Story of scientists’ race to find treatment
Vaccine not expected soon, but ‘right’ ideas promise hope for help
In a week when the COVID-19 closures and quarantines hit like falling dominoes — the lockdown in Italy, the empty workplaces and college campuses in the U.S., suspended sports seasons, canceled festivals — 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 disease, which is marked by fever, coughing and difficulty breathing. One treatment could be just weeks away.
With no vaccine expected anytime soon, treatments are crucial to saving the lives of thousands of the infected, especially high-risk patients — 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.”
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 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.
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.
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.
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.