How do you treat an illness like COVID-19 for which there are no FDA-approved treatments? Capitalize on research on other viruses, experts told 鶹ý.
Unlike influenza and other viruses, nothing is approved specifically to treat COVID-19, although that hasn't stopped clinicians in China and around the world from trying different therapies.
Warner Greene, MD, PhD, of University of California San Francisco (UCSF) and director of the Center for HIV Cure Research at Gladstone Institutes, told 鶹ý that researchers ideally should be developing therapies to treat SARS-CoV2 coronavirus at all stages of its life cycle.
"Introducing one drug at a time is a recipe for resistance, like we saw in HIV," he said. "We don't have the luxury of four different antivirals against coronavirus, and hopefully we don't have to deal with [resistance] down the road."
Remdesivir, an investigational therapy developed by Gilead Sciences specifically to treat Ebola, has been the highest-profile candidate so far. Two clinical trials of the therapy are currently ongoing in China, and on Tuesday, the National Institute of Allergy and Infectious Diseases announced involving the drug.
Hospitalized adults diagnosed with COVID-19 (diagnosed SARS-CoV2 infection with lung involvement) will be eligible to participate. Participants will provide blood samples and nose and throat swabs, and outcomes from the intervention and control groups will be compared on day 15 to determine clinical benefit.
Already one patient has been enrolled: an American recently repatriated from the Diamond Princess cruise ship.
Greene explained that remdesivir works by targeting a viral RNA polymerase.
"They tried to do it in Ebola and it didn't work there. Maybe it will work on this RNA polymerase," he said.
CNN reported a World Health Organization official recently said that against coronavirus, though with clinical trials just getting underway, the basis for his optimism was unclear.
Another drug under investigation to treat COVID-19 is lopinavir/ritonavir (Kaletra), a protease inhibitor combination used to treat HIV. Doctors in Thailand said it showed efficacy against patients with severe coronavirus. That led to a run on the drug in China, anecdotal reports indicated, such that Chinese HIV patients were unable to obtain it.
"If [lopinavir/ritonavir] works, it would do so by cross-reacting and inhibiting one of the [SARS-CoV2] proteases present," Greene said.
But he described such a situation as "very lucky" as "these drugs are like lock-and-key" in terms of treating viruses.
"It would be unexpected the key to one house would open the door to another house, but it might," Greene explained.
Peter Hunt, MD, also of UCSF, told 鶹ý that this isn't the first time lopinavir/ritonavir has been tried in coronavirus outbreaks.
"[The drug] has been tested in animal models of SARS and MERS, and with conflicting data. It was given to people with SARS with reported improved responses compared to historical controls, but the study design made it impossible to tell if this was a real effect," he said.
At a Department of Health and Human Services (HHS) briefing on Tuesday, officials said they have received "hundreds of proposals for therapeutics," including from Janssen and Regeneron. Recently, HHS announced it will to develop treatments for coronavirus infection, with the company identifying compounds that have antiviral activity against SARS-CoV2.
Regeneron developed a monoclonal antibody therapy that showed efficacy against Ebola in the same trial that tested remdesivir in these patients.
And because it worked in Ebola, using "convalescent serum" from patients who recovered from the disease could work against COVID-19, Greene said.
"Monoclonal antibodies in Ebola, particularly if you catch it early, can get amazing clinical responses. There's lots of reason to hope," he noted.
Successful treatment strategies in Ebola have involved a ring vaccination strategy of protection around people getting treated with monoclonal antibodies, Greene said.
Obviously, that depends on getting a viable SARS-CoV2 vaccine. But he added that he doesn't foresee the same challenges seen with HIV because coronavirus "doesn't attack CD4 T-cells, it doesn't take out the immune system like HIV does."
"The blueprint is there, it's a matter of executing on the blueprint," Greene said.