When a new COVID-19 virus variant is discovered, Gilead virologists Charlotte Hedskog and John Bilello, along with their teams, mobilize as "variant hunters."
Their mission is to see if COVID-19 therapeutics will still be effective against new strains. The process necessitates perseverance and collaboration, as the results have far-reaching implications for treating people with COVID-19 all over the world.
“It can be a challenging process for sure as some variants are harder to find,” says Charlotte, Senior Research Scientist on the Clinical Virology team.
However, expert teams are up to the task. Since COVID-19 emerged and spread around the world in late 2019 and early 2020, scientists have tested more than 15 different genetic variants of SARS-CoV-2, the virus that causes 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 Centers for Disease Control and Prevention (CDC) or the World Health Organization (WHO) issues an alert indicating the presence of a new SARS-CoV-2 "variant of concern" - a genetically distinct virus strain that is increasing in transmission rate, causing more severe disease, or may be 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.
Over time, John, Charlotte, and their colleagues have made numerous connections with domestic and international academic collaborators who have isolated new variants they were looking for. Early in the pandemic, for example, the scientists collaborated with collaborators to obtain the isolated strain from the first reported case of COVID-19 in the United States, which was identified in Washington State.
“Recently, the team has established a partner in India and is also reaching out to other potential partners around the world,” says Charlotte. “This includes South Africa, where the Omicron virus was first identified.”
Testing a New Variant
The virus continues to reappear in various forms around the world, and it can be difficult to identify an isolated sample of a new variant. When the variant is discovered, Gilead applies to the CDC for a special permit to ship it to its Foster City labs.
Once received, it is examined by trained laboratory personnel from both the Clinical and Discovery Virology teams in a specialized biosafety lab built in 2020 for the study of SARS-CoV-2. They examine how virus samples react when exposed to various levels of COVID-19 therapeutics. If the amount of therapeutics required to inhibit the virus does not change, this indicates that the drug retains its full activity against the new variant in a laboratory setting. This method was used to test all of the major prior variants as well as the more recent Omicron BA.4 and BA.5 subvariants.
To speed up the testing process, the researchers are now working on a method that will allow them to create an engineered version of a variant in the lab using available genetic sequencing data. These 'replicons' are an important alternative method for testing COVID-19 therapeutics against novel 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. We need to continue to monitor these variants and generate antiviral data for potential future variants of concern.”