Scientists create 'all-atom' model of SARS-CoV-2 spike protein

By Angela Betsaida B. Laguipo, BSNJun 23 2020

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the coronavirus disease (COVID-19), an illness that has spread across the globe, infecting more than 9 million people. The novel coronavirus invades cells through "spike proteins," which sticks and binds itself to a host cell.

Now, a team of researchers at Lehigh University, Seoul National University, and the University of Cambridge have managed to map out every single atom in the spike proteins, including performing simulations on NURION, the largest supercomputer in South Korea at KRISTI (Korean Institute of Science and Technology Information).

The team believes that mapping every single atom in the spike protein is essential to better understand its role in viral entry into cells, which makes it the primary target for developing a vaccine or an antiviral drug against COVID-19.

A model of an S-protein. Illustration: Dr. Yeolkyo Choi/Lehigh

What are spike proteins?

The S protein is a highly glycosylated type I transmembrane fusion protein made up of about 1,160 to 1,400 amino acids, depending on the type of the virus. The presence of S proteins on coronaviruses, such as SARS-CoV-2, SARS-CoV (severe acute respiratory syndrome coronavirus), and the MERS-CoV (Middle East respiratory syndrome coronavirus), is what generates the spike-shaped protrusions found on their surface.

The "spike protein or S protein" is the major surface protein the virus uses to bind to a receptor, the angiotensin-converting enzyme 2 (ACE2), which is another protein that acts as a doorway into a human cell. Many therapies and vaccines were being based on preventing the attachment and fusion of these two receptors.

First open-source all-atom models of S protein

The scientists produced the first open-source all-atom models of a full-length spike protein of the SARS-CoV-2 that facilitates entry into host cells.

A professor in Lehigh's Department of Biological Sciences and Bioengineering Department, Wonpil Im, developed the CHARMM-GUI.

First described in the Journal of Physical Chemistry B., CHARMM-GUI is a program that simulates complex biomolecular systems accurately and quickly. It is termed as a computational microscope that helps shed light on the molecular-level interactions that cannot be observed or studied in any other way.

The model-building program is open access and can be found on the website page of CHARMM-GUI. In the same source, the scientists shared a video illustrating how to build the membrane system from their SARS-CoV-2 S protein models.

"Our models are the first fully-glycosylated full-length SARS-CoV-2 spike (S) protein models that are available to other scientists. I was fortunate to collaborate with Dr. Chaok Seok from Seoul National University in Korea and Dr. Tristan Croll from the University of Cambridge in the U.K. Our team spent days and nights to build these models very carefully from the known cryo-EM structure portions. Modeling was very challenging because there were many regions where simple modeling failed to provide high-quality models," Wonpil Im explained.

To arrive at their findings, the researchers first modeled the missing amino acid residues and other missing domains. Further, they modeled all glycans that are attached to the spike protein, which are molecules that can prevent antibody recognition.

New therapies and vaccine

Gaining more understanding about the coronavirus and its structure can help scientists find an effective vaccine or drug to combat the spreading infection. The researchers suggest that the data gathered on the spike protein's atoms can be used to develop therapies that specifically target the coronavirus on the atomic level, making them more effective.

Finding an effective vaccine and drug for the coronavirus is crucial amid the pandemic, which has spread across 188 countries and territories. So far, the virus has caused more than 472,000 deaths.

The United States and Brazil report the highest number of confirmed cases, with more than 2.32 million and 1.10 million cases, respectively. The United States has the highest death toll of at least 120,000 deaths, while Brazil reports more than 51,000 deaths.

Many countries have already lifted lockdown measures, slowly returning to normal despite the growing number of cases. The coronavirus pandemic has taken a toll on economies worldwide, prompting governments to open businesses slowly. With more people outside their homes, the virus may spread rapidly, causing more infections. Finding a vaccine and drug to treat the infection is crucial to prevent more deaths.