Researchers have identified a compound that potently inhibits the replication of human coronaviruses, including those causing SARS and MERS, and could lead to antiviral drugs to stop them in their tracks.
Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is an infectious and potentially deadly form of pneumonia that emerged in the Guangdong province of southern China in 2002 and caused more than 8,000 infections and 774 deaths before being brought under control.
The related Middle East respiratory syndrome coronavirus (MERS-CoV) which emerged in Saudi Arabia in 2012, is less transmissible, but more virulent. There have been 636 confirmed cases of the virus, including 193 fatalities.
In the new study, led by Volker Thiel of the University of Bern in Switzerland, scientists screened more than 16,500 compounds for antiviral activity by adding them to cell cultures derived from human lung tissue. They identified a small molecule called K22 which effectively inhibited all the coronaviruses tested1.
A further series of experiments revealed its mode of action. In order to replicate, coronaviruses usurp and reorganize the membrane of its host cell to form vesicles, within which new viral particles are assembled. K22 blocks this early and crucial step of the coronavirus life cycle.
“The most exciting aspect of the discovery is that K22 targets a step in the viral life cycle that was not known to be druggable,” says Thiel. “People have to get vaccinated before the infection, [but] a small compound would have the advantage [to treat] infected people.”
Thiel pointed out that developing the drug for clinical application was a long and expensive path. “It would involve optimization of K22 based on its structure to obtain a tolerable and effective drug, in vivo assessment in animal models, and clinical trials in humans.”
In April, the Saudi Arabian government announced it had entered talks with pharmaceutical companies about manufacturing a MERS-CoV vaccine, and earlier this month two teams of researchers independently reported the identification of antibodies that can neutralize the virus.