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BloombergBusinessweek May 18, 2020inthisgroup,MarkDenisonofVanderbiltUniversityMedical
CenterandRalphBaricoftheUniversityofNorthCarolinaat
ChapelHill,hadworkedtogetheroncoronaviruses for years.
Baric first warned about the potential for them to cause signif-
icant human disease back in the late 1990s.
DenisonwasskepticaltheGileadcompoundswoulddo
much.Butwhenhetestedananalogofremdesiviragainsta
mousecoronavirus in his lab, it worked. Over the next few
years, Baric and his UNC colleague Timothy Sheahan tested
the drug against SARS virus, MERS virus, and numerous other
bat coronaviruses. Remdesivir worked better than almost any
other drug they tried. “Every virus we tested it on, it had very
high potency and efficacy,” Denison recalls.
In 2018 another Ebola outbreak flared up in the Congo, giv-
ing Gilead an opportunity to finally test remdesivir in people
with Ebola. It didn’t work. But the trials proved one thing: The
drug was safe. Gilead was figuring out what to do with the com-
pound next, says Cihlar, when Covid-19 came along.KEN KENT, GILEAD’S VICE PRESIDENT IN CHARGE OF
chemical development and manufacturing, compares drug
manufacturing to baking giant quantities of a very compli-
cated bread: You have to perform all the right steps in pre-
cisely the right sequence. And just as a baker needs a particular
flour to make a signature bread, a pharmaceutical chemist
must have sufficient quantities of all the right ingredients on
hand. “If you have to wait for the wheat to grow,” Kent says,
“it’s going to take a while.”
Kent joined Gilead in the late 1980s—he was employee No.8—
andhasbeeninvolvedinonewayoranotherwithmanyofits
antiviralhits,includingTamiflu,Sovaldi,andTruvada,a big-
sellingprophylacticHIVdrugcombination.Todayhe’sincharge
ofproducingtheactiveingredientsforallofGilead’s“small-
molecule”drugs.That’sindustryjargonforpillsandother
medicinesmadethroughtraditionalchemistry,asopposedto
DNA-orprotein-based concoctions, which are produced using
genetic engineering and brewed inside living cells. While rem-
desivir isn’t a pill, it is a smaller molecule.
In mid-January, Kent got a call from Reza Oliyai, senior vice
president for Gilead’s pharmaceutical operations, telling him
the company would need to make large quantities of remde-
sivir to fight the novel coronavirus. Kent immediately started
calculating how long that would take. “We had to move quick,
because the one thing you can’t buy is time,” he says. “When
you have long linear chemical synthesis, that has to be done
sequentially A to B to C, that’s time you just can’t get back.”
Depending on how you count, there are about 25 chemi-
cal steps in the production process. Most drugs require about
half that number. Some of the steps are more delicate than oth-
ers. An early one uses a reagent so flammable it will sponta-
neously combust if exposed to air. Another involves a poison
called trimethylsilyl cyanide. “If you get it on your body you
better get yourself to the hospital really quick,” says Howard
University chemist Joseph Fortunak, who’s analyzed the remde-
sivir manufacturing process. “And you still might not survive.”↑Gilead says it will give
away the first 1.5 million
vials it produces↓Vials are loaded into the
filling machine