New combination of drugs may help treat COVID-19

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A recent study tests combinations of drugs for the treatment of COVID-19. Himanshu Vyas/Hindustan Times via Getty Images
  • Although vaccines are now available for most of the world, a more successful treatment for COVID-19 is still necessary.
  • Researchers believe that a combination of Food and Drug Administration (FDA)-approved antiviral medications could help people with SARS-CoV-2 infections.
  • They combined the drug remdesivir, which is effective against Ebola, with drugs that can treat hepatitis C.

With worldwide COVID-19 cases on the rise again, the race to find an effective treatment for the disease continues.

Researchers from Mount Sinai Hospital in New York City, NY, believe that a combination of drugs already approved for use in the United States could be the key in treating COVID-19.

The researchers combined remdesivir, which doctors already prescribe to hospitalized patients with COVID-19, with different hepatitis C virus (HCV) medications. They hoped to identify a combination that slows viral replication.

“Here we see a promising synergy that, if confirmed through additional research and clinical trials, could provide a new antiviral to combat COVID-19,” says Dr. Gaetano Montelione, Ph.D., a professor at Rensselaer Polytechnic Institute in Troy, NY.

Since the World Health Organization (WHO) declared the novel coronavirus a pandemic in March 2020, nearly 150 million people have contracted the virus, and approximately 3 million have died.

Over the past year, researchers have investigated numerous drugs and therapies to help treat COVID-19.

Remdesivir, for example, can treat COVID-19 in an inpatient setting. According to one article, remdesivir can “target specific viral enzymes or attack a weak point of viral replication within the host.”

Certain corticosteroids, such as dexamethasone, can reduce inflammation in people with COVID-19.

Researchers also considered using hydroxychloroquine to treat COVID-19. Doctors use hydroxychloroquine to treat malaria and rheumatoid arthritis, but further research showed that it did more harm than good in people with COVID-19.

The authors of the recent paper, which appears as a pre-proof in the journal Cell Reports, considered 10 different HCV drugs in their study. Their goal was to find something that amplified the effects of remdesivir in people with COVID-19.

The research team thought that the HCV drugs could bind to an enzyme called Mpro. This enzyme is SARS-CoV-2’s main protease, which is essential for viral replication.

The team tested the HCV drugs in monkey and human cells. They found that 7 of the 10 drugs could act as a SARS-CoV-2 inhibitor.

Although seven drugs were effective at inhibiting replication of the virus, further experiments showed that four of them inhibited a different protease called PLpro.

The four drugs that were effective at boosting the benefits of remdesivir were paritaprevir, grazoprevir, simeprevir, and vaniprevir.

Those drugs synergized with remdesivir. This means that they increased remdesivir’s effectiveness at reducing viral replication by “as much as 10-fold.”

“Combined use of remdesivir with PLpro inhibitors for the treatment of COVID-19 could be a game changer for [people] with COVID-19 who are not vaccinated,” says study author Dr. Adolfo Garcia-Sastre.

Dr. Kris White, an assistant professor of microbiology at Icahn Mount Sinai in New York City, NY, believes that the new research could “produce a highly effective antiviral cocktail.”

Chris Coleman, an assistant professor of infection immunology at the University of Nottingham in the United Kingdom, told Medical News Today that this research has “multiple positive aspects.”

“Targeting two steps of the viral replication means you hit the virus twice, making it less likely that the virus will mutate to escape the treatment,” he explained.

Although the combination has much potential, researchers say that there is one major roadblock to overcome: Remdesivir is not an oral drug. People receive it intravenously in a hospital setting, so a doctor would not be able to simply write a prescription and send a person home for treatment.

It can take 30 minutes to 2 hours to inject remdesivir. Additionally, people typically receive it daily, and treatment can last for 5–10 days.

Administering the medication only in a hospital setting poses a number of problems. Not only would it be less than ideal for people who are ill to travel to receive treatment, but it would also be less accessible due to cost and travel constraints.

“Our goal is to develop a combination of oral drugs that can be administered to outpatients before they are sick enough to require hospitalization,” says co-corresponding study author Dr. Robert M. Krug.

Dr. Jonathan Stoye, a virologist at the Francis Crick Institute in London, U.K., told MNT that he finds the results promising but that more work is necessary.

“This interesting study seeks to identify novel strategies for the therapy of COVID-19 using combinations of FDA-approved, repurposed drugs originally developed against other viruses,” said Dr. Stoye.

“It clearly demonstrates that drugs targeting the protease of HCV in combination [with] remdesivir show synergistic inhibition of SARS-CoV-2 replication.”

“However, although these results are promising, they seem rather preliminary since the mechanism by which the drugs synergize is not established. In particular, the true target(s) of the protease inhibitors remains poorly defined.”

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