Coronavirus Variant Hunters Stay Ready

When a new coronavirus variant emerges, Gilead Sciences virologists Charlotte Hedskog and John Bilello, alongside their teams, mobilize as so-called "variant hunters."

They aim to determine whether COVID-19 therapeutics will remain active against new strains.

The process demands perseverance and collaboration, as the results broadly affect treating people worldwide with COVID-19.

"It can be a challenging process for sure as some variants are harder to find," said Charlotte, Senior Research Scientist on the Clinical Virology team, in a January 12, 2023 press release.

But the teams of experts are up to the task.

Since the SARS-CoV-2 2 virus emerged and spread globally in late 2019 and early 2020, scientists have tested more than 15 genetic variants which cause COVID-19.

"This is a process that involves many people with a commitment to collaboration - internally and externally," says John, Director of Virology, who leads the COVID-19 Discovery Virology team.

"We all rely on each other to find these isolates and identify which ones to go after."

The work begins when the U.S.Centers for Disease Control and Prevention (CDC) or the World Health Organization (WHO) issues an alert signaling a new SARS-CoV-2 "variant of concern" (VoC). 

When a genetically different virus strain is rising in transmission rate, causing more severe disease, or possibly capable of evading vaccines, therapeutic antibodies, or antivirals.

"When we hear that there is something new, we immediately reach out to our collaborators," says Charlotte.

John, Charlotte, and their colleagues have developed many connections with domestic and international academic collaborators who have isolated new variants they were looking for.

For example, early in the pandemic, the scientists worked with collaborators to obtain the isolated strain from the first reported case of COVID-19 in the United States, identified in Washington State.

"Recently, the team has established a partner in India and is also reaching out to other potential partners worldwide," says Charlotte.

"This includes South Africa, where the Omicron virus was first identified."

The evolving virus reappears in different forms worldwide, and sometimes it can be hard to pin down an isolated sample of a new variant.

So when the variant is found, Gilead applies to the CDC for a special permit to ship it to its labs in Foster City.

Once in hand, trained laboratory personnel in both the Clinical and Discovery Virology teams examine it in a specialized biosafety lab built in 2020 to study SARS-CoV-2. Next, they test how the virus samples respond when exposed to different levels of COVID-19 therapeutics.

If the level of therapeutics needed to inhibit the virus doesn't change, the drug maintains its full activity against the new variant in a laboratory environment.

The team used this method to test all the major prior variants and the recent Omicron BA.4 and BA.5 subvariants.

To streamline the testing process, the researchers are now developing a method to create an engineered version of a variant in the lab based on the available genetic sequencing data.

These 'replicons' are a valuable alternative for testing COVID-19 therapeutics against new strains.

"The 'replicons' would support producing results much faster, which is important to ultimately help people with a new COVID-19 variant faster," says Charlotte.

"As the COVID-19 pandemic continues to evolve, new variants of concern will certainly emerge. Therefore, we must continue monitoring these variants and generating antiviral data for potential future VoC."

Note: The full, unedited Jam. 12, 2023, press release is posted at this link.