An antibody therapy that appears to neutralize all known SARS-CoV-2 strains, and other coronaviruses, was developed with a little help from structural biologist Jay Nix.
As instruments in large-scale user facilities are becoming more powerful, the volume of data and its complexity also grow. To leverage these heightened capabilities and accelerate scientific discoveries, a field known as autonomous discovery has emerged. It uses algorithms to learn from a comparatively little amount of input data and determine the best next experimental steps — all with minimal human intervention.
Scientists from three national laboratories who specialize in revealing the atomic structure of proteins collaborated to model the complex protein responsible for SARS-CoV-2 replication, revealing potential weak spots for drug development.
Papain-like protease (PLpro) from SARS-CoV-2 plays essential roles in the replication cycle of the virus that is the cause of the global COVID-19 pandemic. In human cells that the virus has infected, PLpro seeks out and binds with the interferon-stimulated gene 15 (ISG15) protein, a key component of the cells’ immune response. PLpro strips ISG15 from other cellular proteins to aid SARS-CoV-2 in evading the body’s immune system.
Scientists at Oak Ridge National Laboratory (ORNL) used small-angle neutron scattering (SANS) at the High Flux Isotope Reactor (HFIR) combined with computational techniques to reveal the molecular details of how the two proteins interact. Susan Tsutakawa, a staff scientist in the Molecular Biophysics and Integrated Bioimaging (MBIB) Division, obtained small-angle x-ray scattering (SAXS) data on the PLpro-ISG15 complex at Berkeley Lab’s Advanced Light Source (ALS) to augment the SANS work.
Scientists at the Berkeley Center for Structural Biology contributed resources and data to a recently-published study revealing a new site on the coronavirus spike protein used by antibodies to block the invasion of the virus into healthy cells. The discovery of this new antibody binding site will help scientists as they work to continue improving treatment and vaccine formulations for COVID-19 and its variants.