Teaching ‘old drugs new tricks’: Experts rush to identify therapeutics for COVID-19
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The COVID-19 pandemic has left academic institutions, government bodies and the private sector scrambling to find drugs to combat the novel coronavirus.
Physicians have repurposed drugs for other diseases to treat seriously ill patients, such as the antimalarial medication chloroquine and remdesivir, an antiviral developed for Ebola.
“We’re basically trying to teach an old drug new tricks,” said Infectious Disease News Editorial Board Member Peter Chin-Hong, MD, professor of medicine and director of the transplant infectious disease program at the University of California, San Francisco.
“In general, ID physicians work closely with ID pharmacists. They’ve been rising to the occasion and helping us a lot with therapeutic options, because we can’t keep up,” he said. “Everything is changing by the hour.”
In the rush to find an effective treatment, Gilead Sciences announced that it would no longer accept new compassionate use requests for remdesivir because of a surge in demand from physicians looking to use the drug as a potential therapy for COVID-19. Other institutions are exploring alternative treatments for COVID-19, such as AlloVir’s and Baylor College of Medicine’s efforts to develop T-cell therapy for the virus.
Infectious Disease News Editorial Board Member Kathleen M. Neuzil, MD, MPH, FIDSA, professor of vaccinology and director of the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine, said a lack of lab researchers with expertise in coronaviruses also has been an obstacle.
“We had very few bonafide coronavirus laboratory research experts before this pandemic hit,” Neuzil said. “It just wasn’t a well-funded area.”
Another barrier is the rapid pace at which the virus makes people ill, she continued.
“One issue with drugs, and particularly drugs for viral infections, is that they usually work better early in the illness,” said Neuzil. “If we’re not catching people and diagnosing them early enough, then it may look like the drug doesn’t work, when in reality we just gave it to them too late.”
Neuzil also emphasized that collaboration between institutions, the government and private sectors is “absolutely critical” in expediting drug development. Some organizations, including the American Society for Microbiology (ASM), have held online panels and meetings to increase the pace of research.
“As the NIH Director Francis Collins said, the only thing more contagious than the virus itself is actually help. To me, scientists are truly factories of hope, because science is help,” Stefano Bertuzzi, PhD, MPH, CEO of ASM, said during an online session. “ASM has been assisting from the very beginning. We’re ramping up to facilitate coordination and cooperation among microbiologists from around the world.”
During the session, Vineet Menachery, PhD, assistant professor of microbiology and immunology at the University of Texas Medical Branch, discussed therapeutics being assessed for COVID-19, noting that options for coronaviruses have been — and remain — limited.
“While groups have spent several years trying to come up with coronavirus treatments since the emergence of SARS), there haven’t been many successful efforts until very recently,” he said.
According to Menachery, remdesivir demonstrated efficacy in animal trials and against both SARS and MERS. He added that there have also been published reports of the drug’s efficacy in larger animals as well as additional data from humans in Ebola trials, making it “probably the best” and “most promising” therapeutic option at this time.
The problem, however, is that remdesivir is an IV drug, meaning patients must be in a hospital setting to receive it. This makes it an option only for people with severe cases of COVID-19, according to Menachary.
Other options being considered include hydroxychloroquine and chloroquine, as well as monoclonal antibodies.
According to Menachary, the panel spent significant time talking about convalescent sera — a “very old technique” that uses the immunity generated from people who have recovered and developed immunity to the illness.
“The thought is that convalescent sera can protect against this virus,” Menachary explained. “The timing and the kinetics and the sheer amount of sera that would be required will be the main barriers. But it is being pursued by many groups, primarily the group at Johns Hopkins.”
He added: “There will be a number of groups that will be testing viruses from all around the world, using FDA compounds and other libraries, looking for things that can disrupt the infection. We’re just starting to search for compounds that may already be approved for human use that can be rapidly sent into the field to be tried.”
David E. Gordon, PhD, associate researcher of cellular molecular pharmacology at the UCSF School of Medicine, and colleagues are testing existing compounds and drugs for efficacy against COVID-19. In a recent paper, Gordon outlined how he and fellow researchers cloned, tagged and expressed 26 of 29 viral proteins in human cells and identified the human proteins physically associated with each. This process identified 332 high-confidence SARS-CoV-2 human protein-protein interactions.
Gordon and colleagues were able to identify 67 druggable human proteins or host factors targeted by 69 FDA-approved drugs and drugs in clinical trials and/or preclinical compounds. The researchers are now evaluating these agents in live SARS-CoV-2 infection assays.
Infectious Diseases Society of America President and Infectious Disease News Editorial Board Member Thomas File Jr., MD, MSc, FIDSA, saidthat confounding circumstances, like patients being enrolled into trials for two different COVID-19 drugs, may be an issue once drugs like remdesivir move to clinical trials.
“One of the challenges is that a lot of people are going to be put on hydroxychloroquine and then they may be entered into the remdesivir trial. Is that going to confound the results?” File said. “If hydroxychloroquine indeed has some benefit or effect, and then you put them in another study, that may confound the ability to actually assess the true benefit of one drug vs. the contributed effect of this other drug.”
Despite these challenges, File noted it may be easier to obtain consent for COVID-19 drug trials due to public interest in finding effective therapies.
According to Chin-Hong, academic institutions can be “very nimble” compared with private sector research bodies because of a lack of economic incentive and fear of “detriment to shareholders” when developing new drugs in a pandemic environment.
“Institutions all around the country transformed themselves to focus solely on COVID-19,” Chin-Hong said. “It’s amazing that these billion-dollar institutions can do that very quickly, not only from a clinical care perspective, but — for a group like the one at UCSF — from a repurposing/evaluating drugs perspective.”
“I think this is different because people are personally at risk,” Chin-Hong added. “This is at your front door.” – by Eamon Dreisbach and Caitlyn Stulpin
- Reference:
- CDC. Coronavirus disease 2019 (COVID-19). https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/cases-in-us.html. Accessed March 25, 2020.
- Gordon DE, et al. bioRXiv. 2020; doi:10.1101/2020.03.22.002386.
- WHO. Coronavirus disease 2019 (COVID-19) situation report – 64. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200324-sitrep-64-covid-19.pdf?sfvrsn=723b221e_2. Accessed March 25, 2020.
Disclosures: Chin-Hong, File and Neuzil report no relevant financial disclosures.
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