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Scientists have identified several existing compounds that block the replication of the COVID-19-causing SARS-CoV-2 virus within human cells grown in the laboratory, by targeting a key viral enzyme.
The inhibitors all demonstrated potent chemical and structural interactions with viral proteins critical to the virus's ability to proliferate, according to the study published in the journal Cell Research.
The most promising drug candidates -- including the USFDA-approved hepatitis C medication boceprevir and an investigational veterinary antiviral drug known as GC-376 -- target the SARS-CoV-2 main protease (Mpro) enzyme, the researchers from the University of South Florida (USF) in the US said.
The enzyme cuts out proteins from a long strand that the virus produces when it invades a human cell, they said.
The researchers noted that without Mpro, the virus cannot replicate and infect new cells.
This enzyme had already been validated as an antiviral drug target for the SARS and MERS, both genetically similar to SARS-CoV-2, they said.
"With a rapidly emerging infectious disease like COVID-19, we don't have time to develop new antiviral drugs from scratch," said Yu Chen, an associate professor at USF.
"A lot of good drug candidates are already out there as a starting point. But, with new information from studies like ours and current technology, we can help design even better drugs much faster," said Chen.
Mpro represents an attractive target for drug development against COVID-19 because of the enzyme's essential role in the life cycle of the coronavirus and the absence of a similar protease in humans, Chen noted.
Since people do not have the enzyme, drugs targeting this protein are less likely to cause side effects, he explained.
The team, including researchers from the University of Arizona in the US, identified four leading drug candidates as the most potent and specific for fighting COVID-19.
These are Boceprevir, a drug to treat Hepatitis C, GC-376 -- an investigational veterinary drug for a deadly strain of coronavirus in cats -- and Calpain inhibitors II and XII, investigated in the past for cancer, neurodegenerative diseases and other conditions, they said.
All four compounds were superior to other Mpro inhibitors previously identified as suitable to clinically evaluate for treating SARS-CoV-2, Chen added.
