September 24, 2024
A groundbreaking discovery in the fight against COVID-19 has been made by a team led by Paul Whitford from Northeastern University and Jose Onuchic from Rice University, both prominent researchers at the National Science Foundation Physics Frontiers Center at the Center for Theoretical Biological Physics (CTBP).
Paul Whitford, Professor, Department of Physics, Northeastern University
In partnership with Walter Mothes and Wenwei Li of Yale University, the team has revealed new insights into how SARS-CoV-2, the virus behind COVID-19, invades human cells and how it can be stopped. This vital research, which uncovers the virus’s infection mechanisms and paves the way for future treatments, was published in Science.
Summary of the Research
At the start of the pandemic, researchers at the Center for Theoretical Biological Physics (CTBP) began to develop novel theoretical models that could be used to understand the fundamental molecular factors that control infection by the SARS-CoV-2, the virus that causes COVID. To this end, researchers leveraged their understanding of protein folding in order to perform the first simulations that could elucidate how the virus is able to enter a cell (Dodero-Rojas, Onuchic and Whitford, eLife, 2021). Later, imaging techniques were developed by the Mothes Laboratory at Yale University, which confirmed the theoretically predicted dynamics!
Inspired by this success, our groups have since collaborated to understand how novel antibodies can stop the virus (Grunst et al. Science, 2024).
In parallel to these efforts, we have also used high-performance computing and theoretical models to help develop a new vaccine-delivery platform (Staquicini et al. Proceedings of the National Academy of Sciences, 2021).
Together, these studies provide a physical-chemical foundation that can enable development of next-generation vaccines that are effective against current and future strains of SARS-CoV-2.
Significance of the Discovery
This research sheds light on the intricate process of viral entry into human cells and highlights the potential to target the conserved S2 domain of the spike protein—a breakthrough that could lead to vaccines effective against multiple strains of COVID-19. By combining theoretical modeling with experimental validation, the team has unlocked new opportunities to neutralize the virus before it infects cells.
“Our work demonstrates the power of combining simulations with real-world imaging,” said Onuchic. “It opens doors for designing treatments that can stop not just COVID-19, but future coronaviruses as well.”
Potential Impact on Future Vaccines and Treatments
The discovery of how antibodies can prevent SARS-CoV-2 from entering human cells, alongside the development of a novel vaccine-delivery platform, has the potential to revolutionize how we approach pandemic preparedness. By targeting the stable S2 domain, researchers could create vaccines and therapies that remain effective as the virus mutates, offering long-term protection against a wide range of coronavirus strains.
“These studies provide a physical-chemical foundation that can drive the creation of next-generation vaccines” said Whitford. “The goal is to stay ahead of viral evolution, protecting against future outbreaks.”
This groundbreaking research, supported by the National Science Foundation, National Institutes of Health, and other global institutions, has positioned the scientific community to not only fight COVID-19 more effectively but also to be ready for the next viral threat.