ABSTRACT
The SARS-CoV-2 Omicron variant, with 15 mutations in Spike receptor-binding domain (Spike-RBD), renders virtually all clinical monoclonal antibodies against WT SARS-CoV-2 ineffective. We recently engineered the SARS-CoV-2 host entry receptor, ACE2, to tightly bind WT-RBD and prevent viral entry into host cells ("receptor traps"). Here we determine cryo-EM structures of our receptor traps in complex with stabilized Spike ectodomain. We develop a multi-model pipeline combining Rosetta protein modeling software and cryo-EM to allow interface energy calculations even at limited resolution and identify interface side chains that allow for high-affinity interactions between our ACE2 receptor traps and Spike-RBD. Our structural analysis provides a mechanistic rationale for the high-affinity (0.53-4.2 nM) binding of our ACE2 receptor traps to Omicron-RBD confirmed with biolayer interferometry measurements. Finally, we show that ACE2 receptor traps potently neutralize Omicron and Delta pseudotyped viruses, providing alternative therapeutic routes to combat this evolving virus.
Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Humans , SARS-CoV-2 , Antibodies, Monoclonal , Protein Binding , Antibodies, NeutralizingABSTRACT
Objective: Lassa fever is endemic in West Africa, causing about 5 000 deaths every year. With the increasing trade and travel between China and Africa, the probability of importation of Lassa fever from Africa to China is on the rise. This study aims to access the risk of importation of Lassa fever into China in the next five years.
ABSTRACT
Objective: To assess the risks of public health emergencies, both the indigenous ones and the imported ones, which might occur in the mainland of China in January 2020.