Carlos Simmerling (Marsha Laufer Endowed Professor and Associate Director, Laufer Center for Physical & Quantitative Biology, Department of Chemistry, Stony Brook University)
The coronavirus spike is a class I viral fusion glycoprotein that extends from the viral surface and is responsible for viral entry into the host cell. Cryo-EM experiments have revealed spike structures in a variety of states, including the free and bound pre-fusion spike containing both S1 and S2 subunits, as well as the post-fusion S2-only state that adopts a dramatically different conformation. However, little is known about the sequence of conformational changes that link these disparate endpoints, and how receptor binding triggers the process. This lack of detail impedes development of mechanism-based therapeutics targeting the highly conserved fusion machinery. This talk will present an analysis of key spike features across > 500 experimental structures, and all-atom spike simulations involving over 1 million atoms. These computational models were used to guide new cryo-EM experiments that were able to capture the SARS-CoV-2 spike in a conformational state that has not previously been reported.