A new analysis reveals that several drugs already approved for use in other diseases may also work as treatments for COVID-19. Photo by Steve Buissinne from Pixabay
Drugs cleared for treating diseases such as Type 2 diabetes, hepatitis C and HIV may stop the Delta variant of COVID-19 from replicating in, or infecting and spreading in, human cells, an analysis published Friday by Communications Biology found.
After testing 64 drugs approved by the Food and Drug Administration for use in other diseases, the researchers identified eight that block activity of certain viral enzymes, called proteases, that are essential for replication of the virus that causes COVID-19 to replicate in infected human cells.
The identified drugs include the blood sugar-control medication sitagliptin, sold under the brand name Januvia, among others, and the hepatitis C treatments daclatasvir, sold under the brand name Daklinza, and lycorine HCl, the researchers said.
Other drugs showing potential were the HIV medications MG-101 and nelfinavir mesylate, they said.
“Our research shows that repurposing certain FDA-approved drugs … may be a useful strategy in the fight against [COVID-19],” study co-author Joyce Jose said in a press release.
“The development of broad-spectrum antiviral drugs against a wide range of coronaviruses is the ultimate treatment strategy for circulating and emerging coronavirus infections,” said Jose, an assistant professor of biochemistry and molecular biology at Penn State University.
Earlier studies have shown that two enzymes, the proteases Mpro and PLpro, play a key role in the spread of the virus that causes COVID-19 in human cells.
This makes them potential targets for treatments for the disease, particularly since they are relatively stable, meaning they are unlikely to develop drug-resistant mutations quickly, Jose and her colleagues said.
For example, the COVID-19 drug paxlovid, developed by Pfizer, targets Mpro, according to the researchers.
The virus that causes the disease “produces long proteins, called polyproteins, from its RNA genome that must be cleaved into individual proteins” by Mpro and PLpro,” co-author Katsuhiko Murakami said in a press release.
Therefore, “if you inhibit one of these proteases, further spread of [the virus] in the infected person could be stopped,” said Murakami, a professor of biochemistry and molecular biology at Penn State.
Researchers developed their own procedure for testing drugs and then used it to assess 64 medications for their ability to block production and activity of Mpro or PLpro.
From the 64 compounds, they identified eleven that affected Mpro activity and five that affected PLpro activity, they said.
In subsequent experiments, the team evaluated the antiviral activity of the 16 drugs against the virus that causes COVID-19, specifically the Delta variant.
Sitagliptin and paclatasvir inhibit PLpro, while MG-101, lycorine HCl and nelfinavir mesylate inhibit Mpro, the researchers said.
Of these, MG-101 also hindered the virus’ ability to infect cells by inhibiting protease processing of its spike protein, they said.
In addition, treating cells with a combination of Mpro and PLpro inhibitors produced a stronger antiviral effect, providing even greater inhibition of virus replication, according to the researchers.
Although they studied the Delta variant of the virus, the drugs will likely be effective against Omicron and future variants because they target parts of the virus that are unlikely to mutate significantly, the researchers said.
They are in the process of developing new drugs that inhibit both Mpro and PLpro to treat COVID-19, they said.
“In cell culture, we showed that if you combine Mpro and PLpro inhibitors, you have a stronger effect on the virus without increasing toxicity,” Jose said.
“This combination inhibition is highly potent,” she said.