- Treatment for people who have contracted SARS-CoV-2 has come a long way in the past 12 months, but new medications are still needed.
- The oral antiviral MK-4482 effectively reduced the impact on the lungs of SARS-CoV-2 infections in a very small trial in hamsters.
- With human trials ongoing, the research raises hope for an effective, easy-to-take COVID-19 medication.
While vaccinations reduce the incidence of SARS-CoV-2 infections, there is still a need for drugs that can treat people who have contracted the virus.
The National Institutes of Health (NIH) have recommended two drugs to treat COVID-19: the steroid dexamethasone and the antiviral drug Remdesivir.
Doctors limit the use of dexamethasone to severe disease, where trials have shown it to reduce mortality in mechanically ventilated patients by a third.
Remdesivir can decrease the length of time a person has COVID-19 and does provide some benefit to some people, but it has little effect on its own. Remdesivir also requires intravenous administration, which lessens its clinical use.
Researchers with the NIH have found that the oral antiviral drug MK-4482 effectively fights SARS-CoV-2 infections in hamsters.
MK-4482, which scientists are now testing in human clinical trials, reduced the level of SARS-CoV-2 replication and disease damage in the lungs of hamsters. The researchers administered MK-4482 orally.
If trials can confirm the therapeutic value of MK-4482 in humans, it will be the first drug for SARS-CoV-2 that people can take orally in the community.
The research appears in the journal nature communications.
Scientists initially developed MK-4482 as an anti-influenza drug by the Drug Innovation Ventures group of Emory University in Atlanta, GA, with funding support from the National Institute of Allergy and Infectious Diseases. The original names for MK-4482 were molnupiravir and EIDD-2801.
When scientists hydrolyze MK-4482, the resulting compound is EIDD-1931, originally developed at the beginning of this century for treating hepatitis C.
The compound shows promise for stopping MERS-CoV and SARS-CoV-1 in epithelial cells in vitro and in mouse models.
Merck and Ridgeback Biotherapeutics are currently conducting Phase 2 and 3 human clinical trials of MK-4482 as a SARS-CoV-2 treatment.
Rocky Mountain Laboratories, which is a branch of NIH’s National Institute of Allergy and Infectious Diseases in Hamilton, Montana, conducted the study of MK-4482 in hamsters. Researchers there collaborated with scientists at the University of Plymouth in the United Kingdom.
Last year, the researchers developed the model for emulating human SARS-CoV-2 infections and mild cases of COVID-19 in golden Syrian hamsters. The team determined the dosing of MK-4482 for the hamsters based on its previous successful use in stopping SARS-CoV-1 and MERS-CoV.
In the current study, the researchers tested the effects of MK-4482 using three hamster groups, allocating six hamsters to each group. The researchers gave the drug to the first group of hamsters at 12 hours and 2 hours before infecting them with SARS-COV-2. The second group received MK-4482 12 hours after infection.
The researchers gave MK-4482 to the hamsters in both these groups every 12 hours for 3 days.
Researchers infected the third — control — group with the virus but did not treat them with MK-4482.
When the trial concluded, the researchers found that the animals who had received the drug had 100 times lower levels of infectious SARS-CoV-2 in their lungs than the untreated group.
These hamsters had also developed significantly fewer lesions in lung tissue than their untreated counterparts.
The authors of the research note that after they submitted their work for publication, a second study reporting MK-4482’s effectiveness for treating SARS-CoV-2 was released.
While the two studies differ in some details, “both studies support a significant effect of MK-4482 pre-treatment on SARS-CoV-2 replication in the lung, both in terms of viral RNA and virus titer [virus load], which was also reflected in decreased lung pathology.”
If MK-4482 proves as successful in ongoing human clinical trials as it has been for hamsters, it would be an easy-to-take, oral medication for those who have contracted SARS-CoV-2 and those who have developed symptoms of COVID-19.
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