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Structure-guided engineering of a mutation-tolerant inhibitor peptide against variable SARS-CoV-2 spikes.

Proc Natl Acad Sci U S A

January 2025

Cellular and Structural Physiology Laboratory, Advanced Research Initiative, Institute of Integrated Research, Institute of Science Tokyo, Bunkyo-ku, Tokyo 113-8510, Japan.

Pathogen mutations present an inevitable and challenging problem for therapeutics and the development of mutation-tolerant anti-infective drugs to strengthen global health and combat evolving pathogens is urgently needed. While spike proteins on viral surfaces are attractive targets for preventing viral entry, they mutate frequently, making it difficult to develop effective therapeutics. Here, we used a structure-guided strategy to engineer an inhibitor peptide against the SARS-CoV-2 spike, called CeSPIACE, with mutation-tolerant and potent binding ability against all variants to enhance affinity for the invariant architecture of the receptor-binding domain (RBD).

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A 3-year-old spayed male mixed-breed Labrador presented to the Emergency and Critical Care Unit with lethargy, loss of appetite, vomiting, a recent history of presyncopal episodes, and severe exercise intolerance. On admission, the patient had bradycardia, low blood pressure, and mild abdominal pain. Serum biochemistry information revealed severe hyperkalemia, hyponatremia, hypoglycemia, and mildly increased liver and kidney parameters.

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Background: Bacterial infections in the Intensive Care Units are a threat to the lives of critically ill patients. Their vulnerable immunity predisposes them to developing bacteria-associated sepsis, deteriorating their already fragile health. In the face of increasing antibiotics resistance, the problem of bacterial infection in ICU is worsening.

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Metabolic syndrome is a group of pathological disorders increasing the risk of serious diseases including cardiovascular disease, stroke, type 2 diabetes. Global widespread of the metabolic syndrome has put a heavy social burden. Interestingly, a crucial link between the metabolic syndrome and a psychiatric disorder may frequently coexist, in which certain shared mechanisms might play a role for the pathogenesis.

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Extracellular vesicles, or exosomes, are produced by every type of cell and contain metabolites, proteins, lipids, and nucleic acids. Their role in health and disease is to influence different aspects of cell biology and to act as intermediaries between cells. Follicular fluid exosomes or extracellular vesicles (FF-EVs) secreted by ovarian granulosa cells are critical mediators of ovary growth and maturation.

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