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How, exactly, does the coronavirus hijack and reprogram human cells to sicken and kill?
This question has obsessed Nevan Krogan since February, when the UCSF virus expert and his colleagues realized, before many did, that things in America would get very bad very fast.
Since then, the question has only grown more urgent, and for the past four months, Krogan and an ever-expanding team of scientific collaborators in San Francisco and around the world have turned their labs upside down, prying out secrets of the virus that might point to a cure.
They have built an innovative system for quickly generating clues about the virus’ weak spots and using those clues to search vast drug databases for existing drugs that might stop it in its tracks. First, they assembled a first-of-its-kind map of the virus’ inner workings, exploiting the map to pinpoint 10 old drugs and compounds that kill the virus in lab tests and could ultimately become drugs for treating COVID-19.
Now the UCSF-led group has used similar techniques to explore the biology of the virus at a deeper level, flagging a new class of drug candidates that function through a different, powerful mechanism.
And this time, the scientists have taken photos of the virus as it infects host cells, providing some of the first sharp visual images of the deadly pathogen at work — and exposing weird cellular structures created by the virus that have never been seen before and that may help explain why it is so infectious.
“The more you understand this creature, the better you can fight it,” said Krogan, a molecular biologist at UCSF and an investigator with the Gladstone Institutes who led the large research team. “So we’re trying to understand as much as possible about how the virus infects us.”
Krogan directs the Quantitative Biosciences Institute within UCSF’s School of Pharmacy, a coalition of 100 research laboratories that often work together on projects, generating reams of biological data and sifting those data sets for clues about fighting disease.
The new findings, expected to be published Saturday in the prestigious journal Cell, emerged from a joint effort of 22 QBI labs that are aiming their energies at the virus. Dubbed the…