New Understanding of How Gilead’s Remdesivir Inhibits SARS-CoV-2 Could Help Develop COVID-19 Antivirals

A study has shed new light on Gilead Sciences’ (Foster City, CA, USA) COVID-19 antiviral drug remdesivir, paving the way for more effective antiviral treatments.

For the first time, scientists at The University of Texas at Austin (Austin, TX, USA) have identified a critical mechanism that the drug uses and unearthed information that drug companies can use to develop new and improved antivirals to take advantage of the same trick. The finding could also lead to more potent drugs, meaning a patient could take less of a dose, see fewer side effects and experience faster relief.

The team re-created in a lab dish the process that plays out in a patient who is infected with SARS-CoV-2 and then receives remdesivir. In a scientific first, the scientists developed a method for producing fully functional RNA polymerases to copy the viral genetic material. Next, they added a form of remdesivir. As the drug did its work, the researchers paused the process just after the reaction with remdesivir was completed (15-20 seconds) and took a 3D snapshot of the molecules in exquisite detail using a cryo-electron microscope. The image allowed them to reconstruct exactly how remdesivir gums up the copying process. The scientists liken the trick identified by them to a paper jam in the virus’s photocopier. Remdesivir shuts down this photocopier - called an RNA polymerase - by preventing copying of the virus’s genetic code and its ability to churn out duplicates and spread through the body. The team detected where the drug manages to gum up the gears, grinding the machine to a halt.

“Right now, it’s a five-day regimen of taking quite a bit of remdesivir,” said co-author Kenneth Johnson, professor of molecular biosciences at UT Austin. “That’s inconvenient and comes with side effects. What if you could take just one pill and that was all you needed to do? That would make a huge difference in terms of the here and now.”

“We might need other drugs that are like remdesivir, but different enough that they can then go after the mutated forms,” added Johnson. “It’s like having a backup system, like having an emergency parachute in case the main chute doesn’t work.”


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Gilead Sciences
The University of Texas at Austin