COVID-19, the infection caused by the newly identified coronavirus, is a currently a disease with no pharmaceutical weapons against it. There’s no vaccine to prevent it, and no drugs can treat it. But researchers are racing to change that. A vaccine could be ready to test as soon as April. More than two dozen studies have already been registered on ClinicalTrials.gov, a website that tracks research. These studies aim to test everything from traditional Chinese medicine to vitamin C, stem cells, steroids, and medications that fight other viruses, like the flu and HIV. The hope is that something about how these repurposed remedies work will help patients who are desperately ill with no other prospects. Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, says this is all part of the playbook for brand-new diseases. “There’s a lot of empiric guessing,” he says. “They’re going to propose a whole lot of drugs that already exist. They’re going to say, here’s the data that shows it blocks the virus” in a test tube. But test tubes aren’t people, and many drugs that seem to work in a lab won’t end up helping patients. Coronaviruses are especially hard to stop once they invade the body. Unlike many other kinds of viruses, they have a fail-safe against tampering -- a “proofreader” that constantly inspects their code, looking for errors, including the potentially life-saving errors that drugs could introduce. Fauci says researchers will be able to make better guesses about how to help people when they can try drugs in animals. “We don’t have an animal model yet of the new coronavirus. When we do get an animal model, that will be a big boon to drugs because then, you can clearly test them in a physiological way, whether they work,” he says. Looking to Drugs for HIV and Flu One of the drugs already under study is the combination of two HIV medications: lopinavir and ritonavir, brand-named Kaletra. Kaletra stops viruses by interfering with the enzymes they need to infect cells, called proteases. One study being done at the Guangzhou Eighth People’s Hospital in China is testing Kaletra against Arbidol, an antiviral drug approved in China and Russia to treat the flu. Two groups of patients will take the medications along with standard care. A third group in the study will receive only standard care, typically supportive therapy with oxygen and IV fluids that are meant to support the body so the immune system can fight off a virus on its own. An Ebola Drug Gets a Second Look One repurposed drug generating a lot of buzz is an experimental infusion called remdesivir. It was originally tested against Ebola. While it didn’t work for that infection, it has been shown to shut down the new coronavirus, at least in test tubes. It’s been given to a small number of COVID-19 patients already, including one in Washington state. In order to have better evidence of how well it may work in people, two studies in Beijing are comparing remdesivir to a dummy pill to see if the drug can help patients with both mild and severe symptoms recover from their illnesses. Viruses work by infecting cells, taking over their machinery, and getting them to crank out more copies of the virus, which then goes on to infect more cells. Remdesivir is a mimic that fools a virus into replacing one of its four building blocks with a chemical fake. Once in the virus’s blueprints, the imposter acts like a stop sign that keeps the virus from copying itself. Other kinds of drugs in the same class -- called nucleotide analogs -- are used to attack cancer and other infectious viruses like hepatitis B. Last week, Chinese scientists published a study showing remdesivir was effective against the new coronavirus, 2019-nCoV. Out of seven drugs tested, only remdesivir and an older drug called chloroquine, which is used to treat malaria, worked, at least in test tubes. “It functions like a knife that just cuts off the RNA strand,” says Mark Denison, MD, a pediatric infectious disease specialist at Vanderbilt University in Nashville. “They can’t replicate any more. It stops them from doing that.” Denison is part of a team of researchers in Tennessee and North Carolina that discovered remdesivir could stop coronaviruses, like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), in test tubes and animals. He has studied coronaviruses in his lab for 30 years. He knew they would pose a threat again. “We’re shocked, but not surprised, that this has happened again,” he says of the China-based outbreak of 2019-nCoV. After the SARS outbreak, which infected more than 8,000 people in 26 countries in 2002 and 2003, and MERS, which has infected nearly 2,500 people in 27 countries since 2012, researchers knew they had to start looking for treatments that would work against coronaviruses. Denison reached out to Gilead Sciences, a company best known for its antiviral medications that treat HIV and hepatitis C, and asked it to send drug candidates for him to test on coronaviruses. “The idea was that we didn’t want a drug that would just work against SARS or MERS,” he says. “We wanted drugs that worked against every coronavirus.” Many of the agents he tried didn’t work until Denison and his team knocked out the virus’s pesky proofreader. Remdesivir seems to be able to defeat the proofreader, though Denison admits that he does not know how the drug gets around a virus’s defenses. He has a grant from the National Institutes of Health to study that. Gilead has been giving remdesivir to “a small number” of coronavirus patients in the U.S. and Europe on a compassionate basis. One of those patients was a 35-year-old man in Everett, WA, who had gotten pneumonia after being infected with the new coronavirus during a trip to see family in Wuhan, China, the epicenter of the outbreak. His doctors started IV remdesivir on the evening of his seventh day in the hospital. On the eighth day, he improved. He was well enough to stop using oxygen. Signs of pneumonia were gone. He got his appetite back. His case was recently published in The New England Journal of Medicine, igniting a firestorm of interest in the therapy. Unfortunately, though, even Denison says a single person’s case isn’t enough proof that the medication can treat the new coronavirus. The patient, who has not been identified, was getting expert care. He may have improved on his own, despite getting the drug. He says the challenge in people will be to find out two things: whether the medication can block the spread of virus in the body and whether it can reverse the disease. “You can remove the source of injury, but you still have the injury,” he says. Other important questions include how soon the drug may need to be given after infection for it work, and whether it may cause significant side effects. A Promising Pill Another drug, a nucleoside analog, that appears to be able to defeat the coronavirus proofreader, EIDD-2801, was developed by Emory University in Atlanta. It was originally intended to treat the flu but has shown some effectiveness against coronaviruses like SARS and MERS. The FDA recently reached out to Emory asking if it had any drug candidates that might work against the new coronavirus. “It’s a good shot on goal here,” says George Painter, PhD, CEO of Drug Innovation Ventures at Emory (DRIVE) in Atlanta. EIDD-2801 can be taken as a pill, which makes it easier to use outside of a hospital setting. “The capsules for the trial are being made at the end of this month. So we’re close,” Painter says. “ We’re right on the edge.” While these early tests are just getting started, and it will be months until researchers have results, the World Health Organization has sounded a note of caution. In new guidelines for the clinical management of COVID-19, the WHO reminded doctors and patients that there’s not enough evidence to recommend any specific treatment for infected patients. Right now, the guidelines recommend that doctors offer supportive care to help the body fight off an infection on its own. The organization says unlicensed treatments should only be given in the context of clinical trials that have been ethically reviewed, or with strict clinical monitoring in emergencies. Source
