Researchers have identified a compound that inhibits an enzyme crucial to the life cycle of coronaviruses, which cause the deadly Middle East respiratory syndrome and severe acute respiratory syndrome.
The discovery could put scientists closer to a treatment for MERS, which has spread to 20 different countries, causing 837 infections with 291 deaths since it was first detected in Saudi Arabia in 2012. Its cousin, SARS, sparked a fatal global outbreak in 2003, resulting in 800 deaths. There are no drugs available to treat either infection.
Investigators from the University of Illinois, Chicago, found that the compound, which inhibits an enzyme known as papain-like protease (PLpro), seems to work against MERS and SARS in slightly different ways due to variances in each virus' enzyme.
The research, presented this week at the Interscience Conference on Antimicrobial Agents and Chemotherapy in Washington, DC, suggests that finding other compounds that inhibit both may be difficult, according to the study authors.
Scientists have been studying PLpro in association with SARS coronavirus for years. The University of Illinois researchers tested four compounds--two from each group of the two known SARS PLpro inhibitors-for their ability to inhibit PLpro in MERS. Surprisingly, all four of the existing SARS PLpro inhibitors were ineffective against MERS.
After examining the structure of the PLpro enzymes in both viruses and finding a key difference, investigators searched a compound library and found an antimicrobial that could target both PLpro enzymes.
"Even when we solved the crystal structure of MERS-CoV PLpro, we observed that SARS and MERS PLpro share very similar overall structures including catalytic sites. However, after we closely examined the structural difference further, it was clear that there was a significant difference in blocking loop 2 that played a crucial role in SARS-CoV PLpro inhibitor binding," principle investigator Michael Johnson said in a statement.
- get the press release