Even though the World Health Organization announced the end of the COVID-19 pandemic as a global public health emergency on May 5, 2023, SARS-CoV-2 continues to pose a significant health threat worldwide, resulting in substantial numbers of infections and fatalities. This study investigated the antiviral potential of Z-FA-FMK (FMK), a novel host cathepsin L protease inhibitor, against SARS-CoV-2 infection using both in vitro and in vivo models. In vitro assessments of FMK against a diverse set of SARS-CoV-2 strains, including the Wuhan-like strain and nine variants, demonstrated potent inhibition with EC values ranging from 0.55 to 2.41 μM, showcasing similar or superior efficacy compared to FDA-approved antivirals nirmatrelvir (NTV) and molnupiravir (MPV). In vivo experiments using orally administered FMK (25 mg/kg) in SARS-CoV-2-infected K18 hACE2 transgenic mice revealed improved survival rates of 60% and accelerated recovery compared to NTV and MPV treatments. Additionally, FMK displayed a longer half-life (17.26 ± 8.89 h) than NTV and MPV in the mouse model. Due to its host-targeting mechanism, FMK offers potential advantages such as reduced drug resistance and broad-spectrum antiviral activity against multiple coronaviruses. These findings indicate that FMK may serve as a promising candidate for further clinical evaluation in the fight against SARS-CoV-2.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.antiviral.2023.105669 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Potency of anti-trematode in inhibiting cathepsin-2L and cathepsin-5L of using homology, docking, and molecular dynamics.
Open Vet J
November 2024
Parasitology Department, Faculty of Veterinary Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia.
Background: Cathepsin-L (FhCL) is a group of enzymes that most flukes express and secreted significantly in parasite-host interactions. Researches are focusing on antigens released by as one of the keys to understanding immunologic pathways in parasite infection and targets for anthelmintics. Efforts to suppress FhCL function through vaccination or therapy using anthelmintic drugs are key factors in controlling field-level trematode infections.
View Article and Find Full Text PDFTranscriptomic profiling of "brain-eating amoeba" infection in mice: the host and the protozoa perspectives.
Front Cell Infect Microbiol
December 2024
Institut Pasteur de la Guadeloupe, Les Abymes, Guadeloupe, France.
The free-living amoeba (NF) causes a rare but lethal parasitic meningoencephalitis (PAM) in humans. Currently, this disease lacks effective treatments and the specific molecular mechanisms that govern NF pathogenesis and host brain response remain unknown. To address some of these issues, we sought to explore naturally existing virulence diversity within environmental NF isolates.
View Article and Find Full Text PDFArticle Synopsis
- The obligate intracellular parasite replicates within a compartment called the parasitophorous vacuole (PV) and utilizes a protein ingestion pathway to take in nutrients from the host cell's cytosol, initiated by the protein GRA14.
- A genome-wide CRISPR screen revealed that mutants lacking components of this ingestion pathway (GRA14, CPL, or CRT) are forced to rely more on alternative metabolic pathways to survive, such as pyrimidine and fatty acid biosynthesis.
- Analysis showed that these ingestion-deficient mutants had lower levels of key nutrients and growth defects when amino acids were scarce, indicating that the ingestion pathway plays a crucial role in nutrient acquisition during resource-limited conditions.
Profiling Pro-Inflammatory Proteases as Biomolecular Signatures of Material-Induced Subcutaneous Host Response in Immuno-Competent Mice.
Adv Sci (Weinh)
December 2024
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637459, Singapore.
Article Synopsis
- - Proteases play a crucial role in inflammation but are not well-studied in the immune response to biomedical implants, which is essential for their clinical success.
- - The study analyzes the activity of neutrophil elastase, matrix metalloproteinases, and cysteine cathepsins in mice, showing that different materials affect protease activity levels, with biodegradable ones like poly(lactic-co-glycolic) acid triggering the most activity.
- - Results indicate a connection between protease activity and the expression of inflammatory cytokines, suggesting that monitoring protease activity could be a valuable method for assessing the inflammatory response to biomaterials and guiding the development of better implants.
Transcriptome analysis of infected human macrophages between strains of Brucella melitensis and an omp31 mutant.
Cell Mol Biol (Noisy-le-grand)
November 2024
Laboratorio de Microbiología Molecular, Departamento de Microbiología e Inmunología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Autónoma de México, UNAM CU, Coyoacán C.P. 04510, CdMx, México.
Article Synopsis
- Brucella spp. are Gram-negative bacteria that infect humans through animals and can survive within macrophages, but how this interaction works is not well understood.
- The study aimed to explore the responses of human macrophages to different strains of B. melitensis by analyzing gene expression differences following infection.
- Results showed that different strains elicited varied immune responses, with one strain promoting anti-inflammatory responses, while a mutant strain triggered apoptosis and hindered immune evasion, shedding light on brucellosis pathogenesis.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!