Early in the COVID-19 pandemic, it was quickly established that the receptor binding domain (RBD) of the SARS-CoV-2 spike protein is a prime target for neutralizing antibodies. Now, scientists have found a second region of the spike protein that is targeted by dozens of antibodies, some of which exhibit ultrapotent neutralizing activity. Read more »
Guiding Target Selection for COVID-19 Antibody Therapeutics
Protein-structure studies helped demonstrate that the primary target of antibody-based COVID-19 immunity is the part of the virus’s spike protein that can most easily mutate. The work anticipated the rise of SARS-CoV-2 variants and guides the selection of antibody therapeutics that are likely to be more resistant to immune escape. Read more »
Mystery Protein Helps COVID‑19 Avoid Immunity
Using the Advanced Light Source (ALS), researchers solved the structure of ORF8, a protein specific to SARS-CoV-2. Understanding the structure of ORF8 opens the door to therapy studies targeting SARS-CoV-2, the virus responsible for causing COVID-19. Read more »
The Odd Structure of ORF8: Scientists Map the Coronavirus Protein Linked to Immune Evasion and Disease Severity
Researchers determined the atomic structure of a coronavirus protein thought to help the pathogen evade and dampen response from human immune cells. Researchers determined the atomic structure of a coronavirus protein thought to help the pathogen evade and dampen response from human immune cells. Read more »
Targeting the trypanosome kinetochore with CLK1 protein kinase inhibitors
Saldivia et al. identify CLK1 as the target for the amidobenzimidazoles series of compounds. Inhibition of this protein kinase impairs inner kinetochore recruitment, causing cell-cycle arrest and cell death in trypanosomal pathogens such as Trypanosoma brucei. Read more »
Missing Lysine Link Could Improve Plant-Based Nutrition
To engineer crops with higher levels of the important amino acid, lysine, researchers solved the structure of an enzyme that helps break down lysine in plants. A fuller understanding of the factors affecting lysine levels should aid in the successful development of stable high-lysine crops to combat malnutrition globally. Read more »
Structural Features Mediating Zinc Binding and Transfer in the AztABCD Zinc Transporter System
Zinc homeostasis is critical for bacterial survival and virulence. Extracellular zinc-binding proteins play an important role in this process. This work assesses the role of several flexible or unstructured sequences in zinc binding and transfer from proteins AztD to AztC. The results provide insights into the dynamic nature of these processes and support a previously proposed structural model of transfer. Read more »
Rotavirus VP3 Is a Multifunctional Capping Machine
Rotavirus, a major cause of infantile gastroenteritis, is responsible for the deaths of about 200,000 children per year. Although vaccines are available, the virus still circulates, and a fuller understanding of the viral structures is needed. Here, scientists investigate the structure and function of the last unsolved rotavirus structural protein. Read more »
Evaluation of Free Energy Calculations for the Prioritization of Macrocycle Synthesis
Free energy perturbation methods represent a paradigm shift in drug discovery, where computational methods inform benchtop activities. Macrocycles are highly constrained molecules, often resulting in nonintuitive structure–activity relationships requiring lengthy synthetic routes. Free energy perturbation methods can be used to predict potency, guiding synthetic chemistry efforts to de-risk complex synthesis. Read more »
Antibody from SARS Survivor Neutralizes SARS-CoV-2
Using structural data from the ALS and cryo-electron microscopy, researchers have characterized how an antibody binds to and neutralizes SARS-CoV-2. This work provides the basis for therapeutic and vaccine development for the SARS-CoV-2 virus, which is responsible for the COVID-19 pandemic. Read more »
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