Nature Reviews Drug Discovery, Journal Year: 2025, Volume and Issue: unknown
Published: March 18, 2025
Language: Английский
Annual Review of Virology, Journal Year: 2023, Volume and Issue: 10(1), P. 139 - 161
Published: Sept. 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.
Language: Английский
Citations
37
Antiviral Research, Journal Year: 2024, Volume and Issue: 224, P. 105842 - 105842
Published: Feb. 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.
Language: Английский
Citations
9
Microbiology Spectrum, Journal Year: 2022, Volume and Issue: 10(5)
Published: Oct. 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.
Language: Английский
Citations
36
iScience, Journal Year: 2022, Volume and Issue: 25(4), P. 104112 - 104112
Published: March 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.
Language: Английский
Citations
30
Trends in Biochemical Sciences, Journal Year: 2023, Volume and Issue: 48(5), P. 420 - 427
Published: Jan. 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.
Language: Английский
Citations
20
Antiviral Research, Journal Year: 2024, Volume and Issue: 225, P. 105869 - 105869
Published: March 26, 2024
SARS-CoV-2 Omicron subvariants with increased transmissibility and immune evasion are spreading globally alarming persistence. Whether the mutations evolution of spike (S) alter viral hijacking human TMPRSS2 for entry remains to be elucidated. This is particularly important investigate because large number diversity S reported since emergence BA.1. Here we report that a molecular determinant all clinical isolates tested in lung cells, including ancestral (BA.1, BA.2, BA.5), contemporary (BQ.1.1, XBB.1.5, EG.5.1) currently circulating BA.2.86. First, used co-transfection assay demonstrate endoproteolytic cleavage by subvariants. Second, found N-0385, highly potent inhibitor, robust inhibitor virus-like particles harbouring protein Third, show N-0385 exhibits nanomolar broad-spectrum antiviral activity against live Calu-3 cells primary patient-derived bronchial epithelial cells. Interestingly, 10-20 times more than repositioned camostat, BA.5, EG.5.1, We further shows broad synergistic clinically approved direct-acting antivirals (DAAs), i.e., remdesivir nirmatrelvir, subvariants, demonstrating potential therapeutic benefits multi-targeted treatment based on DAAs.
Language: Английский
Citations
6
Expert Opinion on Drug Discovery, Journal Year: 2022, Volume and Issue: 17(5), P. 423 - 425
Published: March 8, 2022
Language: Английский
Citations
27
iScience, Journal Year: 2023, Volume and Issue: 26(2), P. 105944 - 105944
Published: Jan. 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.
Language: Английский
Citations
16
Viruses, Journal Year: 2023, Volume and Issue: 15(7), P. 1577 - 1577
Published: July 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.
Language: Английский
Citations
15
International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 633 - 633
Published: Jan. 13, 2025
The COVID-19 pandemic has caused over 7 million deaths globally in the past four years. Siparuna spp. (Siparunaceae), which is used Brazilian folk medicine, considered a genus with potential antiviral alternatives. This study explored correlation between phytochemicals leaf extracts (S. ficoides, S. decipiens, glycycarpa, reginae, and cymosa) their against various SARS-CoV-2 targets. In vitro assays examined interactions spike protein ACE2 receptor, protease activity, viral replication inhibition Calu-3 cell models. UHPLC-MS/MS analysis, processed MZmine evaluated chemometrically, revealed isoquinoline alkaloids bulbocapnine, showing promising therapeutic potential. Predictions regarding absorption, distribution, metabolism, excretion, toxicity were conducted, along molecular docking dynamics simulations, to evaluate protein−ligand interaction stability. results confirmed activity of targets, 92% maintaining 70% cellular viability at 200 μg·mL−1 80% achieving more than 50% suppression 50 μg·mL−1. These findings highlight as novel anti-coronavirus agents support need for further exploration, isolation, testing compounds fight COVID-19.
Language: Английский
Citations
0