Viral Membrane Fusion: A Dance Between Proteins and Lipids

Annual Review of Virology, Год журнала: 2023, Номер 10(1), С. 139 - 161

Опубликована: Сен. 29, 2023

There are at least 21 families of enveloped viruses that infect mammals, and many contain members high concern for global human health. All have a dedicated fusion protein or complex enacts the critical genome-releasing membrane event is essential before viral replication within host cell interior can begin. Because all enter cells by fusion, it behooves us to know how proteins function. Viral also major targets neutralizing antibodies, hence they serve as key vaccine immunogens. Here we review current concepts about focusing on triggered, structural intermediates between pre- postfusion forms, their interplay with lipid bilayers engage. We discuss cellular therapeutic interventions thwart virus-cell fusion.

Язык: Английский

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Antiviral strategies against influenza virus: an update on approved and innovative therapeutic approaches

Cellular and Molecular Life Sciences, Год журнала: 2025, Номер 82(1)

Опубликована: Фев. 13, 2025

Язык: Английский

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Computational drug repurposing: approaches, evaluation of in silico resources and case studies

Nature Reviews Drug Discovery, Год журнала: 2025, Номер unknown

Опубликована: Март 18, 2025

Язык: Английский

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Combinations of Host- and Virus-Targeting Antiviral Drugs Confer Synergistic Suppression of SARS-CoV-2

Microbiology Spectrum, Год журнала: 2022, Номер 10(5)

Опубликована: Окт. 3, 2022

Imagine a future viral pandemic where if you test positive for the new virus, can quickly take some medicines at home few days so that do not get too sick. To date, only single drugs have been approved outpatient use against SARS-CoV-2, and we are learning these limitations may succumb to drug resistance.

Язык: Английский

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Mono- and combinational drug therapies for global viral pandemic preparedness

iScience, Год журнала: 2022, Номер 25(4), С. 104112 - 104112

Опубликована: Март 17, 2022

Broadly effective antiviral therapies must be developed to ready for clinical trials, which should begin soon after the emergence of new life-threatening viruses. Here, we pave way towards this goal by reviewing conserved druggable virus-host interactions, mechanisms action, immunomodulatory properties available broad-spectrum antivirals (BSAs), routes BSA delivery, and interactions BSAs with other antivirals. Based on review, concluded that range indications can expanded, pan- cross-viral mono- combinational developed. We have also a scoring algorithm help identify most promising few thousands potential BSA-containing drug cocktails (BCCs) prioritize their development during critical period between identification virus virus-specific vaccines, drugs, therapeutic antibodies.

Язык: Английский

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SLiM-binding pockets: an attractive target for broad-spectrum antivirals

Trends in Biochemical Sciences, Год журнала: 2023, Номер 48(5), С. 420 - 427

Опубликована: Янв. 7, 2023

Short linear motif (SLiM)-mediated interactions offer a unique strategy for viral intervention due to their compact interfaces, ease of convergent evolution, and key functional roles. Consequently, many viruses extensively mimic host SLiMs hijack or deregulate cellular pathways the same motif-binding pocket is often targeted by numerous unrelated viruses. A toolkit therapeutics targeting commonly mimicked could provide prophylactic therapeutic broad-spectrum antivirals vastly improve our ability treat ongoing future outbreaks. In this opinion article, we discuss relevance SLiMs, advocating suitability as targets antiviral inhibitors.

Язык: Английский

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The combination of pleconaril, rupintrivir, and remdesivir efficiently inhibits enterovirus infections in vitro, delaying the development of drug-resistant virus variants

Antiviral Research, Год журнала: 2024, Номер 224, С. 105842 - 105842

Опубликована: Фев. 26, 2024

Enteroviruses are a significant global health concern, causing spectrum of diseases from the common cold to more severe conditions like hand-foot-and-mouth disease, meningitis, myocarditis, pancreatitis, and poliomyelitis. Current treatment options for these infections limited, underscoring urgent need effective therapeutic strategies. To find better option we analyzed efficacy 12 known broad-spectrum anti-enterovirals both individually in combinations against different enteroviruses vitro. We identified several novel, synergistic two-drug three-drug that demonstrated inhibition enterovirus Specifically, triple-drug combination pleconaril, rupintrivir, remdesivir exhibited remarkable echovirus (EV) 1, EV6, EV11, coxsackievirus (CV) B5, human lung epithelial A549 cells. This surpassed effectiveness single-agent or dual-drug treatments, as evidenced by its ability protect cells EV1-induced cytotoxicity across seven passages. Additionally, this cocktail showed potent antiviral activity EV-A71 intestinal organoids. Thus, our findings highlight potential pleconaril-rupintrivir-remdesivir range infections. The study also paves way towards development strategic drug with virus family coverage high-resistance barriers.

Язык: Английский

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What are the current challenges for machine learning in drug discovery and repurposing?

Expert Opinion on Drug Discovery, Год журнала: 2022, Номер 17(5), С. 423 - 425

Опубликована: Март 8, 2022

Язык: Английский

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Identification of novel antiviral drug candidates using an optimized SARS-CoV-2 phenotypic screening platform

iScience, Год журнала: 2023, Номер 26(2), С. 105944 - 105944

Опубликована: Янв. 7, 2023

Reliable, easy-to-handle phenotypic screening platforms are needed for the identification of anti-SARS-CoV-2 compounds. Here, we present caspase 3/7 activity as a readout monitoring replication SARS-CoV-2 isolates from different variants, including remdesivir-resistant strain, and other coronaviruses in numerous cell culture models, independently cytopathogenic effect formation. Compared to Caco-2 subline Caco-2-F03 displayed superior performance. It possesses stable susceptibility phenotype does not produce false-positive hits due drug-induced phospholipidosis. A proof-of-concept screen 1,796 kinase inhibitors identified known novel antiviral drug candidates phosphoglycerate dehydrogenase (PHGDH), CDC like 1 (CLK-1), colony stimulating factor receptor (CSF1R). The PHGDH inhibitor NCT-503 was further increased combination with hexokinase II (HK2) 2-deoxy-D-glucose, which is clinical development COVID-19. In conclusion, detection SARS-CoV-2-infected cells provides simple high-throughput platform that reduces hits.

Язык: Английский

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Synergistic Activity of Remdesivir–Nirmatrelvir Combination on a SARS-CoV-2 In Vitro Model and a Case Report

Viruses, Год журнала: 2023, Номер 15(7), С. 1577 - 1577

Опубликована: Июль 19, 2023

Background: This study aims to investigate the activity of remdesivir–nirmatrelvir combination against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and report a case Coronavirus Disease 2019 (COVID-19) cured with this combination. Methods: A Vero E6 cell-based infection assay was used in vitro The SARS-CoV-2 strains tested were 20A.EU1, BA.1 BA.5. After incubation, viability performed. supernatants collected for viral titration. Highest Single Agent (HSA) reference model calculated. An HSA score >10 is considered synergic. Results: Remdesivir nirmatrelvir showed synergistic at 48 72 h, an 52.8 28.6, respectively (p < 0.0001). These data confirmed by performing supernatant titration omicron variants: reduced titer better than more active compound alone. immunocompromised patient prolonged critical COVID-19 successfully treated remdesivir, nirmatrelvir/ritonavir, tixagevimab/cilgavimab dexamethasone, excellent clinical–radiological response. However, she required further off-label therapy nirmatrelvir/ritonavir until negative. Conclusions: Remdesivir–nirmatrelvir has synergic vitro. may have role immunosuppressed patients severe shedding.

Язык: Английский

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