Skip to main content
Move the World.
main protease

Lead Image Courtesy of Oak Ridge National Laboratory

At this point, we are all familiar with SARS-CoV-2, the virus that causes COVID-19, and its infamous spike protein, which it uses to crack open our cells and crank out copies of itself like a horrifying Xerox machine. 

The spike has been a big target of scientific interest: two vaccines, by Pfizer and Moderna, are based on it and have recently reported efficacies of over 90%. 

But for treating COVID-19, there are other proteins inside our tiny foe that may be better targets. 

One is an enzyme called the main protease.

When SARS-CoV-2 is hijacking your cells to replicate itself, it creates long chains, called polyproteins. But in order for them to do anything, these chains need chopped up into individual workable proteins — that's the main protease's job. 

Stop the main protease from slicing the proteins, stop the virus's replication.

Now, researchers at the Oak Ridge National Laboratory (ORNL) believe that hepatitis C drugs may be able to do just that.

Looking to the Cures We Already Have

Their study, published in Structure, used room temperature x-rays to create a detailed, 3D model of the main protease, showing the exact arrangement of its atoms and where the hep C drug's chemical bonds would occur.

"What we found is that hepatitis C drugs bind to and inhibit the coronavirus protease," lead author Daniel Kneller said in a press release. "This is an important first step in determining whether these drugs should be considered as potential repurposing candidates to treat COVID-19."

The team studied three protease inhibitors already approved by the FDA for treating hepatitis C — boceprevir, narlaprevir, and telaprevir. 

Debuting in 2011, a combination of these drugs can now cure about 95% of hepatitis C infections — an amazing achievement for a deadly disease that was only discovered in 1989. 

Hepatitis C is the first (and so far only) chronic viral disease to be cured — and protease inhibitors were the key.

To see how effective these drugs were at binding to the main protease, they used a process called "in vitro enzyme kinetics" to study how well the drugs bind to SARS-CoV-2 in a test tube. Drugs with a high "binding affinity" stick better to the main protease.

They found that the hepatitis C drugs (especially boceprevir and narlaprevir) had a high binding affinity — and therefore, the potential to gum up that main protease.

Repurposing Drugs

Drugs we already know well and have already been studied and approved by the FDA are our best shot of rapidly finding a good COVID-19 treatment. 

"What we're doing is laying the molecular foundation for these potential drug repurposing inhibitors by revealing their mode of action," said ORNL's Andrey Kovalevsky. 

"We show on a molecular level how they bind, where they bind, and what they're doing to the enzyme shape. And, with in vitro kinetics, we also know how well they bind. Each piece of information gets us one step closer to realizing how to stop the virus."

Stop SARS-CoV-2's main protease from slicing the proteins, stop the virus's replication.

They also found out something unusual about the main protease in the process: it can change its shape, altering itself with the size and structure of the inhibitor drugs glommed on to it. 

As per usual, the COVID caveats apply. This is early work; it has identified potential drug candidates, not a proven cure. 

Another wrinkle: hep C drugs are wildly expensive, which may make them less-than-ideal options in a practical sense.

Up Next

If you want to understand a problem, talk to the people working on solutions. Join us as we meet the people and explore the ideas on the frontlines of an unprecedented global response.

Computer Science
Crowdsourcing the Seed for Coronavirus Antiviral Medications
antiviral medications
Computer Science
Crowdsourcing the Seed for Coronavirus Antiviral Medications
Foldit players are solving a protein structure puzzle that could help kickstart coronavirus antiviral medications.

Foldit players are solving a protein structure puzzle that could help kickstart coronavirus antiviral medications.

Coronavirus
Coronavirus Nasal Spray Vaccine Nears Human Trials
Coronavirus Nasal Spray Vaccine
Coronavirus
Coronavirus Nasal Spray Vaccine Nears Human Trials
A nasal spray vaccine for COVID-19 that contains a live coronavirus genetically engineered to replicate more slowly is nearing human trials.

A nasal spray vaccine for COVID-19 that contains a live coronavirus genetically engineered to replicate more slowly is nearing human trials.

Coronavirus
Researchers Found Tiny COVID-19 Antibodies In An Alpaca
nanobodies
Coronavirus
Researchers Found Tiny COVID-19 Antibodies In An Alpaca
Inside an alpaca’s blood, researchers have found tiny antibodies — nanobodies — that may lead to future antiviral medications.

Inside an alpaca’s blood, researchers have found tiny antibodies — nanobodies — that may lead to future antiviral medications.

Coronavirus
The Social Distancing Traffic Light
social distancing
Coronavirus
The Social Distancing Traffic Light
Assessing your COVID-19 risk for everyday activities will be key to some kind of normalcy. Now, researchers want to add nuance to social distancing.

Assessing your COVID-19 risk for everyday activities will be key to some kind of normalcy. Now, researchers want to add nuance to social distancing.

Coronavirus
Can The Common Cold Help Battle COVID-19?
Can The Common Cold Help Battle COVID-19?
Coronavirus
Can The Common Cold Help Battle COVID-19?
The common cold can be caused by a coronavirus. New research suggests the immune response it causes may help protect against COVID-19.

The common cold can be caused by a coronavirus. New research suggests the immune response it causes may help protect against COVID-19.

Coronavirus
Gates Foundation Backs a $3 Coronavirus Vaccine
$3 Coronavirus Vaccine
Coronavirus
Gates Foundation Backs a $3 Coronavirus Vaccine
The Gates Foundation is spending $150 million to help with the manufacturing and distribution of a $3 coronavirus vaccine in lower-income nations.

The Gates Foundation is spending $150 million to help with the manufacturing and distribution of a $3 coronavirus vaccine in lower-income nations.

Coronavirus
New Air Filter for COVID-19 Could Lower Risk of Being Indoors
Air Filter for COVID-19
Coronavirus
New Air Filter for COVID-19 Could Lower Risk of Being Indoors
A new air filter for COVID-19 heats up to nearly 400 degrees Fahrenheit to kill the coronavirus in aerosols.

A new air filter for COVID-19 heats up to nearly 400 degrees Fahrenheit to kill the coronavirus in aerosols.

Coronavirus
Pfizer’s COVID-19 Vaccine Produces More Antibodies Than the Disease Itself
Pfizer’s COVID-19 Vaccine
Coronavirus
Pfizer’s COVID-19 Vaccine Produces More Antibodies Than the Disease Itself
Early data shows Pfizer’s COVID-19 vaccine produces immunity as good as, or better than, recovery from the virus.

Early data shows Pfizer’s COVID-19 vaccine produces immunity as good as, or better than, recovery from the virus.

Public Health
Doctors Test Solution for COVID-19 Phenomena, Silent Hypoxia
Silent Hypoxia
Public Health
Doctors Test Solution for COVID-19 Phenomena, Silent Hypoxia
Doctors treating COVID-19 patients are testing the ability of common blood thinners to address silent hypoxia, one of the disease’s most alarming phenomena.

Doctors treating COVID-19 patients are testing the ability of common blood thinners to address silent hypoxia, one of the disease’s most alarming phenomena.