Michael Waldholz in Scientific American:
Mark Denison began hunting for a drug to treat COVID-19 almost a decade before the contagion, driven by a novel coronavirus, devastated the world this year. Denison is not a prophet, but he is a virologist and an expert on the often deadly coronavirus family, members of which also caused the SARS outbreak in 2002 and the MERS eruption in 2012. It is a big viral group, and “we were pretty certain another one would soon emerge,” says Denison, who directs the division of pediatric infectious diseases at Vanderbilt University Medical Center.
A virus is an unusual beast. Essentially it is a cluster of genetic material that integrates itself into a cell and takes over some of the cell’s molecular machinery, using it to assemble an army of viral copies. Those clones burst out of the cell, destroying it, and go on to infect nearby cells. Viruses are hard to kill off completely because of their cellular integration—they hide within their hosts. And they have explosive reproductive rates. Because total eradication is so hard, antiviral drugs instead aim to limit replication to low levels that cannot hurt the body.
In 2013 Denison and Ralph Baric, a coronavirus researcher at the University of North Carolina at Chapel Hill, identified a vulnerable site on a protein common to all coronaviruses they had examined, a spot that is key to the microbe’s ability to make copies of itself. If that ability is hindered, a coronavirus cannot cause widespread infection. Four years later researchers in the two laboratories spotted a compound that acted on this protein site. It was sitting, unused, in a large library of antiviral compounds created by the biotech giant Gilead Biosciences. The scientists got a sample and, in test tube and animal experiments, showed that the drug, called remdesivir, shut down the replicating machinery of several coronavirus variants.