The race to find a coronavirus treatment: One strategy might be just weeks away, scientists say – USA TODAY

As flu season comes to an end and allergy season starts to heat up, there may be concerns about symptoms that mimic the new coronavirus COVID-19. Wochit

MILWAUKEE, Wis. In a week whenthe coronavirus closures and quarantines hitlikefalling dominoes the lockdown in Italy,the emptyworkplaces and college campusesin the U.S., suspended sports seasons, canceled festivals far less attention fell on theglobal scientific community's driveto find treatments forthe new virus.

But researchers are already suggesting strategies tohelp patientssuffering from the virus, which is marked by fever, coughing and difficulty breathing. One treatment could be just weeks away.

With no vaccine expected anytime soon, treatmentsarecrucialtosaving the lives of thousands of the infected, especiallyhigh-riskpatients 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 Hospitalin 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."

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Kruse has been pursuing two different treatmentstrategies, one of which has a long history andcould be availablewithinweeks rather than months. The quickest option is likely to be the use ofantibodies from recovered COVID-19 patients. As of Saturday, there were almost 72,000 such patients worldwide. Thevirus 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 paperFriday 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 outthat serum from one recovered patient is only enough to save a singlesick one, explainedKruse 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 anothertechnique in a paper published in late Januaryin 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 externalportionof ACE-2, which would act as a decoy for the virus. Thevirus would bind tothe decoy, leaving it unable to reachtheactual door into the cell, and thus, unable tocause 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'sdecoy 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.

Afaster optioninvolves what's called "repurposing" a drug.

This is when a drug that has already been found safe and approved fortreatment of one disease also is foundusefulin treating another. One example is thedrug Sildenafil, which is sold as Viagra andused to treat both erectile dysfunction andpulmonary hypertension.

There are three ways in which scientists try to findan existing drug that can treat a new condition.

The rational method involves using drugs that have characteristics and targets that suggestthey might be used to treatthe 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 drugare beginning thismonth. Two more clinical trials of the drug are already underway in China.

In the U.S., the clinical trials process is slow and painstaking, takingseveral years andsometimes much longer.

Another approach to the new virus championed by numerous researchers isthe use oflab-made proteinscalled monoclonal antibodies.

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 thenext (outbreak)."

Monoclonal antibodies do havepitfalls. They require extensive testing. Also, viruses can mutate and escape from the antibodies. Companies sometimestarget two different parts of the virus to make it harder for the virusto mutate and elude the antibodies.

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 forcombating the new coronavirus will likely requirereaching patients early before they get too sick. Toward that end, Kruse said he believes the U.S. should pursue the much broader coronavirus testing policythat South Koreaadopted.

"Maybe in the next few weeks we will get to the point where we are testing everyone," he said.

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