As the spread of COVID-19 affects people around the world, scientists have been working overtime to develop potential treatments. Among them is a University of Arizona researcher who recently identified four compounds that can block the replication of the virus within a cell, providing a promising starting point for the development of drugs that can treat the disease.
Jun Wang, Ph.D., an assistant professor of pharmacology and toxicology at the UA, has spent much of his career studying respiratory viruses, including influenza A and B, and has directed his research toward developing antivirals that reduce the ability of a virus to spread.
Three months ago, Wang and his team began to reallocate their resources to help tackle SARS-CoV-2, the virus that causes COVID-19.
“With the COVID-19 pandemic, we feel that we have the obligation or the responsibility to help make a difference,” Wang said. “With whatever we do, we hope to make a practical impact and benefit the general population.”
There are many similarities between the COVID-19 virus and influenza, including the way they replicate within a person’s respiratory system, according to Wang.
The virus enters the body through the nose, mouth or eyes, where it then attaches to cells in the airway. The virus infects the cell by releasing a portion of its genetic material. The infected cell reads that genetic material and begins making proteins that will assemble new copies of the virus and essentially keep the immune system at bay.
To prevent the cell from creating new copies of the virus, Wang and his team needed to find compounds that could target the proteins and stop the virus in its tracks.
“If we can find a small molecule that can effectively stop the virus from replicating, and if we can provide such a drug early enough, it’s going to make a huge difference,” he said.
In order to make this happen, Wang targeted a protein within the virus called the main protease, which plays an essential role in the viral replication cycle. Inhibiting the activity of this protein blocks the replication cycle, which prevents the virus from infecting more cells, spreading to a new host and making more people sick.
“We designed experiments to identify small molecules that can inhibit the replication activity of the main protease. Luckily, we identified four of them that are most promising,” Wang said. “Basically what we did was let the virus infect the cells. Without any inhibitors, the virus is going to replicate in the cell and eventually cause cell death. When we treated the virus with these four compounds, we found that each of them could completely prevent the virus induced cell death.”
All four of the compounds demonstrated significant antiviral activity against SARS-CoV-2. Among them is an already FDA-approved compound called Boceprevir, which is used to treat Hepatitis C.
This compound has already been through Phase 1 clinical trials and its effective dosage is well-known, making it easier for clinicians to begin clinical trials to evaluate its benefit for COVID-19 patients.
Another one of the compounds, called GC-376, is an investigational veterinary drug being used to treat a strain of coronavirus in cats. According to Wang, the mortality rate for this particular strain of coronavirus in felines is 100%, which is why veterinary researchers have been testing the ability of this compound to stop the virus from spreading. Wang and his team say this compound can be repurposed for humans. More testing would need to be done with animals, however, before human trials can begin.
Once these drugs are evaluated and considered safe for human use, Wang said, they would have the ability to significantly reduce the mortality rate of COVID-19. The key, he said, is to provide the treatment to patients during the early incubation phase, when the symptoms are still mild and before the virus has had the chance to replicate too much and kill off the host’s healthy cells.
“At this point, if this is not under control, the viral infection will trigger a really intense immune response,” he said. “Most patients will have high fever, coughing, shortness of breath and all kinds of problems. So, to prevent the disease from progression from the mild to the intense phase, we need what we call an antiviral drug to suppress the replication.”
Wang and his team are now working to spread the word about these antiviral compounds and their success against the SARS-CoV-2 virus.
“We want to come up with an antiviral so that people don’t have to suffer from the COVID-19 disease. We cannot do this alone. We need support from the public,” he said. “The antiviral can help prevent infection and mitigate the disease. But we can’t expect a magic drug to save everybody’s life. If the disease has already progressed to the severe phase, the damage is already done. To really prevent the disease from spreading, we have to follow the CDC guidelines and trust the experts.”
Contact reporter Jasmine Demers at firstname.lastname@example.org
On Twitter: @JasmineADemers
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