South China Morning Post

Study finds virus can form resistance to key treatment

- Holly Chik holly.chik@scmp.com

The Covid-19 virus can develop partial resistance to the antiviral medication remdesivir, a laboratory study has shown.

Researcher­s in the United States and Canada found that Sars-CoV-2, the official name of the coronaviru­s, developed mutations that enabled it to partially evade remdesivir’s antiviral effect upon repeated exposure to the parent molecule used to make the drug in cell culture.

The researcher­s said that despite very few reports of patient resistance to remdesivir, it was vital to understand­ing factors that promoted or prevented resistance to the drug so that it could continue to be used to treat Covid19 and other coronaviru­ses.

Remdesivir is a treatment given by injection that stops the coronaviru­s by preventing its RNA genome from being copied.

The World Health Organizati­on updated its guidelines in April to suggest remdesivir for treating mild or moderate Covid-19 patients at high risk of hospitalis­ation, reversing a 2020 recommenda­tion against its use.

The update is based on phase 3 trial data that showed a threeday course of the drug vastly reduced the risk of hospitalis­ation for patients at high risk of disease progressio­n, according to its developer Gilead Sciences.

In 2020 the drug was approved by the US Food and Drug Administra­tion as the first Covid19 treatment for people aged over 12. In April, the FDA also approved its use in high-risk children older than 28 days.

Meanwhile in Hong Kong, the drug has been approved for use among patients with moderate symptoms or those that require oxygen therapy.

In the new study, researcher­s found the coronaviru­s developed mutations in the polymerase – a type of enzyme that copies the RNA genome – which emerged after prolonged exposure of the virus to the drug.

“Our studies present potential pathways to resistance for SarsCoV-2 to remdesivir and provide multiple mechanisms of resistance that the virus uses to overcome sensitivit­y to remdesivir,” the team from North America wrote in the journal Science

Translatio­nal Medicine last week. “Our results create a reference for surveillan­ce for remdesivir resistance, and support the need to pursue combinatio­n therapies targeting the RdRp [the polymerase enzyme that replicates the genome of the virus] through different mechanisms.”

Mark Denison, the lead author and head of a US coronaviru­s lab at Vanderbilt University Medical Centre that led the developmen­t of remdesivir, said the drug remained a key treatment that limited illnesses, hospitalis­ations and deaths from the virus.

“To date, there have been very few reports of resistance to remdesivir in clinical practice. We must be sure that we can continue to use this antiviral against Covid19, future human coronaviru­ses and potentiall­y even against our known human coronaviru­ses.

“So, it is critical to understand how coronaviru­ses might try to escape from the drug, and to use that data to monitor for any potential emergence of resistance in Covid-19 patients,” he said.

We must be sure that we can continue to use this antiviral against Covid-19

MARK DENISON, LEAD AUTHOR

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