Maynooth University research reveals key vulnerabilities in viral trigger for COVID-19

High-performance computing research at Maynooth University and the University of California San Diego has provided, for the first time, detailed insight into the weaknesses and strengths of the SARS-CoV-2 S protein. SARS-CoV-2 is the strain of coronavirus that causes COVID-19. The research indicates key vulnerabilities in the coronavirus’ spike (S) protein that can be targeted specifically for the rapid development of highly effective therapeutic strategies.

Dr Elisa Fadda in Department of Chemistry and the Hamilton Institute at Maynooth University, and Prof Rommie Amaro at the University of California San Diego, joined forces with their teams to study the unique structure and viral activity of the spike or S protein using high-performance computing (HPC).

Commenting on the research, Dr Elisa Fadda said: “Molecular simulations provide insight into the biomolecular world otherwise unattainable by any other means of investigation. In this research, molecular dynamics simulations provided new detailed insight into the functional role of the glycan shield in the S protein’s architecture, dynamics, stability and activation, thus unveiling its strengths and weaknesses.”

“These results indicate for the first time key vulnerabilities of the SARS-CoV-2 S protein that can be targeted specifically for the rapid development of highly effective therapeutic strategies.”

The primary route of infection from the coronavirus involves the interaction between the S protein, and a receptor called ACE2 on the surface of host cells in our respiratory airways.

The S protein uses a sugary coating of molecules (carbohydrates), called glycans, to camouflage itself as harmless from defending antibodies. These highly flexible glycans shroud the surface proteins from the immune system and, like a shield, allow the virus to reach the host cell undetected.

The S protein’s densely covered layer of complex carbohydrates are too dynamic to be detected by X-ray diffraction or cryo-EM used as standard in structural biology research and are generally invisible.

Molecular simulations provide, for the first time, detailed insight into how the structure of the SARS-CoV-2 S glycan shield not only cloaks the S protein in its inactive, or ‘closed’ form but also rearranges itself to support and reinforce its active ‘open’ structure, due to a ‘lock and load’ mechanism of action.

The study, Shielding and Beyond: The Roles of Glycans in SARS-CoV-2 Spike Protein, was conducted through molecular simulations on the National Science Foundation-funded Frontera supercomputer at the Texas Advanced Computing Centre (TACC), and the Science Foundation Ireland funded Kay supercomputer at the Irish Centre for High-End Computing (ICHEC).