In a fight against Covid-19 pandemic, the researchers have found several existing compounds that block replication of the coronavirus (SARS-CoV-2) within human cells grown in the laboratory.
According to the study, published in the journal Cell Research, the inhibitors all demonstrated potent chemical and structural interactions with a viral protein critical to the virus's ability to proliferate.
"With a rapidly emerging infectious disease like Covid-19, we don't have time to develop new antiviral drugs from scratch," said study researcher Yu Chen from the University of South Florida in the US.
"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 (repurposed) drugs much faster," Chen added.
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).
Mpro is an enzyme that cuts out proteins from a long strand that the virus produces when it invades a human cell.
Without Mpro, the virus cannot replicate and infect new cells.
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.
Since people do not have the enzyme, drugs targeting this protein are less likely to cause side effects, they explained.
The research team identified four leading drug candidates as the most potent and specific for fighting Covid-19. These inhibitors rose to the top after screening more than 50 existing protease compounds for potential repurposing.
These are Boceprevir, a drug to treat Hepatitis C, GC-376, an investigational veterinary drug for a deadly strain of coronavirus in cats, which causes feline infectious peritonitis and Calpain inhibitors II and XII, investigated in the past for cancer, neurodegenerative diseases and other conditions, also showed strong antiviral activity.
"All four compounds were superior to other Mpro inhibitors previously identified as suitable to clinically evaluate for treating SARS-CoV-2," the study author noted.