Within a day of testing positive for Covid-19 in June, Miranda Kelly was sick enough to be scared. At 44, with diabetes and high blood pressure, Kelly, a certified nursing assistant, was having trouble breathing, symptoms serious enough to send her to the emergency room.
When her husband, Joe, 46, fell ill with the virus, too, she really got worried, especially about their five teenagers at home: “I thought: ‘I hope to God we don’t wind up on ventilators. We have children. These children will be raised ?'”
. The Kellys, who are from Seattle, agreed to participate in a clinical trial at Fred Hutchinson Cancer Research Center. This is part of an international effort that aims to find an antiviral treatment to stop Covid’s progression.
The couple began taking four pills twice daily the day after their diagnosis. They didn’t know if they were on active medication or placebo but they reported that their symptoms had improved within one week. They were able to recover in two weeks.
” I don’t know if the treatment was given, but it seems like it. Miranda Kelly stated that they felt like the recovery was very quick. “To have all these conditions, I felt like there was a quick recovery The Kellys played a part in the development of what could be the next global strategy to fight Covid. A short-term regimen consisting of daily pills that can combat the virus and prevent the development symptoms after exposure.
“Oral antivirals have the potential to not only curtail the duration of one’s Covid-19 syndrome, but also have the potential to limit transmission to people in your household if you are sick,” said Timothy Sheahan, a virologist at the University of North Carolina-Chapel Hill who has helped pioneer the therapies. Antivirals are essential treatments for viral infections such as HIV and hepatitis C. Tamiflu is the most well-known antiviral. It is a widely used pill that reduces the severity of influenza and can be given promptly.
The medications are designed to prevent and treat viral infections in animals and humans. They can be designed to increase the immune system, fight infection, block receptors to prevent viruses from entering healthy cells and lower the active virus level in the body.
At least three antivirals are currently being tested for Covid in clinical trials. Results can be expected as early as fall or winter according to Carl Dieffenbach (director of the Division of AIDS, National Institute of Allergy and Infectious Diseases), who oversees antiviral research.
” “I believe that we will have answers about what these pills can do within the next few months,” Dieffenbach stated.
The top contender is molnupiravir from Ridgeback Biotherapeutics and Merck & Co., Dieffenbach stated. This product is being tested at the Kellys’ Seattle trial. Two others are a candidate from Pfizer, known as PF-07321332, and AT-527, an antiviral produced by Roche and Atea Pharmaceuticals.
They interfere with the virus’s replication in human cells. Molnupiravir is an example of this. The virus’s replication enzyme makes so many errors that it can’t reproduce. This reduces the patient’s viral load and prevents them from developing a dangerous immune response that could cause severe illness or even death.
To date, only one antiviral drug, Remdesivir, has ever been approved for the treatment of Covid. It is administered intravenously to patients who are sufficiently ill to require hospitalization. However, it is not intended for widespread, early use. The top contenders in the study can be sold as pills.
Sheahan also conducted preclinical research on remdesivir. He led an early experiment in mice which showed that molnupiravir can prevent the early onset of SARS-CoV-2 (the virus that causes Covid). This formula was developed at Emory University and later purchased by Ridgeback and Merck.
Clinical trials have followed, including an early trial of 202 participants last spring that showed that molnupiravir rapidly reduced the levels of infectious virus. Merck Chief Executive Robert Davis said this month that the company expects data from its larger phase 3 trials in the coming weeks, with the potential to seek emergency use authorization from the Food and Drug Administration “before year-end.”
If the results are positive and emergency use is granted for any product, Dieffenbach said, “distribution could begin quickly.”
That would mean millions of people soon could have access to a daily orally administered medication, ideally a single pill, that could be taken for five to 10 days at the first confirmation of Covid infection. Dr. Daniel Griffin from Columbia University, an immunology and infectious disease expert, said that once we get there, that’s what the idea is. “To have this all around the country, so that people get it the same day they get diagnosed.”
Once sidelined for lack of interest, oral antivirals to treat coronavirus infections are now a subject of fierce competition and funding. In June, the Biden administration announced that it had agreed to obtain about 1.7 million treatment courses of Merck’s molnupiravir, at a cost of $1.2 billion, if the product receives emergency authorization or full approval. The same month, the administration said it would invest $3.2 billion in the Antiviral Program for Pandemics, which aims to develop antivirals for the Covid crisis and beyond, Dieffenbach said. Sheahan stated that the pandemic sparked a long-ignored effort to create antiviral therapies for coronaviruses. Although the original SARS virus in 2003 gave scientists a scare — followed by Middle East respiratory syndrome, or MERS, in 2012 — research efforts slowed when the outbreaks didn’t persist. Sheahan stated that the commercial drive to create any products has failed.
A challenge in recruiting participants
Widely available antiviral drugs would join the monoclonal antibody therapies already used to treat and prevent serious illness and hospitalizations caused by Covid. Monoclonal antibodies that mimic the body’s natural response are easier to produce but must be administered intravenous.
The federal government is covering the cost of most monoclonal products at $2,000 a dose. It is still early to determine how antivirals will be priced.
Antiviral pills, Griffin stated, would not be a substitute for vaccination. They could be used as an additional tool in the fight against Covid. He said, “It’s nice having another option.”
Recruiting enough people for clinical trials is a challenge when developing antiviral drugs fast, according to Dr. Elizabeth Duke (Fred Hutch research associate) who oversees the molnupiravir study.
Participants must be unvaccinated and enrolled in the trial within five days of positive Covid tests. Any given day, interns make 100 calls to newly Covid-positive people in the Seattle area — and most say no. “There’s a lot mistrust around the scientific process.” Duke stated. “And some people are saying kinda nasty things to the interns If the antiviral pills work, the next challenge is to set up a distribution system to rush them to patients as soon as they become positive. Griffin said it will take something akin to the program set up last year by UnitedHealthcare, which sped Tamiflu kits to 200,000 at-risk patients enrolled in the insurer’s Medicare Advantage plans.
Merck officials predicted that the company could produce more than 10 million courses of therapy by the end of the year. Similar estimates have not been released by Pfizer and Atea.
Even more promising? Studies to determine if antivirals can prevent infection following exposure.
“Think of that,” Duke said. He is also leading a prophylactic study. It could be given to all members of a household, or even everyone at school. Then we’re talking about a return to, maybe, normal life.”