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Repurposed Drugs Offer Shortest Path to Coronavirus Treatment 


A laboratory technician prepares COVID-19 patient samples for semi-automatic testing at Northwell Health Labs, March 11, 2020, in Lake Success, N.Y.
A laboratory technician prepares COVID-19 patient samples for semi-automatic testing at Northwell Health Labs, March 11, 2020, in Lake Success, N.Y.

With the global COVID-19 death toll surging past 20,000 people this week, accelerated efforts to develop coronavirus treatments are primarily focused on adapting existing drugs intended to fight other diseases.

“The shortest path to a treatment, we think, is to repurpose something that already exists based on our knowledge of the mechanisms of action," said Dr. Hana Akselrod, an assistant professor of infectious diseases at the George Washington University School of Medicine and Health Sciences.

Repurposed Drugs Offer Shortest Path to Coronavirus Treatment
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This new strain of coronavirus causes the disease, COVID-19, a respiratory illness that can be fatal for an estimated 2% of the population, especially older people and those with underlying medical conditions, such as diabetes and high blood pressure. COVID-19 virus is related to other deadly viruses that have caused relatively recent widespread outbreaks: SARS, severe acute respiratory syndrome, and MERS, Middle East respiratory syndrome.

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Infectious disease experts are confident that a vaccine can be developed to prevent coronavirus infections, but trials and testing to develop a safe and effective vaccine and to scale up worldwide production of the treatment could take a year or longer.

No proven coronavirus treatment currently exists for infected patients, but a range of drugs are being tested that fall under three main categories of intended results: neutralize the virus itself, alleviate some of its life-threatening symptoms, and boost a patient’s immune system to fight off the infection.

Researchers work with coronavirus samples as a trial begins to see whether malaria treatment hydroxychloroquine can prevent or reduce the severity of the coronavirus, at the University of Minnesota in Minneapolis, March 19, 2020.
Researchers work with coronavirus samples as a trial begins to see whether malaria treatment hydroxychloroquine can prevent or reduce the severity of the coronavirus, at the University of Minnesota in Minneapolis, March 19, 2020.

Neutralize virus

Older malaria drugs, chloroquine and hydroxychloroquine, are being studied in a number of countries to possibly prevent coronavirus infection or kill off the virus in early stages of infection. This is a drug combination that President Donald Trump called a “game changer” - but scientists caution more study is needed to verify results.

How does chloroquine and hydroxychloroquine work?

“The going theory is that this drug interferes with the virus’s ability to enter the host cell, and makes the cell less hospitable to the virus. And if the virus is not infecting the cell, it would not be as effective at reproducing and creating more copies of itself, and so on and so forth,” said Dr. Akselrod.

This malaria drug cocktail has been tried in small group studies in France and China with mixed results. Larger studies are now underway.

Even if chloroquine and hydroxychloroquine prove effective against coronavirus, there are serious possible side effects to consider, including possible heart arrhythmias or irregular beats of the heart, and it can be toxic if taken at too high a dosage.

“We also know that there are already cases where people thought they could keep safe from COVID-19 by taking this drug and tragically end up poisoning themselves,” said Akselrod.

Another drug called remdesivir that proved ineffective to treat patients infected with the deadly Ebola virus, has shown promise in treating COVID-19 patients. Like the malaria drug, remdesivir also inhibits the coronavirus from entering the host cell and reproducing. Large scale trials are underway for this drug as well.

A laboratory technician prepares COVID-19 patient samples for semi-automatic testing at Northwell Health Labs, March 11, 2020, in Lake Success, N.Y.
A laboratory technician prepares COVID-19 patient samples for semi-automatic testing at Northwell Health Labs, March 11, 2020, in Lake Success, N.Y.

Alleviating symptoms

The COVID-19 virus attaches to the lungs, causing in many cases severe inflammation, congestion, breathing problems, pneumonia and respiratory failure.

A rheumatoid arthritis medication called Kevzara is among the drugs being tested to treat COVID-19 symptoms. This drug targets a part of the body’s own immune system.

How does Kevzara work?

“It interferes with an important part of the inflammatory cascade, which is part of the body's defense mechanism in response to an overwhelming infection. The theory with these drugs is that by blocking the cascade, and this is after infection has already occurred and already developed, perhaps the severity of the effect of the virus and the severity of the symptom can be reduced by blocking this part of the immune response,” said Akselrod.

While Kevzara and other anti-inflammatory drugs could help relieve congestion and respiratory problems caused by the coronavirus, there are concerns they could also interfere with the immune system’s ability to fight the infection.

The malaria drugs chloroquine and hydroxychloroquine also have anti-inflammatory properties that could help relieve coronavirus-related congestion.

View of a lab in the vaccine innovation department at Pasteur Institute in Paris, Feb. 6, 2020.
View of a lab in the vaccine innovation department at Pasteur Institute in Paris, Feb. 6, 2020.

Boosting immunity

The U.S. Food and Drug Administration this week approved convalescent plasma therapies to treat seriously ill coronavirus patients. This involves extracting antibodies from the blood plasma of coronavirus patients that have fully recovered, or convalesced, and injecting them into ill patients.

“What we're doing is this low tech, old style solution of taking it from (recovered) people, just like people did before antibiotics were invented,” said Dr. Shmuel Shoham, an associate professor of medicine at Johns Hopkins University School of Medicine, who is part of the team that has tested convalescent plasma on different types of influenza.

Using convalescent plasma on seriously ill patients may be worth trying, Dr. Shoham says, but past tests during later stages of infection have not proven effective. Instead, he says, it “makes more sense scientifically” to use this process for prevention and for early treatment.

A recent coronavirus treatment failure was a drug treatment for human immunodeficiency virus (HIV) that proved ineffective in a recent trial.

Nearly 70 existing drugs have been identified that could prevent or treat COVID-19, according to the biological science web site bioRxiv.

Infectious disease experts are reluctant to speculate on how long it will take for coronavirus treatments to complete the testing and approval process, and for pharmaceutical companies to scale up production to meet the worldwide need, but they say at the very least it will take months.

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