CLEVELAND, Ohio (Tribune News Service) — When people come down with a mild case of COVID-19, there's no drug treatment for home use to stop it from getting worse.

By next year, a person who just tested positive for COVID-19 could phone their doctor and ask for a prescription pill or nasal spray to stop the viral infection.

Pharmaceutical companies are in a race to find at-home COVID-19 treatments that could save lives, reduce hospitalizations and hasten the return to normalcy in the United States.

The answer could be nanoparticles that are tinier than cells, antiviral drugs that short-circuit how viruses replicate, combinations of drugs, or existing drugs repurposed to fight COVID-19.

Pfizer has said its experimental drug could be here by the end of the year. Other therapeutics, developed by various companies, are in early clinical trials.

The hunt for new drugs is urgent, said Dr. Rajesh Gandhi, professor of medicine at the Harvard Medical School.

"We need better drugs to keep people out of the hospital, (and) we need better drugs to treat people once they're in the hospital," Gandhi said during a recent webinar sponsored by the Infectious Diseases Society of America. "The time to develop (those drugs) is right now, because of continued outbreaks around the world."

COVID-19 prescription drugs could help prevent or decrease the probability of those exposed to COVID-19 catching the illness.

These drugs also could help those who don't get as much protection from vaccines, such as older people and those with weakened immune systems, said Dr. Grace McComsey, vice president of research at University Hospitals and lead investigator of a COVID-19 drug trial based at UH.

"We're still going to see some COVID cases" in those populations, McComsey said. "You want to be able to treat those people before they get worse, not wait for them to get to the hospital. It may be too late by then."

Currently available COVID-19 treatments include monoclonal antibodies, made in labs by cloning a white blood cell, and the drug remdesivir. Drugs such as dexamethasone, tocilizumab and baricitinib are also been effective in patients with severe COVID-19, Bhirmaj said.

Monoclonal antibodies and remdesivir are administered intravenously in a hospital or clinic. They aren't appropriate for people who test positive for the virus and want a prescription drug they can take at home.

"We cannot have just a few things that are for late, late course, when people are really sick," McComsey said. "We need something to prevent (disease) progression so that people can stay home, take a pill and not come to the hospital."

The medical community put a lot of effort into developing vaccines, but the search for cheaper, easy-to-manufacture drugs that stop COVID-19 infections early, or even prevent the infection, is also vital, said Dr. Adarsh Bhimraj, a staff physician in the Department of Infectious Disease at the Cleveland Clinic, and chair for the infectious Diseases Society of America COVID-19 treatment guideline panel. He spoke during the Infectious Diseases Society of America webinar about COVID-19 treatments.

"Imagine having a pill which doesn't require any cold storage; anybody can take it from Sub-Saharan Africa to Antartica," Bhimraj said. "I think that'll be so much more effective."

Here are some of the most promising COVID-19 treatments, when they will be available and who they might help.

Nanoparticles

How they work: When injected into the body, nanoparticles — which are smaller than cells — bind to the virus, then move it away from other cells. Nanoparticles then target the virus for destruction by the immune system.

"It uses your own body to fight the infection for you," explained Jillian Rosenberg, a post-doctoratoral researcher at the University of Chicago. She was part of a team investigating a proposed nanoparticle COVID-19 treatment; its research was recently published in the journal Matter.

These nanoparticles could be administered as a nasal spray sold in drug stores for people who are in the early stages of the illness. The drug could be reformulated for severe hospitalized cases, or against COVID-19 variants, researchers said.

When could this help patients?

The University of Chicago team tested a nanoparticle COVID-19 treatment in a pair of donated lungs kept alive on a ventilator, but the team does not have the safety facilities needed to conduct the next experiments.

"We hope that a pharmaceutical company would like to license our technology to conduct the clinical trials that we don't have the capacity to do," Rosenberg said.

Protease Inhibitors

How they work: These antiviral drugs, currently used for treating HIV and other viral infections, work by inhibiting a crucial enzyme inside virus cells. Inhibiting the enzymes can help stop viruses from entering cells and replicating, thus helping to stop infections.

When could this help patients?

Pfizer is conducting a Phase 1 study In the United States of an investigational, novel protease inhibitor for COVID-19. The drug may be useful to treat COVID-19 and future coronaviruses, the company said.

Because the drug is still in research and development, Pfizer said in a statement that it could not speculate on when it might be available for patients.

Pfizer CEO Albert Bourla was more optimistic when he appeared on CNBC in April. If clinical trials go well and the proposed drug is approved by the Food and Drug Administration, it could be available for U.S. distribution by the end of the year, Bourla said.

RedHill Biopharma is testing two investigational oral pills to treat COVID-19. One is opaganib, which is being studied in hospitalized patients, and one is RHB-107 (upamostat), a protease inhibitor being studied for at-home use.

The drug aimed at mild to moderate cases, upamostat, is an investigational protease inhibitor that's taken once daily for two weeks and is expected to be effective against coronavirus variants.

Both opagnib and upamostat may, if approved for use, be used as treatment both inside and outside of hospitals, the company said.

RedHill is currently conducting a phase 2/3 study of upamostat in the United States. "We're targeting patients who were very early in the course of the illness, the first few days," said RedHill medical director Dr. Terry Plasse.

UH is among the sites in the upamostat trials, and is still enrolling participants. For more information about the study, please see uhhospitals.org/upamostat or call 1-833-788-7425.

What is slowing the search for COVID-19 medicines?

The Clinic's Bhimraj is optimistic that better drug therapies for COVID-19 will be discovered. But he doubts that a magic bullet for the illness — like penicillin for bacterial infections — will be found. Medicine still doesn't have effective drugs to treat most respiratory viruses, he said in a follow-up email.

"I think combinations of different treatments will be more effective" in treating COVID-19, Bhimraj said. "What is also important is not just studying new drugs and combinations of drugs, but also exploring which drugs work best in which specific scenarios, such as specific times in the disease course (early or late), in which level of disease severity (mild-moderate, severe, critical) and what kind of patients (older age, with cardiovascular co-morbidities, obesity, etc.)."

Developing a vaccine is faster and easier than finding a therapeutic drug, said RedHill chief operating officer Gilead Raday. Vaccines are easier to test and evaluate, because trial participants either get COVID-19 or they don't, Raday said.

In drug trials, "you have to select what level of disease and what stage of disease you are actually benefiting, and then you need to make sure that patients (in the trial) are only those that are at that stage of the disease," Raday said. "The mechanism of how the disease develops is more complex than just being infected or not being infected."

As drug trials continue, researchers will gain a better understanding of which drugs, or drug combinations, are most effective.

"We have made phenomenal progress in terms of what does and doesn't work, but we need to continue that momentum, because we're not where we need to be with treatment yet," Harvard's Gandhi said.

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