Los Alamos National Laboratory

Simulations reveal how dominant SARS-CoV-2 strain binds to host, succumbs to antibodies

Dominant G-form Spike protein ‘puts its head up’ more frequently to latch on to receptors, but that makes it more vulnerable to neutralization

Newswise — LOS ALAMOS, N.M., April 16, 2021 — Large-scale supercomputer simulations at the atomic level show that the dominant G form variant of the COVID-19-causing virus is more infectious partly because of its greater ability to readily bind to its target host receptor in the body, compared to other variants. These research results from a Los Alamos National Laboratory–led team illuminate the mechanism of both infection by the G form and antibody resistance against it, which could help in future vaccine development. 

“We found that the interactions among the basic building blocks of the Spike protein become more symmetrical in the G form, and that gives it more opportunities to bind to the receptors in the host — in us,” said Gnana Gnanakaran, corresponding author of the paper published today in Science Advances. “But at the same time, that means antibodies can more easily neutralize it. In essence, the variant puts its head up to bind to the receptor, which gives antibodies the chance to attack it.”

Researchers knew that the variant, also known as D614G, was more infectious and could be neutralized by antibodies, but they didn’t know how. Simulating more than a million individual atoms and requiring about 24 million CPU hours of supercomputer time, the new work provides molecular-level detail about the behavior of this variant’s Spike. 

Current vaccines for SARS-CoV-2, the virus that causes COVID-19, are based on the original D614 form of the virus. This new understanding of the G variant — the most extensive supercomputer simulations of the G form at the atomic level — could mean it offers a backbone for future vaccines. 

The team discovered the D614G variant in early 2020, as the COVID-19 pandemic caused by the SARS-CoV-2 virus was ramping up. These findings were published in Cell. Scientists had observed a mutation in the Spike protein. (In all variants, it is the Spike protein that gives the virus its characteristic corona.) This D614G mutation, named for the amino acid at position 614 on the SARS-CoV-2 genome that underwent a substitution from aspartic acid, prevailed globally within a matter of weeks. 

The Spike proteins bind to a specific receptor found in many of our cells through the Spike’s receptor binding domain, ultimately leading to infection. That binding requires the receptor binding domain to transition structurally from a closed conformation, which cannot bind, to an open conformation, which can. 

The simulations in this new research demonstrate that interactions among the building blocks of the Spike are more symmetrical in the new G-form variant than those in the original D-form strain. That symmetry leads to more viral Spikes in the open conformation, so it can more readily infect a person.

A team of postdoctoral fellows from Los Alamos — Rachael A. Mansbach (now assistant professor of Physics at Concordia University), Srirupa Chakraborty, and Kien Nguyen — led the study by running multiple microsecond-scale simulations of the two variants in both conformations of the receptor binding domain to illuminate how the Spike protein interacts with both the host receptor and with the neutralizing antibodies that can help protect the host from infection. The members of the research team also included Bette Korber of Los Alamos National Laboratory, and David C. Montefiori, of Duke Human Vaccine Institute.

The team thanks Paul Weber, head of Institutional Computing at Los Alamos, for providing access to the supercomputers at the Laboratory for this research. 

The Paper: “The SARS-CoV-2 Spike variant D614G favors an open conformational state,” Science Advances.  Rachael A. Mansbach, Srirupa Chakraborty, Kien Nguyen, David C. Montefiori, Bette Korber, S. Gnanakaran.  DOI: 10.1126/sciadv.abf3671 

The Funding: The project was supported by Los Alamos Laboratory Directed Research and Development project 20200706ER, Director’s Postdoctoral fellowship, and the Center of Nonlinear Studies Postdoctoral Program at Los Alamos. 

About Los Alamos National Laboratory (www.lanl.gov) 
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.

LA-UR-21-23641

SEE ORIGINAL STUDY




Filters close

Showing results

110 of 5612
Released: 11-May-2021 3:55 PM EDT
Pregnant Women Hospitalized for Covid-19 Infection Do Not Face Increased Risk of Death
University of Maryland Medical Center

Pregnant women who develop severe COVID-19 infections that require hospitalization for pneumonia and other complications may not be more likely to die from these infections than non-pregnant women. In fact, they may have significantly lower death rates than their non-pregnant counterparts.

Released: 11-May-2021 3:45 PM EDT
This stinks: New research finds sense of smell and pneumonia linked
Michigan State University

An acute loss of smell is one of the most common symptoms of COVID-19, but for two decades it has been linked to other maladies among them Parkinson’s disease and dementia. Now, a poor sense of smell may signify a higher risk of pneumonia in older adults, says a team of Michigan State University researchers.

Released: 11-May-2021 3:15 PM EDT
How to predict severe influenza in hospitalised patients
University of Melbourne

Published today in Nature Communications, the team from the Peter Doherty Institute for Infection and Immunity (Doherty Institute), Alfred Health and Monash University sought to understand which patients would recover quickly from influenza and which would become severely ill.

Newswise: Five benefits of getting a COVID-19 vaccine
Released: 11-May-2021 2:50 PM EDT
Five benefits of getting a COVID-19 vaccine
University of Alabama at Birmingham

UAB experts explain some of the benefits of getting a COVID-19 vaccine.

Newswise: Covid-19 Alters Gray Matter Volume in the Brain, New Study Shows
Released: 11-May-2021 2:05 PM EDT
Covid-19 Alters Gray Matter Volume in the Brain, New Study Shows
Georgia Institute of Technology

Study led by researchers at Georgia State University and Georgia Institute of Technology finds lower gray matter volume in the northern region of the brain is associated with a higher level of disability among Covid-19 patients, even six months after hospital discharge.

Released: 11-May-2021 10:15 AM EDT
How to Win Over Vaccine Skeptics: Live Expert Panel for May 20, 3pm ET
Newswise

How to Win Over Vaccine Skeptics: Live Expert Panel for May 20, 3pm ET

Newswise:Video Embedded simulating-sneezes-and-coughs-to-show-how-covid-19-spreads
VIDEO
Released: 11-May-2021 10:10 AM EDT
Simulating sneezes and coughs to show how COVID-19 spreads
Sandia National Laboratories

Two groups of researchers at Sandia National Laboratories have published papers on the droplets of liquid sprayed by coughs or sneezes and how far they can travel under different conditions. Both teams used Sandia’s decades of experience with advanced computer simulations studying how liquids and gases move for its nuclear stockpile stewardship mission.

Released: 11-May-2021 9:00 AM EDT
COVID-19 Wastewater Testing Proves Effective in New Study
University of Virginia Health System

Wastewater testing is an effective way to identify new cases of COVID-19 in nursing homes and other congregate living settings, and it may be particularly useful for preventing outbreaks in college dormitories, a new University of Virginia study finds.

Newswise: Hackensack Meridian Mountainside Medical Center to Start Post-COVID-19 Rehabilitation Program
Released: 11-May-2021 9:00 AM EDT
Hackensack Meridian Mountainside Medical Center to Start Post-COVID-19 Rehabilitation Program
Hackensack Meridian Health

Mountainside Medical Center will begin a new Post-COVID exercise program designed for those who have had COVID-19 to improve strength, flexibility, endurance and activities of daily living. The program goal is to improve quality of life and promote lifestyle changes through education and exercise.


Showing results

110 of 5612

close
1.17534