Science Signaling

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for strategies to rapidly develop neutralizing monoclonal antibodies that can function as prophylactic and therapeutic agents and to help guide vaccine design. Here, we demonstrate that engineering approaches can be used to refocus an existing antibody that neutralizes one virus but not a related virus. Through a rapid affinity maturation strategy, we engineered CR3022, a SARS-CoV-1–neutralizing antibody, to bind to the receptor binding domain of SARS-CoV-2 with >1000-fold increased affinity. The engineered CR3022 neutralized SARS-CoV-2 and provided prophylactic protection from viral challenge in a small animal model of SARS-CoV-2 infection. Deep sequencing throughout the engineering process paired with crystallographic analysis of engineered CR3022 elucidated the molecular mechanisms by which the antibody can accommodate sequence differences in the epitopes between SARS-CoV-1 and SARS-CoV-2. This workflow provides a blueprint for the rapid broadening of neutralization of an antibody from one virus to closely related but resistant viruses.

Arginine methylation is prevalent throughout the proteome and regulates the localization and function of splicing and RNA transport factors.

Staphylococcus -derived d -amino acids reduce innate immune responses in the nasal epithelium by stimulating the sweet taste receptor.

Phosphorylated ZO-1 relocalizes from tight junctions to lamellae to associate with α ₅ integrin and control migration.

The signal to move or proliferate diverges at RAF1.

Neurotrophins stimulate calcium signaling to promote axon specification.

Blood vessel leakiness can be induced through the co-receptor NRP1 independently of VEGFR.

Combined therapies targeting the unfolded protein stress response might be a way to treat glioblastomas.

Altered microRNA production in cancer promotes cell proliferation, migration, survival, and adaptation to new environments.

Created with both in vitro and in vivo data, NetPhorest is an atlas of consensus sequence motifs for 179 kinases and 104 phosphorylation-dependent binding domains and reveals new insight into phosphorylation-dependent signaling.