On Monday, a team of researchers at UNC-Chapel Hill, in conjunction with colleagues at Vanderbilt University, Emory University, and the Centers for Disease Control and Prevention, announced a potential breakthrough in the fight against COVID-19. 

In a paper published on the biology preprint server bioRxiv in March, the researchers—co-led by UNC-Chapel Hill epidemiologist Timothy Sheahan—said their research showed that

“ribonucleoside analog β-D-N4-hydroxycytidine (NHC, EIDD-1931) has broad spectrum antiviral activity against SARS-CoV 2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c Bat-CoVs, as well as increased potency against a coronavirus bearing resistance mutations to another nucleoside analog inhibitor. In mice infected with SARS-CoV or MERS-CoV, both prophylactic and therapeutic administration of EIDD-2801, an orally bioavailable NHC-prodrug (b-D-N4-hydroxycytidine-5’-isopropyl ester), improved pulmonary function, and reduced virus titer and body weight loss. Decreased MERS-CoV yields in vitro and in vivo were associated with increased transition mutation frequency in viral but not host cell RNA, supporting a mechanism of lethal mutagenesis. The potency of NHC/EIDD-2801 against multiple coronaviruses, its therapeutic efficacy, and oral bioavailability in vivo, all highlight its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic coronaviruses.”

In other words, writes Michael Waldholz for Scientific American, “An oral medicine was able to hinder the coronavirus behind COVID-19 as it attempted to replicate itself in human lung cells in test tubes.  … It also hampered closely related coronaviruses from reproducing in mice for several days and improved their lung functions. The drug, called EIDD-2801, interferes with a key mechanism that allows the SARS-CoV-2 virus [i.e., the novel coronavirus] to reproduce in high numbers and cause infections.”

The paper has yet to undergo peer-review, which means there might be undiscovered flaws that undercut the findings. The medicine, EIDD-2801, still needs to be tested on humans. But if it performs in human trials as it has both in animals and in test tubes—and if there are no dangerous side effects—it might be a game-changing treatment for not just COVID-19 but other diseases caused by closely related coronaviruses. (And it likely has more scientific weight behind it than the hydroxychloroquine President Trump began hyping after conversations with Laura Ingraham, Rudy Giuliani, and Dr. Oz.)  

A Miami-based company called Ridgeback Biotherapeutics has licensed the drug and received permission from the Food and Drug Administration to begin patient trials of EIDD-2801 in the next few months. 

These same universities collaborated on an earlier study that found that the drug remdesivir stopped the coronaviruses that caused the SARS and MERS outbreaks from replicating. That drug is now in clinical trials—including at Duke Health—and results may come by the end of the month, according to Waldholz. 

“EIDD-2801 inhibits the coronavirus’s self-copying operations in a manner that is different from remdesivir,” Waldholz explains. “While remdesivir brings that replication process to a full stop, EIDD-2801 introduces mutations—mistakes—into the virus’s RNA as it makes copies so that the viral RNA becomes so damaged that it cannot infect cells. Another feature of the drug is that it is able to work against a host of other RNA viruses. Thus, it could serve as a multipurpose antiviral, much in the way some antibiotics can work against a wide variety of bacteria.” 

It could also potentially be used as a prophylactic or “to protect uninfected nursing home residents and workers if an outbreak occurs inside a facility.” Ridgeback Biotherapeutics cofounder Wayne Holman told Waldholz that he envisions people in the early days of COVID-19 taking EIDD-2081 to “prevent it from progressing to hospitalization, mechanical ventilation, or death.”

Contact editor in chief Jeffrey C. Billman at jbillman@indyweek.com. 

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