On Friday, the World Health Organization (WHO) announced a large global trial, called SOLIDARITY, to find out whether any can treat infections with the new coronavirus for the dangerous respiratory disease. It’s an unprecedented effort—an all-out, coordinated push to collect robust scientific data rapidly during a pandemic.
The study, which could include many thousands of patients in dozens of countries, has been designed to be as simple as possible so that even hospitals overwhelmed by an onslaught of COVID-19 patients can participate.
Drugs that slow or kill the novel coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), could save the lives of severely ill patients, but might also be given to protect health care workers and others at high risk of infection.
Treatments may also reduce the time patients spend in intensive care units, freeing critical hospital beds.
Remdesivir
Originally developed by Gilead Sciences to combat Ebola and related viruses, remdesivir shuts down viral replication by inhibiting a key viral enzyme.
Researchers tested remdesivir last year during the Ebola outbreak in the Democratic Republic of the Congo, along with three other treatments. It did not show any effect. (Two others did.) But the enzyme it targets is similar in other viruses, and in 2017 researchers at the University of North Carolina, Chapel Hill showed in a test tube and animal studies that the drug can inhibit the coronaviruses that cause SARS and MERS.
The first COVID-19 patient diagnosed in the United States—a young man in Snohomish County in Washington—was given remdesivir when his condition worsened; he improved the next day, according to a case report in The New England Journal of Medicine (NEJM). A Californian patient who received remdesivir—and who doctors thought might not survive—recovered as well.
Such evidence from individual cases doesn’t prove a drug is safe and effective but from all the drugs in the SOLIDARITY trial, “remdesivir has the best potential to be used in clinics” says Jiang Shibo of Fudan University, who has long worked on coronavirus therapeutics. Jiang particularly likes that high doses of the drug can likely be given without causing toxicities.
Chloroquine and hydroxychloroquine
At a press conference on Friday, President Donald Trump called chloroquine and hydroxychloroquine a “game-changer.” “I feel good about it,” Trump said. His remarks have led to a rush in demand for the decades-old antimalarials.
The WHO scientific panel designing SOLIDARITY had originally decided to leave the duo out of the trial, but had a change of heart at a meeting in Geneva on 13 March, because the drugs “received significant attention” in many countries, according to the report of a WHO working group that looked into the drugs’ potential. The widespread interest prompted “the need to examine emerging evidence to inform a decision on its potential role.”
Studies in cell culture have suggested chloroquines have some activity against SARS-CoV-2, but the doses needed are usually high—and could cause serious toxicities.
Researchers in France have published a study in which they treated 20 COVID-19 patients with hydroxychloroquine. They concluded that the drug significantly reduced viral load in nasal swabs.
Ritonavir/lopinavir
This combination drug, sold under the brand name Kaletra, was approved in the United States in 2000 to treat HIV infections. Abbott Laboratories developed lopinavir specifically to inhibit the protease of HIV, an important enzyme that cleaves a long protein chain into peptides during the assembly of new viruses. Because lopinavir is quickly broken down in the human body by our own proteases, it is given with low levels of ritonavir, another protease inhibitor, that lets lopinavir persist longer.
The combination can inhibit the protease of other viruses as well, specifically coronaviruses. It has shown efficacy in marmosets infected with the MERS virus and has also been tested in SARS and MERS patients, though results from those trials are ambiguous.
Ritonavir/lopinavir and interferon-beta
SOLIDARITY will also have an arm that combines the two antivirals with interferon-beta, a molecule involved in regulating inflammation in the body that has also shown an effect in marmosets infected with MERS. A combination of the three drugs is now being tested in MERS patients in Saudi Arabia in the first randomized controlled trial for that disease.
But the use of interferon-beta on patients with severe COVID-19 might be risky, Herold says. “If it is given late in the disease it could easily lead to worse tissue damage instead of helping patients,” she cautions.
This article originally appeared on Science Magazine by Kai Kupferschmidt and Jon Cohen. Read the full article here.