are listed as recovering.

Several hundred Canadians who may have come in contact with the virus have been quarantined in military facilities at Trenton, Ont. Forty-three Canadians who were quarantined on a cruise ship off the coast of Japan are among the confirmed cases of COVID-19.

With funding from Genome B.C., the B.C. Centre for Disease Control will use genomic analysis to track the virus and its evolution should it spread further in British Columbia.

As clusters of cases spring up in different parts of the world, COVID-19 could branch off into distinct strains that can be identified by their genetic makeup.

“From the sequences that are in the public domain, we can see strains of COVID-19 separating and evolving into different groups,” said Dr. Richard Harrigan, a professor in UBC’s faculty of medicine.

A COVID-19 infection from China could be distinguished from a cluster in California or the U.K., which would provide important information about how the virus is getting into B.C.

“It tells the public health system where they should be looking,” he said. “If cases are popping up around the province from different parts of the world, they may take a very different approach to screening.”

— With a file from Reuters

rshore@postmedia.com

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