Accurate and interpretable drug-drug interaction prediction enabled by knowledge subgraph learning

Communications Medicine, Journal Year: 2024, Volume and Issue: 4(1)

Published: March 28, 2024

Abstract Background Discovering potential drug-drug interactions (DDIs) is a long-standing challenge in clinical treatments and drug developments. Recently, deep learning techniques have been developed for DDI prediction. However, they generally require huge number of samples, while known DDIs are rare. Methods In this work, we present KnowDDI, graph neural network-based method that addresses the above challenge. KnowDDI enhances representations by adaptively leveraging rich neighborhood information from large biomedical knowledge graphs. Then, it learns subgraph each drug-pair to interpret predicted DDI, where edges associated with connection strength indicating importance or resembling between whose unknown. Thus, lack implicitly compensated enriched propagated similarities. Results Here show evaluation results on two benchmark datasets. obtains state-of-the-art prediction performance better interpretability. We also find suffers less than existing works given sparser graph. This indicates similarities play more important role compensating when enriched. Conclusions nicely combines efficiency prior As an original open-source tool, can help detect possible broad range relevant interaction tasks, such as protein-protein interactions, drug-target disease-gene eventually promoting development biomedicine healthcare.

Language: Английский

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COVID-19 therapeutics

Clinical Microbiology Reviews, Journal Year: 2024, Volume and Issue: 37(2)

Published: May 21, 2024

SUMMARYSince the emergence of COVID-19 in 2020, an unprecedented range therapeutic options has been studied and deployed. Healthcare providers have multiple treatment approaches to choose from, but efficacy those often remains controversial or compromised by viral evolution. Uncertainties still persist regarding best therapies for high-risk patients, drug pipeline is suffering fatigue shortage funding. In this article, we review antiviral activity, mechanism action, pharmacokinetics, safety therapies. Additionally, summarize evidence from randomized controlled trials on various antivirals discuss unmet needs which should be addressed.

Language: Английский

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GabaAergic sedative prospection of sclareol-linalool co-treatment: An antagonistic intervention through in vivo and in silico studies

Neuroscience Letters, Journal Year: 2024, Volume and Issue: unknown, P. 138060 - 138060

Published: Nov. 1, 2024

Language: Английский

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Unpacking the sepsis controversy

Trauma Surgery & Acute Care Open, Journal Year: 2025, Volume and Issue: 10(1), P. e001733 - e001733

Published: March 1, 2025

Despite its many definitions and revisions, consensus statements clinical guidelines, the term 'sepsis' continues to be referred as a discrete entity that is often claimed direct cause of mortality. The assertion sepsis can defined 'life-threatening organ dysfunction caused by dysregulated host response infection,' has led field dominated failed trials informed host-centered, pathogen-agnostic, animal experiments in which models do not recapitulate condition. observations from National Health Service England claim 77.5% deaths occur those aged 75 years or older USA indicating most patients dying have also been diagnosed with 'hospice qualifying conditions,' seem refute by, rather than associated with, 'dysregulated response.' This piece challenges current conceptual framework forms basis definition. Here we posit result both definition use inappropriate models, ineffective treatments continue pursued this field.

Language: Английский

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Caffeine and sclareol take the edge off the sedative effects of linalool, possibly through the GABAA interaction pathway: molecular insights through in vivo and in silico studies

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 11, 2025

Language: Английский

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A small-molecule SARS-CoV-2 inhibitor targeting the membrane protein

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Abstract The membrane (M) protein of betacoronaviruses is well conserved and has a key role in viral assembly 1,2 . Here we describe the identification JNJ-9676, small-molecule inhibitor targeting coronavirus M protein. JNJ-9676 demonstrates vitro nanomolar antiviral activity against SARS-CoV-2, SARS-CoV sarbecovirus strains from bat pangolin zoonotic origin. Using cryogenic electron microscopy (cryo-EM), determined binding pocket formed by transmembrane domains dimer. Compound stabilized dimer an altered conformational state between its long short forms, preventing release infectious virus. In pre-exposure Syrian golden hamster model, (25 mg per kg twice day) showed excellent efficacy, illustrated significant reduction load virus lung 3.5 4 log 10 -transformed RNA copies 50% tissue culture infective dose (TCID 50 ) lung, respectively. Histopathology scores at this were reduced to baseline. post-exposure was efficacious 75 day even when added 48 h after infection, peak loads observed. attractive target block replication, represents interesting chemical series towards identifying clinical candidates addressing current future pandemics.

Language: Английский

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Efficacy and safety of sotrovimab in patients with COVID‐19: A rapid review and meta‐analysis

Reviews in Medical Virology, Journal Year: 2022, Volume and Issue: 32(6)

Published: Oct. 12, 2022

The therapeutic potential of sotrovimab in the treatment coronavirus disease 2019 (COVID-19) is a controversial issue. aim this study was to evaluate efficacy and safety COVID-19 patients. To end, PubMed, Cochrane Library, Embase, Web Science, medRxiv, Google Scholar were searched up 15 August 2022. reference lists key studies also scanned find additional records. Meta-analysis performed using Comprehensive Meta-Analysis. Seventeen involving 27,429 patients included. A significant difference observed mortality rate (odds ratio [OR] = 0.40; 95% CI: 0.25-0.63, p 0.00), hospitalisation (OR 0.53; 0.43-0.65. hospital or death 0.43; 0.25-0.73, need for mechanical ventilation 0.57; 0.33-0.96, 0.03), ICU admission 0.33; 0.17-0.67, 0.00) sotrovimab-receiving group compared those having no sotrovimab. However, between two groups terms progression 0.45; 0.16-1.24, 0.12) emergency department visit 1.01; 0.83-1.24, 0.87). had incidence adverse events 0.98; 0.78-1.23, 0.88). findings present meta-analysis support that could be an effective safe option reduce both Delta Omicron Variants COVID-19.

Language: Английский

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Antiviral combination therapies for persistent COVID-19 in immunocompromised patients

International Journal of Infectious Diseases, Journal Year: 2023, Volume and Issue: 137, P. 55 - 59

Published: Sept. 30, 2023

After the third year of COVID-19 pandemic, most severe burden falls upon immunocompromised patients who cannot mount an endogenous immune response after both vaccination and/or natural infection. They also experience persistent SARS-CoV-2 infection with high viral loads often unsuccessfully managed by standard antiviral monotherapy regimen initially validated for treatment immunocompetent patients, only. The off-label prescription such regimens in is likely to drive emergence treatment-related escape, relapses, excess morbidity, and mortality from delayed underlying disorders. A possible approach mitigate consequence based on combined therapies.

Language: Английский

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UV 254 nm is more efficient than UV 222 nm in inactivating SARS-CoV-2 present in human saliva

Photodiagnosis and Photodynamic Therapy, Journal Year: 2022, Volume and Issue: 39, P. 103015 - 103015

Published: July 14, 2022

Language: Английский

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Pharmacokinetic considerations for enhancing drug repurposing opportunities of anthelmintics: Niclosamide as a case study

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 173, P. 116394 - 116394

Published: March 11, 2024

Recently, anthelmintics have showcased versatile therapeutic potential in addressing various diseases, positioning them as promising candidates for drug repurposing. However, challenges such low bioavailability and a lack of solid pharmacokinetic basis impede successful To overcome these flaws, we aimed to investigate the key factors mainly focusing on absorption, distribution, metabolism profiles by employing niclosamide (NIC) model drug. The intestinal permeability NIC is significantly influenced solubility doesn't function substrate efflux transporters. It showed high plasma protein binding. Also, study indicated that would metabolic stability extensively undergoing glucuronidation. Additionally, investigated CYP-mediated drug-drug interaction both direct time-dependent ways. strong inhibitory effects CYP1A2 CYP2C8 not likely become inhibitor. Our findings could contribute identification essential pharmacokinetics anthelmintics, potentially facilitating their repositioning.

Language: Английский

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