Outbreak

Viral replication

Pathology

Virology

Antibody

Receptor

Chemistry

Immunology

Virus

Coronavirus

Disease

2019-20 coronavirus outbreak

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Coronavirus disease 2019 (COVID-19)

Infectious disease (medical specialty)

Monoclonal antibody

Biochemistry

Viral entry

Medicine

Biology

Vero cell

Cell biology

Science

Miniproteins against SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is decorated with spikes, and viral entry into cells is initiated when these spikes bind to the host angiotensin-converting enzyme 2 (ACE2) receptor. Many monoclonal antibody therapies in development target the spike proteins. Cao et al. designed small, stable proteins that bind tightly to the spike and block it from binding to ACE2. The best designs bind with very high affinity and prevent SARS-CoV-2 infection of mammalian Vero E6 cells. Cryo–electron microscopy shows that the structures of the two most potent inhibitors are nearly identical to the computational models. Unlike antibodies, the miniproteins do not require expression in mammalian cells, and their small size and high stability may allow formulation for direct delivery to the nasal or respiratory system. Science , this issue p. 426

De novo design of picomolar SARS-CoV-2 miniprotein inhibitors