In a week when the coronavirus closures and quarantines hit like falling dominoes β the lockdown in Italy, the empty workplaces and college campuses in the U.S., suspended sports seasons, canceled festivals β far less attention fell on the global scientific community's drive to find treatments for the new virus.
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The race to find a coronavirus treatment
1. The race to find a coronavirus treatment: One
strategy might be just weeks away, scientists
say
MILWAUKEE, Wis. β In a week when the coronavirus closures and quarantines hit
like falling dominoes β the lockdown in Italy, the empty workplaces and college
campuses in the U.S., suspended sports seasons, canceled festivals β far less
attention fell on the global scientific community's drive to find treatments for the
new virus.
But researchers are already suggesting strategies to help patients suffering from
the virus, which is marked by fever, coughing and difficulty breathing. One
treatment could be just weeks away.
2. With no vaccine expected anytime soon, treatments are crucial to saving the lives
of thousands of the infected, especially high-risk patients β the elderly, those with
compromised immune systems and those with chronic illnesses, such as diabetes,
heart disease and lung disease.
"I'm very hopeful and very positive. We'll get through this," said Robert Kruse, a
doctor in the Department of Pathology at Johns Hopkins Hospital in Baltimore.
"I've been shocked this week at the measures that have been taken (to alter daily
life). They were probably the correct ones, given that they have worked in other
countries."
'Time is of the essence'
Kruse has been pursuing two different treatment strategies, one of which has a
long history and could be available within weeks rather than months. The quickest
option is likely to be the use of antibodies from recovered COVID-19 patients. As
of Saturday, there were almost 72,000 such patients worldwide. The virus has
infected about 150,000, killing more than 5,500.
The use of survivor antibodies, serum therapy, dates back to 1891 when it was
used successfully to treat a child with diphtheria. Since then, serum from
recovered patients has been used "to stem outbreaks of viral diseases such as
poliomyelitis, measles, mumps and influenza," according to a paper Friday in The
Journal of Clinical Investigation.
"As we are in the midst of a worldwide pandemic, we recommend that institutions
consider the emergency use (of serum from recovered patients) and begin
preparations as soon as possible. Time is of the essence," wrote the paper's two
authors, Arturo Casadevall of Johns Hopkins School of Public Health, and
Liise-anne Pirofski of the Albert Einstein College of Medicine in New York.
All of the strategies, including the use of serum from recovered patients, have
drawbacks. Transfusion of serum carries potential side effects, including fever,
allergic reactions, and a very small risk of infectious disease transmission.
Collecting large amounts of serum from recovered patients could be a sizable task.
It could turn out that serum from one recovered patient is only enough to save a
3. single sick one, explained Kruse at Johns Hopkins. "It's a logistical challenge to put
it together, but at the very least there are no hurdles (from the U.S. Food and
Drug Administration) to producing the therapy."
Kruse advanced another technique in a paper published in late January in the
journal F1000 Research.
His method seeks to take advantage of the new coronavirus' ability to latch onto
and enter cells.
Scientists often talk about "cell receptors," which are essentially doors that allow a
virus to enter the cell.
The "door" the new coronavirus is entering through is known as the ACE-2
protein. Kruse's technique involves detaching the external portion of ACE-2, which
would act as a decoy for the virus. The virus would bind to the decoy, leaving it
unable to reach the actual door into the cell, and thus, unable to cause infection.
"It won't realize, 'Oh gosh, this isn't a cell,'" Kruse explained in an interview. "The
virus can't mutate away from this."
Kruse's decoy therapy would not be available until fall at the earliest. However, a
similar version of the strategy is currently being tested in trials in China.
Using a drug for a new purpose
A faster option involves what's called "repurposing" a drug.
This is when a drug that has already been found safe and approved for treatment
of one disease also is found useful in treating another. One example is the drug
Sildenafil, which is sold as Viagra and used to treat both erectile dysfunction and
pulmonary hypertension.
4. There are three ways in which scientists try to find an existing drug that can treat
a new condition.
The rational method involves using drugs that have characteristics and targets
that suggest they might be used to treat the new condition.
The computational method involves examining protein structures and using them
to predict an existing drug that might work.
The final method takes advantage of the vast drug libraries possessed by
companies and academic institutions. High-speed technology allows researchers
to screen thousands of drugs very quickly to determine whether they will act
against a specific target.
Considerable hope, interest and money have been invested in one drug not
previously approved, remdesivir. The drug was previously tested against Ebola,
but failed in trials.
Gilead Sciences, a Foster City, California-based biopharmaceutical company,
announced that two clinical studies of the drug are beginning this month. Two
more clinical trials of the drug are already underway in China.
In the U.S., the clinical trials process is slow and painstaking, taking several years
and sometimes much longer.
'The idea is right'
Another approach to the new virus championed by numerous researchers is the
use of lab-made proteins called monoclonal antibodies.
5. These confer what's called "passive immunity" and have been used previously to
treat cancer, multiple sclerosis, cardiovascular disease and many other conditions.
"The use of monoclonal antibodies is a new era in infectious disease prevention
which overcomes many drawbacks associated with serum therapy ... in terms of
specificity, purity, low risk of blood-borne pathogen contamination and safety,"
wrote the authors of a recent paper in the Asian Pacific Journal of Allergy and
Immunology.
The biotechnology company Regeneron, based in Tarrytown, New York, started
work searching for a monoclonal antibody "for this particular virus in
early/mid-January," said Christos Kyratsous, the company's vice president for
infectious diseases and viral vector technologies. "But really we started working
on it decades ago when we began building our unique end-to-end drug discovery
and development technologies."
Gregory Poland, director of Mayo Clinic's Vaccine Research Group, said the use of
monoclonal antibodies "needs to be designed and tested in this specific disease,
but I wouldn't see any reason it wouldn't work. The idea is right."
Like other scientists, Poland was less hopeful that a vaccine would be developed
anytime soon.
"We won't have a vaccine for this outbreak," he said. "It will be before the next
(outbreak)."
Monoclonal antibodies do have pitfalls. They require extensive testing. Also,
viruses can mutate and escape from the antibodies. Companies sometimes target
two different parts of the virus to make it harder for the virus to mutate and elude
the antibodies.
6. Ajay K. Sethi, associate professor of population health sciences at the University of
Wisconsin-Madison, expressed support for the development of monoclonal
antibodies.
"In my opinion, trying a strategy like monoclonal antibodies to provide passive
immunity is a good idea," Sethi said. He added that given the technique's past
successes, "it is hopeful, but not surprising."
Strategies for combating the new coronavirus will likely require reaching patients
early before they get too sick. Toward that end, Kruse said he believes the U.S.
should pursue the much broader coronavirus testing policy that South Korea
adopted.
"Maybe in the next few weeks we will get to the point where we are testing
everyone," he said.