As part of Advancing Drug Discovery: A Webinar Series of the National Academies of Sciences, Engineering and Medicine, the talk titled “Protein Data Bank: From two epidemics & the global pandemic to mRNA vaccines & Paxlovid” will be featured. The 60-minute session will consist a presentation from Dr. Stephen K. Burley, M.D., D.Phil., University Professor and Henry Rutgers Chair at Rutgers and a Q+A session.
Structural biologists around the world and the Protein Data Bank (PDB) played decisive roles in combating the COVID-19 pandemic. This talk will explain how global three-dimensional (3D) biostructure data was turned into global knowledge, allowing scientists and engineers around the world to understand the inner workings of coronaviruses and develop effective SARS-CoV-2 counter measures. State-of-the-art mRNA vaccines, initially designed with guidance from single-particle cryo-electron microscopy structures of the SARS-CoV and MERS-CoV Spike Proteins, benefited more than five billion individuals around the world by preventing infections entirely or significantly reducing morbidity and mortality. Structure-guided drug discovery efforts at Pfizer, first initiated in the 2000s in response to SARS-CoV and reactivated in 2020 early in the global pandemic, yielded nirmatrelvir — a potent inhibitor of the SARS-CoV-2 Main Protease. This targeted antiviral drug received Emergency Use Authorization from the United States Food and Drug Administration in December 2021, less than two years following public release of the viral genome sequence. It is used clinically for the treatment of acute SARS-CoV-2 infections in a fixed dose combination with ritonavir and sold under the brand name Paxlovid. Bolstered by open access to research data generated with public and private monies, particularly 3D structures of coronavirus proteins archived in the PDB, basic and applied researchers made a difference when the world desperately needed them to succeed. To underscore the importance of these contributions, I quote Dr. Anthony Fauci, former head of the National Institute of Allergy and Infectious Disease, “Show me a person who’s vaccinated, got infected, took Paxlovid and died. I can’t find anybody.”
Stephen Kevin Burley is an expert in structural biology, biophysics, computational biology, data science, structure/fragment-based drug discovery, and clinical medicine/oncology. Burley is the Director of the RCSB Protein Data Bank (rcsb.org). Within Rutgers, The State University of New Jersey he serves as University Professor and Henry Rutgers Chair, Founding Director of the Institute for Quantitative Biomedicine, and a Member of the Rutgers Cancer Institute of New Jersey, wherein he Co-Leads the Cancer Pharmacology Research Program.
