- A study in mice found that molnupiravir (EIDD-2801) halted the replication of SARS-CoV-2 — the virus that causes COVID-19 — in grafts of human lung tissue.
- The drug also prevented infection when administered 12 hours before exposure to the virus.
- Clinical trials of the drug are ongoing to evaluate its safety in humans and whether it can make patients with COVID-19 less infectious.
- Previous research suggests that the drug could work against a range of coronaviruses that originate in bats, providing protection in future outbreaks.
A drug called molnupiravir, which scientists originally developed to treat influenza, is showing promise as a treatment for COVID-19.
A study by researchers at the University of North Carolina (UNC) at Chapel Hill, recently published in Nature, found that the drug dramatically reduced the number of virus particles in a mouse model of the disease.
It also protected against infection when given 12 hours before exposure to the virus and every 12 hours thereafter.
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Phase 2 and phase 3 clinical trials of molnupiravir are already under way, with some results expected as soon as March 2021.
In addition to testing the drug’s safety and efficacy, one of the trials is also investigating its effect on “viral shedding,” which is the amount of virus released into the environment by people who have it. Analyzing this helps determine how likely a person is to transmit the virus.
Remdesivir, which speeds the recovery of adults hospitalized with the illness and which may reduce mortality rates, is currently the only proven antiviral treatment for COVID-19.
One potential advantage of molnupiravir is that patients can take it orally, whereas remdesivir has to be injected. This would make molnupiravir easier to give to lots of people as a preventive, or prophylactic, drug in high risk settings, such as nursing homes and long-term care facilities.
Another, more long-term benefit of molnupiravir is that it may be effective against other emerging coronavirus infections that — like SARS-CoV-2 — probably originate in bats.
A new animal model of COVID-19
To test the efficacy of molnupiravir against SARS-CoV-2, the researchers created a completely new model of COVID-19 in mice that may prove useful for testing the efficacy of other antiviral drugs.
Human coronaviruses are unable to infect mouse cells unless researchers either adapt the viruses or genetically modify mice to produce receptors that allow them to invade cells.
These models also fail to reflect the diversity of cells found in human lungs, where the infection can cause life threatening damage.
To get around these limitations, the researchers implanted human lung tissue into specially bred immunodeficient mice that tolerate foreign tissue.
“Virus replication in this model occurs in bona fide human lung tissue and does not require any type of adaptation of the virus or the host,” the researchers write in their paper.
They demonstrated that the newly emerged human coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2 were all able to replicate in the implanted human lung tissue.
“Our model allows researchers to directly compare infection between human coronaviruses and the effectiveness of potential preventative and therapeutic approaches,” says co-first author Dr. Lisa Gralinski, assistant professor of epidemiology at UNC.
When infected with SARS-CoV-2, the human lung tissue sustained damage similar to that seen in the lungs of COVID-19 patients. The infection also induced an inflammatory response reminiscent of the excess inflammation that characterizes the disease in people.
“Remarkable” effect of treatment
Next, the researchers treated the mice with molnupiravir, starting either 24 or 48 hours after they were exposed to SARS-CoV-2.
“We found that [molnupiravir] had a remarkable effect on virus replication after only 2 days of treatment — a dramatic, more than 25,000-fold reduction in the number of infectious particles in human lung tissue when treatment was initiated 24 hours post-exposure,” said senior author Dr. J. Victor Garcia-Martinez, professor of medicine and director of the International Center for the Advancement of Translational Science at UNC.
When the treatment was started 48 hours after exposure to the virus, the concentration of virus particles fell by 96%.
Finally, the researchers tested the ability of molnupiravir to prevent infection.
When they gave the drug to mice 12 hours before exposure to SARS-CoV-2, and every 12 hours afterward, it reduced the concentration of virus particles by over 100,000-fold compared with untreated mice.
In previous lab-based studies by the same group, the drug showed promise against two other newly emerged coronaviruses that may have originated in bats: SARS-CoV, which causes SARS, and MERS-CoV, which causes MERS.
This suggests that molnupiravir could protect against a range of bat coronaviruses that make the leap into humans.
“Overall, these results indicate that EIDD-2801 may not only be efficacious in treating and preventing COVID-19, it could also prove to be highly effective against future coronavirus outbreaks as well,” said co-author Dr. Ralph Baric, the William Kenan Distinguished Professor of Epidemiology at the UNC Gillings School of Global Public Health and the UNC School of Medicine.
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