A Deceitful Handshake. In Art of Science

Caption: Ever wondered how SARS-CoV-2 latches onto human cells? Computer simulations capture the atomic-level details of this deadly encounter leading to infection. Participant category: Postdoc Department: Chemistry and Biochemistry The image shows the atom-by-atom reconstruction of the interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, spherical particle coming from above) and the angiotensin-converting enzyme 2 (ACE-2, depicted with yellow and red cartoons) exposed on the host cell plasma membrane (flat lipid bilayer on the bottom). The virus utilizes a prominent glycoprotein, called spike (colored in gray), to latch onto ACE-2. This encounter complex allows the virus to gain entry into and infect the host cell, thus appearing like a “deceitful handshake”. At the Amaro lab, in the Chemistry and Biochemistry department at UCSD, we have been using biophysics and high-performance computing to fight COVID-19. As shown in this image, our effort culminated with the building of the all-atom SARS-CoV-2 viral envelope model, a system bearing over 300 million atoms integrating multiple cryoEM, cryoET, glycomic and lipidomic data. Molecular dynamics simulations of this system will usher in new opportunities for drug and vaccine design and enable the investigation of viral infection at subcellular scales. (References: Casalino L, Gaieb Z et al., Beyond Shielding: The Roles of Glycans in the SARS-CoV-2 Spike Protein. ACS Cent. Sci. 2020; Casalino L, Dommer AC, Gaieb Z, et al., AI-driven multiscale simulations illuminate mechanisms of SARS-CoV-2 spike dynamics. BioRxiv 2020).