Scientists have identified a novel target for a drug that can treat the SARS-CoV-2 virus, which causes COVID-19, and also help tackle a future coronavirus pandemic. The researchers at Northwestern University Feinberg School of Medicine in the US noted that scientists should prepare for a possible next coronavirus pandemic.
"God forbid we need this, but we will be ready," said Karla Satchell, professor of microbiology-immunology at Feinberg School of Medicine. The team previously mapped the structure of a virus protein called nsp16, which is present in all coronaviruses.
The latest study, published in the journal Science Signaling, provides critical information that could aid drug development against future coronaviruses as well as SARS-CoV-2. "There is great need for new approaches to drug discovery to combat the SARS-CoV-2/COVID-19 pandemic and infections from future coronaviruses," Satchell said.
The idea behind the future drug would be that it works early in the infection. "If somebody around you gets the coronavirus, you would run to the drugstore to get your medication and take it for three or four days. If you were sick, you wouldn't get as sick," Satchell explained.
The researchers mapped three new protein structures in three-dimensional views and discovered a secret identifier in the machinery that helps the virus hide from the immune system. They found a coronavirus-specific pocket in the protein, nsp16, that binds the virus-genomic fragment held in place by a metal ion.
The fragment is used by the coronavirus as the template for all the viral building blocks. There is potential to make a drug to fit this unique pocket that would block function of this protein from the coronavirus, the researchers said.
It would not block the function of a similar protein from human cells that lacks the pocket, they said, adding such a drug would only target the invader protein. Nsp16 is considered one of the key viral proteins that could be inhibited by drugs to stop the virus shortly after a person gets exposed.
The goal, researchers said, is to stop the virus early before people get too sick. The team worked to generate key information about this protein and is collaborating with chemists who will use the information to design drugs against the protein.
The researchers noted that while some of the coronavirus proteins vary a lot, nsp16 is nearly the same across most of them. The unique pocket discovered by the team is present in all the different coronavirus members.
This means that drugs designed to fit this pocket should work against all coronaviruses, including a virus that emerges in the future, according to the researchers. It should also work against the common cold that is caused by a coronavirus, they said.
The researchers envision any drug developed based on the team's finding of the coronavirus pocket would be part of a treatment cocktail taken by patients early in the course of the disease. That could include drugs similar to Remdesivir, that prevents the virus from producing the template for the building blocks that is necessary for it to replicate itself, they added.
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