Newswise – LOS ALAMOS, New Mexico, March 7, 2022 – New computer models and simulations from Los Alamos National Laboratory show researchers how the virus that causes COVID-19 manages to use its spike protein to fuse and infect human cells. Presented at the March meeting of the American Physical Society, atomistic-level imaging is highly consistent with cryo-electron microscopy data, despite the severe challenges of imaging at such high resolution.
“A better understanding of COVID-19 virus entry and spike protein structure will help clarify the mechanism of COVID-19 infection, the effect of variants, aid in vaccine optimization and will help design drugs for treatment,” said Karissa Sanbonmatsu, a Los Alamos structural biologist on the project. Developing a digital twin of the extremely tiny but important structures allows researchers to explore potential techniques for blocking infection at the source.
Why choose this little piece of the cob to study? COVID-19 infections require the virus to enter human host cells, and the spike protein plays a key role in that process, Sanbonmatsu said. In fact, the many variants of the coronavirus, including delta and omicron, have multiple mutations in the spike protein.
One step of virus entry is called virus-cell fusion, where the coronavirus actually fuses with the human host cell. This is not well understood, especially the region of the virus spike protein called the fusion peptide region. The fusion region is believed to be very dynamic and difficult to image at high resolution with conventional techniques such as cryo-electron microscopy and X-ray crystallography.
“Because the spike protein fusion region mediates virus-cell fusion and facilitates virus entry into the cell,” said Chang-Shung Tung, a research partner, “this study provides mechanistic data that can be useful in understanding variants and improving vaccines and treatments.
Using the Chicoma computing platform, one of the Los Alamos supercomputers, Los Alamos researcher Tung created 3D structural models of this region, and Sanbonmatsu performed molecular simulations, creating a set of 3D structures highly consistent with cryo-electron microscopy data, providing some of the first 3D images of the fusion region in atomistic detail.
“The spike protein goes through a lot of twists and turns during viral entry, which makes it difficult to visualize,” Tung said. “Building on data from other viruses, we used 3D modeling to capture regions of the spike that people had never seen before.”
The paper: To be published, following a presentation at the March meeting of the American Physical Society.
Funding: LANL LDRD
On Los Alamos National Laboratory
Los Alamos National Laboratory, a multidisciplinary research institution engaged in strategic science on behalf of national security, is operated by Triad, a public service-focused national security science organization equally owned by its three founding members. : the Battelle Memorial Institute (Battelle), the Texas A&M University System (TAMUS), and the University of California (UC) Regents for the Department of Energy’s National Nuclear Security Administration.
Los Alamos strengthens national security by ensuring the safety and reliability of America’s nuclear stockpile, developing technologies to reduce threats from weapons of mass destruction, and addressing issues related to energy, environment, infrastructure, to global health and security issues.