Peptidomimetics as potent dual SARS-CoV-2 cathepsin-L and main protease inhibitors: In silico design, synthesis and pharmacological characterization

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 266, P. 116128 - 116128

Published: Jan. 9, 2024

In this paper we present the design, synthesis, and biological evaluation of a new series peptidomimetics acting as potent anti-SARS-CoV-2 agents. Starting from our previously described Main Protease (M

Language: Английский

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Increased Incidence of Ventilator-Acquired Pneumonia in Coronavirus Disease 2019 Patients: A Multicentric Cohort Study*

Critical Care Medicine, Journal Year: 2021, Volume and Issue: 50(3), P. 449 - 459

Published: Sept. 22, 2021

OBJECTIVES: Little is known about the epidemiology of ventilator-acquired pneumonia among coronavirus disease 2019 patients such as incidence or etiological agents. Some studies suggest a higher risk ventilator-associated in this specific population. DESIGN: Cohort exposed/nonexposed study REA-REZO surveillance network. SETTING: Multicentric; ICUs France. PATIENTS: The at admission were matched on age, sex, center inclusion, presence antimicrobial therapy admission, patient provenance, time from ICU to mechanical ventilation, and Simplified Acute Physiology Score II included between 2016 within same network (1:1). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: overall pneumonia, cumulative incidence, hazard rate first second estimated. In addition, microbiological ecology resistant pattern exposed nonexposed compared. Medication data not collected. A total 1,879 each group. was (25.5; 95% CI [23.7–27.45] vs 15.4; [13.7–17.3] per 1,000 ventilation days). for (respective Gray test p < 0.0001 0.0167). resistance comparable groups with predominance Enterobacterales nonfermenting Gram-negative bacteria. documented similar groups, except lower methicillin-resistant Staphylococcus aureus (6% 23%; = 0.013). CONCLUSIONS: There occurring compared general population, pattern.

Language: Английский

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Purification and characterization of the receptor‐binding domain of SARS‐CoV‐2 spike protein from Escherichia coli

Engineering in Life Sciences, Journal Year: 2021, Volume and Issue: 21(6), P. 453 - 460

Published: May 7, 2021

Abstract SARS‐CoV‐2 is responsible for a disruptive worldwide viral pandemic, and renders severe respiratory disease known as COVID‐19. Spike protein of mediates entry into host cells by binding ACE2 through the receptor‐binding domain (RBD). RBD an important target development virus inhibitors, neutralizing antibodies, vaccines. expressed in mammalian suffers from low expression yield high cost. E. coli popular expression, which has advantage easy scalability with However, (RBD‐1) lacks glycosylation, its antigenic epitopes may not be sufficiently exposed. In present study, RBD‐1 was purified Ni Sepharose Fast Flow column. structurally characterized compared HEK293 (RBD‐2). The secondary structure tertiary were largely maintained without glycosylation. particular, major β‐sheet content almost unaltered. could strongly bind dissociation constant (K D ) 2.98 × 10 –8 M. Thus, expected to apply vaccine development, screening drugs test kit.

Language: Английский

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Impact of SARS‐CoV‐2 Infection (COVID‐19) on Cytochromes P450 Activity Assessed by the Geneva Cocktail

Clinical Pharmacology & Therapeutics, Journal Year: 2021, Volume and Issue: 110(5), P. 1358 - 1367

Published: Sept. 2, 2021

Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, is a with an underlying inflammatory state. We have previously demonstrated that inflammation modulates cytochromes P450 (CYPs) activity in isoform‐specific manner. therefore hypothesized COVID‐19 might also impact CYP activity, and thus aimed to evaluate the of context SARS‐CoV‐2 infection on six main human CYPs activity. This prospective observational study was conducted 28 patients hospitalized at Geneva University Hospitals (Switzerland) diagnosis moderate COVID‐19. They received phenotyping cocktail orally during first 72 hours hospitalization after 3 months. Capillary blood samples were collected administration assess metabolic ratios (MRs) CYP1A2, 2B6, 2C9, 2C19, 2D6, 3A. C‐reactive protein (CRP), interleukin 6 (IL‐6), tumor necrosis factor‐α (TNF‐α) levels measured blood. CYP2C19, CYP3A MRs decreased 52.6% ( P = 0.0001), 74.7% 0.0006), 22.8% 0.045), respectively, CYP2B6 CYP2C9 increased 101.1% 0.009) 55.8% respectively. CYP2D6 MR variation did not reach statistical significance 0.072). As expected, good model as mean serum CRP, IL‐6, TNF‐α significantly < 0.001) higher infection. are modulated manner The pharmacokinetics substrates, whether used treat or usual treatment patients, could be clinically impacted.

Language: Английский

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Implication of SARS-CoV-2 Immune Escape Spike Variants on Secondary and Vaccine Breakthrough Infections

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Nov. 3, 2021

COVID-19 pandemic remains an on-going global health and economic threat that has amassed millions of deaths. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent this disease constantly under evolutionary pressures drive modification its genome which may represent a to efficacy current vaccines available. This article highlights facilitate rise new SARS-CoV-2 variants key mutations viral spike protein – L452R, E484K, N501Y D614G– promote immune escape mechanism warrant cautionary point for clinical public responses in terms re-infection, vaccine breakthrough infection therapeutic values.

Language: Английский

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