If last year was all about repurposing old drugs to target COVID-19 while developing vaccines, the focus of much research this year is certainly on producing novel antiviral drugs to help treat those sick with the disease. While many have reasonably focused on vaccines to help prevent hospitalizations and deaths, they are only one part of the armory necessary in battling this novel coronavirus.
Not everyone can, or will, get vaccinated. For some people, such as the immunocompromised, vaccines are not particularly effective. And despite our best efforts, vaccines will never be 100 percent effective at stopping transmission or infection.
For now our COVID-19 vaccines are powerful tools helping save lives. They inarguably break the link between infection, hospitalization and death, turning a severe, deadly disease into something more manageable, albeit still not pleasant.
The $3-billion-dollar plan
In June the US government launched a new program called the Antiviral Program for Pandemics (APP), which will see over US$3 billion dollars invested in developing antiviral drugs to treat COVID-19.
As Anthony Fauci, director of the 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 develop.
“I wake up in the morning, I don’t feel very well, my sense of smell and taste go away, I get a sore throat,” Fauci explained to The New York Times. “I call up my doctor and I say, ‘I have COVID and I need a prescription.’”
Antivirals aren't easy to design
Current treatments for patients sick with COVID-19 are relatively limited. A novel antibody treatment produced by pharma company Regeneron is one of the few COVID-specific treatments to appear so far, but it is expensive to produce and can only be administered by intravenous infusion.
Antiviral drugs are incredibly challenging to develop. The goal is to stop a virus replicating inside an infected host. But that is easier said than done.
Because viruses hijack our natural cellular functions to replicate, an effective antiviral drug needs to disrupt some part of a virus's lifecycle without messing up any mechanism vital to our health.
One of the most well known antiviral drugs developed to treat influenza is known as Tamiflu. It works by blocking the action of a protein the flu virus uses to move out of an infected cell. The efficacy of Tamiflu is still the source of much debate.
Remdesivir is an antiviral drug that received lots of attention over the past year as a possible treatment for COVID-19. It was originally developed to treat hepatitis C, and after failing to work against that virus it was repurposed to treat Ebola. It was mildly effective against Ebola.
Remdesivir was quickly repurposed to fight SARS-CoV-2 last year, but the results have been decidedly mixed. Although the US Food and Drug Administration has approved it to treat mild to severe hospitalized COVID-19 patients, the World Health Organization is still on the fence about its efficacy, claiming, “there is currently no evidence that remdesivir improves survival and other outcomes in these patients.”
Plus, remdesivir is not a pill. It requires intravenous infusion, limiting its uses to those already sick in hospital.
So what is on the horizon?
Several dozen antiviral COVID-19 treatments are currently in development. Big pharma power players Merck and Pfizer unsurprisingly are closest to the finish line with a pair of oral antiviral COVID-19 treatments in advanced human clinical trials.
Merck’s candidate is called molnupiravir. It was originally developed several years ago as an influenza antiviral, however, preclinical studies demonstrated promising efficacy against both SARS and MERS coronaviruses.
Molnupiravir is currently deep in large Phase 3 human trials. So far the data is so promising the US government recently put in a pre-order for 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 authorized for emergency use by the FDA and is available before the end of 2021.
Pfizer’s big COVID-19 antiviral candidate is a little more unique. Currently dubbed PF-07321332, the drug is the first oral antiviral drug to reach human clinical trials that is specifically designed to target SARS-CoV-2.
While this particular molecule was developed in 2020 after the novel coronavirus appeared, a somewhat related drug called PF-00835231 has been in the works for several years, targeting the original SARS virus. The new candidate, PF-07321332, however, has been designed to be a simple pill that can be taken in non-hospital conditions at the very beginning of a SARS-CoV-2 infection.
“Protease inhibitors bind to a viral enzyme (called a protease), preventing the virus from replicating in the cell,” says Pfizer, explaining the mechanism behind its novel antiviral drug. “Protease inhibitors have been effective at treating other viral pathogens such as HIV and hepatitis C virus, both alone and in combination with other antivirals. Currently marketed therapeutics that target viral proteases are not generally associated with toxicity and as such, this class of molecules may potentially provide well-tolerated treatments against COVID-19.”
Phase 1 trials for the novel antiviral began early in 2021. No results have been officially announced but the company has recently posted details for a Phase 2/3 trial set to commence this month, suggesting promising early data.
By the end of the year it should be clear whether Pfizer's antiviral drug is working. And it isn’t the only oral antiviral treatment specifically designed to target SARS-CoV-2.
A Japanese company called Shionogi is currently in Phase 1 trials testing a similar protease inhibitor for SARS-CoV-2. Called S-217622, this is another oral antiviral that is hoped to offer people an easy pill to take in the early stages of COVID-19.
The COVID-19 pandemic is far from over. The Delta variant has swiftly become the most prominent strain of SARS-CoV-2 around the world. Although our vaccines are still holding up it is clear we need more tools to fight this novel coronavirus. Delta will surely not be the last new SARS-CoV-2 variant we encounter.
Alongside vaccines that broadly prevent hospitalization and death, an effective antiviral to reduce the severity of disease in those infected would be a game-changer. A short course of pills taken at home at the first sign of disease may be the way out of this pandemic.
