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Los Alamos National Laboratory

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Tracking SARS-CoV-2 Spike mutations

A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic. 

TRACKING SARS-COV-2 SPIKE MUTATIONS  

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Newer variant of COVID-19–causing virus dominates global infections

Virus with D614G change in Spike out-competes original strain, but may not make patients sicker

 

LOS ALAMOS, N.M., July 2, 2020— Research out today in the journal Cell shows that a specific change in the SARS-CoV-2 coronavirus virus genome, previously associated with increased viral transmission and the spread of COVID-19, is more infectious in cell culture. The variant in question, D614G, makes a small but effective change in the virus’s ‘Spike’ protein, which the virus uses to enter human cells.

Bette Korber, a theoretical biologist at Los Alamos National Laboratory and lead author of the study, noted, “The D614G variant first came to our attention in early April, as we had observed a strikingly repetitive pattern. All over the world, even when local epidemics had many cases of the original form circulating, soon after the D614G variant was introduced into a region it became the prevalent form.”

Geographic information from samples from the GISAID COVID-19 viral sequence database enabled tracking of this highly recurrent pattern, a shift in the viral population from the original form to the D614G variant. This occurred at every geographic level: country, subcountry, county, and city.    
       
Two independent lines of experimental evidence that support these initial results are included in today’s paper. These additional experiments, led by Professor Erica Ollmann Saphire, Ph.D., at the La Jolla Institute, and by Professor David Montefiori, Ph.D., at Duke University, showed that the D614G change increases the virus’s infectivity in the laboratory. These new experiments, as well as more extensive sequence and clinical data and improved statistical models, are presented in the Cell paper. More in vivo work remains to be done to determine the full implications of the change.

The SARS-CoV-2 virus has a low mutation rate overall (much lower than the viruses that cause influenza and HIV-AIDS). The D614G variant appears as part of a set of four linked mutations that appear to have arisen once and then moved together around the world as a consistent set of variations.

“It’s remarkable to me,” commented Will Fischer of Los Alamos, an author on the study, “both that this increase in infectivity was detected by careful observation of sequence data alone, and that our experimental colleagues could confirm it with live virus in such a short time.”

Fortunately, “the clinical data in this paper from Sheffield showed that even though patients with the new G virus carried more copies of the virus than patients infected with D, there wasn’t a corresponding increase in the severity of illness," said Saphire, who leads the Gates Foundation-supported Coronavirus Immunotherapy Consortium (CoVIC).

Korber noted, “These findings suggest that the newer form of the virus may be even more readily transmitted than the original form – whether or not that conclusion is ultimately confirmed, it highlights the value of what were already good ideas: to wear masks and to maintain social distancing.”

Research partners from Los Alamos National Laboratory, Duke University, and the University of Sheffield initially published work on this analysis on the bioRxiv site in an April 2020 preprint. That work also included observations of COVID-19 patients from Sheffield that suggested an association of the D614G variant with higher viral loads in the upper respiratory tract.

“It is possible to track SARS-CoV-2 evolution globally because researchers worldwide are rapidly making their viral sequence data available through the GISAID viral sequence database”, Korber said. Currently tens of thousands of sequences are available through this project, and this enabled Korber and the research team to identify the emergence of the D614G variant.

GISAID was established to encourage collaboration among influenza researchers, but early in the epidemic the consortium established a SARS-CoV-2 database, which soon became the de facto standard for sharing outbreak sequences among researchers worldwide.
 
The study, "Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus" (DOI: 10.1016/j.cell.2020.06.043) was supported by the Medical Research Council (MRC) part of UK Research & Innovation (UKRI the National Institute of Health Research (NIHR); Genome Research Limited, operating as the Wellcome Sanger Institute;  CoVIC, INV-006133 of the COVID-19 Therapeutics Accelerator, supported by the Bill and Melinda Gates Foundation, Mastercard, Wellcome; private philanthropic support, as well as the Overton family; a FastGrant, from Emergent Ventures, in aid of COVID-19 research; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Interagency Agreement No. AAI12007-001-00000, and the Los Alamos Laboratory Directed Research and Development program.
 
Additional study authors included S. Gnanakaran, H. Yoon, J. Theiler, W. Abfalterer, N. Hengartner, E.E. Giorgi, T. Bhattacharya, B. Foley, K.M. Hastie, M.D. Parker, D.G. Partridge, C.M. Evans, T.M. Freeman, T.I. de Silva, C. McDanal, L.G. Perez, H. Tang, A. Moon-Walker, S.P. Whelan, C.C. LaBranche.
 
About Los Alamos National Laboratory
Los Alamos National Laboratory, a multidisciplinary research institution engaged in strategic science on behalf of national security, is managed by Triad, a public service oriented, national security science organization equally owned by its three founding members: Battelle Memorial Institute (Battelle), the Texas A&M University System (TAMUS), and the Regents of the University of California (UC) for the Department of Energy’s National Nuclear Security Administration.

Los Alamos enhances national security by ensuring the safety and reliability of the U.S. nuclear stockpile, developing technologies to reduce threats from weapons of mass destruction, and solving problems related to energy, environment, infrastructure, health, and global security concerns.


Video


Abstract

Tracking SARS-CoV-2 Spike mutations: evidence for increased infectivity of D614G

Summary.  A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic. Dynamic tracking of variant frequencies revealed a recurrent pattern of G614 increase at multiple geographic levels: national, regional and municipal. The shift occurred even in local epidemics where the original D614 form was well established prior to the introduction of the G614 variant. The consistency of this pattern was highly statistically significant, suggesting that the G614 variant may have a fitness advantage. We found that the G614 variant grows to higher titer as pseudotyped virions. In infected individuals G614 is associated with lower RT- PCR cycle thresholds, suggestive of higher upper respiratory tract viral loads, although not with increased disease severity. These findings illuminate changes important for a mechanistic understanding of the virus, and support continuing surveillance of Spike mutations to aid in the development of immunological interventions.



Media

Did a Mutation Help the Coronavirus Spread? More Evidence, but Lingering QuestionsThe New York Times (7/2)
Researchers claim that a predominating variant had a “fitness advantage.” But many experts are not persuaded.

New form of coronavirus spreads feaster, but doesn't make people sickerCNN (7/2)
A global study has found clear evidence that a new form of the coronavirus has spread from Europe to the US. The new mutation makes the virus more infectious but does not seem to make people any sicker, an international team of researchers reported.

This coronavirus mutation has taken over the world. Scientists are trying to understand why. —Washington Post (7/2)
At least five laboratory experiments suggest that the mutation makes the virus more infectious, although only one of those studies has been peer-reviewed. That study, led by scientists at Los Alamos National Laboratory and published Thursday in the journal Cell, also asserts that patients with the G variant actually have more virus in their bodies, making them more likely to spread it to others.

The coronavirus has changed since it left Wuhan. Is it more infectious? Los Angeles Times (7/2)
The study authors, led by Bette Korber, a computational biologist at Los Alamos National Laboratory, posted a preliminary version of the work in May that generated substantial controversy by claiming the mutation in the spike protein made the virus more contagious.

Newer, More Dominant COVID-19 Variant Is More Infectious in the Lab Genetic Engineering & Biotechnology News (7/2)
“The D614G variant first came to our attention in early April, as we had observed a strikingly repetitive pattern," said Bette Korber, the study’s lead author and a theoretical biologist at Los Alamos National Laboratory.