As the US government pumps billions of dollars into COVID-19 antiviral research, scientists are racing to develop a drug that people can take at home to treat the disease in its early stages. If last year’s focus was on reusing existing drugs to target COVID-19 while developing a vaccine, much of this year’s research must be focused on producing new antiviral drugs to help treat those who get it. While many people are legitimately concerned with vaccines to help prevent hospitalization and death, they are only one part of the “Arsenal” necessary to fight this novel coronavirus.
Not everyone can or will be vaccinated. For some people, such as those with weakened immune systems, the vaccine is not particularly effective. And, despite our best efforts, vaccines will never be 100 percent effective in stopping transmission or infection. Right now, the COVID-19 vaccine is a powerful tool to help save lives. They incontestably break the link between infection, hospitalization and death, turning a serious, deadly disease into something more manageable.
A $3 billion project
In June, the U.S. government launched a new initiative called the Pandemic Antiviral Initiative (APP), which will invest more than $3 billion to develop antiviral drugs to treat COVID-19. As Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases (NIAID), explains, the goal of the APP is to develop oral antiviral drugs that can be taken at home soon after symptoms appear.
“I wake up in the morning and I don’t feel great, my sense of smell and taste is gone, I have a sore throat,” Fauci explained. I called my doctor and I said, ‘I have COVID and I need a prescription. ‘”
Antiviral drug design is not easy
Currently, treatments for patients with COVID-19 are relatively limited. A new antibody treatment made by pharmaceutical company Regeneron is one of the few COVID specific treatments available to date, but it is expensive to produce and can only be treated with intravenous fluids. The development of antiviral drugs is incredibly challenging. The goal is to prevent the virus from replicating in an infected host. But that’s easier said than done. Because viruses hijack our natural cellular functions to replicate, an effective antiviral drug would need to disrupt some part of the virus’s life cycle without disrupting any of the mechanisms that are critical to our health.
One of the best-known antiviral drugs developed to treat influenza is called tamiflu. Its job is to block the action of proteins that the flu virus uses to move out of infected cells. The efficacy of tamiflu remains the source of much debate.
Redesivir is an antiviral drug that has received a lot of attention over the past year as a possible treatment for COVID-19. It was originally developed to treat hepatitis C, and after failing against that virus, it was repurloined to treat Ebola. It has a mild effect on Ebola.
Reddesivir was quickly reused last year to fight SARS-COV-2, but the results were decidedly mixed. Although the U.S. Food and Drug Administration has approved it to treat mild to severe hospitalized COVID-19 patients, the World Health Organization is taking a wait-and-see stance on its efficacy, stating that “there is currently no evidence that redesivir improves survival and other outcomes in these patients.”
Also, redesivir is not a pill. It requires intravenous fluids, limiting its use to patients who are already in hospitals.
There are dozens of antiviral TREATMENTS in development for COVID-19. Big drugmakers Merck and Pfizer are predictably the closest to the end, with a pair of oral antiviral COVID-19 treatments in advanced human clinical trials.
Merck’s drug candidate is called Monupilavir. It was first developed several years ago as an antiviral for influenza, however, preclinical studies have shown that it works well against both SARS and MERS coronaviruses.
Monupilavir is currently progressing into large phase 3 human trials. So far, the data are so promising that the U.S. government recently pre-ordered 1.7 million courses of the drug at a cost of $1.2 billion. If all goes according to plan, the company hopes the drug will be approved by the FDA for emergency use and be on the market by the end of 2021.
Pfizer’s large COVID-19 antiviral candidate is a bit more unique. Currently known as PF-07321332, the drug is the first oral antiviral specifically targeting SARS-CoV-2 to enter human clinical trials.
While this particular molecule was developed in 2020, after the emergence of the Novel Coronavirus, a somewhat related drug called PF-00835231 has been in the works for several years, targeting the original SARS virus. However, the new drug candidate, PF-07321332, is designed as a simple pill that can be administered in non-hospital conditions during the initial stages of SARS-CoV-2 infection.
“The protease inhibitor binds to a viral enzyme and prevents the virus from replicating in cells,” Pfizer said, explaining the mechanism of its new antiviral drug. Protease inhibitors have been effective in treating other viral pathogens, such as HIV and hepatitis C virus, either alone or in combination with other antiviral drugs. Currently marketed therapeutics targeting viral proteases are generally non-toxic, so such molecules have the potential to provide a well-tolerated treatment for COVID-19.”
Phase 1 trials of the new antiviral drug begin in early 2021. No official results have been released, but the company recently released details of a phase 2/3 trial scheduled to begin this month, suggesting early data are promising. By the end of the year, it should be clear whether Pfizer’s antiviral is working. And it’s not the only oral antiviral therapy specifically targeting SARS-CoV-2.
In addition, Shionogi, a Japanese drug company, is currently conducting phase 1 trials of a protease inhibitor similar to SARS-CoV-2. This is called S-217622 and is another oral antiviral drug that it is hoped will provide people with an easy-to-take pill in the early stages of COVID-19.
The COVID-19 pandemic is far from over. The Delta mutant strain has quickly become the most prominent SARS-COV-2 strain worldwide. Although our vaccine is still being maintained, it is clear that we need more tools to fight this novel coronavirus. Delta will certainly not be the last new variant of SARS-CoV-2 we encounter.
The media argued that an effective antiviral drug to reduce the severity of illness in infected people would be a “game changer” tool, in addition to a vaccine that could widely prevent hospitalizations and deaths. A short course of pills taken at home at the first sign of illness could be the way out of the pandemic.