Rapid in silico design of antibodies targeting SARS-CoV-2 using machine learning and supercomputing

Thomas Desautels; Adam Zemla; Edmond Lau; Magdalena Franco; Daniel Faissol

A CryoEM-derived structure of the SARS-CoV-2 spike protein became available on Feb. 19, 2020 and was publicly released Feb 26, 2020 [18] (https://www.rcsb.org/structure/6vsb). X-ray crystal structures (of the receptor-binding domain) became available starting March 4, 2020 (http://www.rcsb.org/structure/6VW1 , to be published). Comparison with our homology models indicates that our estimated structures (completed Jan 23, 2020; publicly available beginning Feb 3, 2020) were accurate, especially at the FAB (antigen-binding fragment) [19] antibody interfaces. Figure 1 and Table 1 show residue deviations for our SARS-CoV-2 homology models, SARS-CoV-2 CryoEM structures, and SARS-CoV-1 structures, using a SARS-CoV-2 X-ray structure 6w41_C as the reference. The two regions indicated by rectangular boxes (residues 382-393 and 475-484) are part of loop regions where local conformations deviate, but note that these regions are not part of the interface with the selected antibodies. Figure 2 depicts our homology-based model superimposed on a CryoEM structure, with the M396 antibody structure provided to indicate the FAB-RBD interface region. Note that the only regions with deviations above 2.0 Ã… are outside the interface region.