D614G Mutation Makes SARS-CoV-2 Up to Eight Times More Infectious than Initial Virus that Originated in China

The D614G mutation in the SARS-CoV-2 spike protein - commonly referred to as the “G variant” - likely emerged in early 2020 and is now is the most prevalent and dominant form of the SARS-CoV-2 virus in many countries around the globe. With multiple mutations circulating, researchers have been working to understand the functional significance of these mutations and whether they meaningfully change how infectious or deadly the virus is. In the latest study, the researchers introduced a virus with the D614G mutation into human lung, liver, and colon cells. They also introduced the “wild type” version of the coronavirus - the version of the virus without the mutation found early on in the pandemic - into these same cell types for comparison.

They found that the D614G variant increased transduction, or transmissibility, of the virus up to eight-fold as compared to the original virus. The researchers also found that the spike protein mutation made the virus more resistant to being cleaved or split by other proteins. This provides a possible mechanism for the variant’s increased ability to infect cells, as the hardier variant resulted in a greater proportion of intact spike protein per virus. The team’s findings join a growing consensus among scientists that the D614G variant is more infectious, although it is still unclear whether the variant and its rapid spread have a clinical impact on COVID-19 disease progression, as several studies suggest that the D614G variant is not linked to more severe disease or hospitalization.

The researchers note that findings on the increased transmissibility of the D614G variant may influence COVID-19 vaccine development and, in particular, it may be beneficial for future booster shots to include diverse forms of the spike protein from different circulating variants. The vaccines with emergency use authorization from the FDA, as well as those under development, were created using the original spike sequence; studies are underway to understand how well these vaccines protect against the variants that emerged in the UK, South Africa, and Brazil, all of which contain the D614G mutation. Recent work from other groups suggests that initial vaccines with the D614 form of spike can protect against the newer G614 form of spike, although more work needs to be done to understand how multiple mutations can interact with each other and impact immune response.

"In the months since we initially conducted this study, the importance of the D614G mutation has grown: the mutation has reached near universal prevalence and is included in all current variants of concern," said Neville Sanjana, assistant professor of biology at NYU, assistant professor of neuroscience and physiology at NYU Grossman School of Medicine, and Core Faculty Member at the New York Genome Center. "Confirming that the mutation leads to more transmissibility may help explain, in part, why the virus has spread so rapidly over the past year."

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