Identification of oral therapeutics using an AI platform against the virus responsible for COVID-19, SARS-CoV-2 DOI Creative Commons

Adam Bess,

Frej Berglind,

Supratik Mukhopadhyay

и другие.

Frontiers in Pharmacology, Год журнала: 2023, Номер 14

Опубликована: Дек. 22, 2023

Purpose: This study introduces a sophisticated computational pipeline, eVir , designed for the discovery of antiviral drugs based on their interactions within human protein network. There is pressing need cost-effective therapeutics infectious diseases (e.g., COVID-19), particularly in resource-limited countries. Therefore, our team devised an Artificial Intelligence (AI) system to explore repurposing opportunities currently used oral therapies. The operates by identifying pharmaceutical compounds that mirror effects peptides (AVPs)—fragments proteins known interfere with fundamental phases viral life cycle: entry, fusion, and replication. extrapolates probable efficacy given compound analyzing its established predicted impacts protein-protein interaction innovative approach provides promising platform drug against SARS-CoV-2 or any virus which peptide data available. Methods: AI software pipeline processes drug-protein networks generated from open-source datasets. uses Node2Vec, graph embedding technique, understand nuanced connections among proteins. embeddings are input Siamese Network (SNet) MLPs, each tailored specific mechanisms replication, evaluate similarity between AVPs. Scores SNet MLPs undergo Platt probability calibration combined into unified score gauges potential drug. integrated seeks boost identification confidence, offering solution detecting therapeutic candidates pronounced potency. Once identified number were tested toxicity lung carcinoma cells (Calu-3) infected SARS-CoV-2. A lead was further determine K18-hACE2 mice Computational Predictions: confidently differentiated similar dissimilar pairs accuracy 97.28% AUC 99.47%. Key through these included Zinc, Mebendazole, Levomenol, Gefitinib, Niclosamide, Imatinib. Notably, Mebendazole Zinc showcased highest scores, while Imatinib, Levemenol, Gefitinib also ranked top 20, suggesting significant pharmacological potentials. Further examination binding analysis using explainable focused reverse engineering causality networks. Protein scores Imatinib revealed notable such as CDPK1, VEGF2, ABL1, several tyrosine kinases. Laboratory Studies: determined Topotecan some extent Carfilzomib showed conventional drug-response curves, IC50 values near below Remdesivir excellent confidence all above R2>0.91, no cytotoxicity at concentration Calu-3 cells. Cyclosporine activity, but unconventional curves low R2 explained non-dose dependent compound. Additionally, Niclosamide demonstrated curve high confidence; however, inherent may be confounding element misrepresents true efficacy, reflecting cellular damage rather than genuine action. control evaluated parallel submitted test article had validating overall results assay. cell studies have non-toxic concentrations administered SARS-CoV-2, resulted 44.2% reduction load compared non-treated placebo respectively. differences body weight clinical chemistry determinations (i.e., kidney liver enzymes) different treatment groups. Conclusion: research underscores existing treating COVID-19. Our preliminary findings underscore promise compounds, notably both vitro vivo settings Several explored, especially off-label medication; cost-effectiveness position them economical therapies

Язык: Английский

Natural-product-based, carrier-free, noncovalent nanoparticles for tumor chemo-photodynamic combination therapy DOI Creative Commons
Zhonglei Wang, Liyan Yang

Pharmacological Research, Год журнала: 2024, Номер 203, С. 107150 - 107150

Опубликована: Март 21, 2024

Cancer, with its diversity, heterogeneity, and complexity, is a significant contributor to global morbidity, disability, mortality, highlighting the necessity for transformative treatment approaches. Photodynamic therapy (PDT) has aroused continuous interest as viable alternative conventional cancer treatments that encounter drug resistance. Nanotechnology brought new advances in medicine shown great potential delivery treatment. For precise efficient therapeutic utilization of such tumor approach high spatiotemporal selectivity minimal invasiveness, carrier-free noncovalent nanoparticles (NPs) based on chemo-photodynamic combination essential. Utilizing natural products foundation nanodrug development offers unparalleled advantages, including exceptional pharmacological activity, easy functionalization/modification, well biocompatibility. The natural-product-based, carrier-free, NPs revealed excellent synergistic anticancer activity comparison free photosensitizers bioactive products, representing an favorable avenue improve efficacy. Herein, comprehensive summary current strategies representative application examples past decade (such paclitaxel, 10-hydroxycamptothecin, doxorubicin, etoposide, combretastatin A4, epigallocatechin gallate, curcumin) therapy. We highlight insightful design synthesis smart aim enhance PDT Meanwhile, we discuss future challenges opportunities associated these provide enlightenment, spur innovative ideas, facilitate PDT-mediated clinical transformation.

Язык: Английский

Процитировано

15
Crosstalk between ROS-inflammatory gene expression axis in the progression of lung disorders DOI
Sumel Ashique, Neeraj Mishra, Shubhrajit Mantry

и другие.

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2024, Номер unknown

Опубликована: Авг. 28, 2024

Язык: Английский

Процитировано

7
Substitutions in SARS-CoV-2 Mpro Selected by Protease Inhibitor Boceprevir Confer Resistance to Nirmatrelvir DOI Creative Commons
Karen Anbro Gammeltoft, Yuyong Zhou, Line A. Ryberg

и другие.

Viruses, Год журнала: 2023, Номер 15(9), С. 1970 - 1970

Опубликована: Сен. 21, 2023

Nirmatrelvir, which targets the SARS-CoV-2 main protease (Mpro), is first-in-line drug for prevention and treatment of severe COVID-19, additional Mpro inhibitors are in development. However, risk resistance development threatens future efficacy such direct-acting antivirals. To gain knowledge on viral correlates to inhibitors, we selected resistant under with nirmatrelvir-related inhibitor boceprevir. during five escape experiments VeroE6 cells showed cross-resistance nirmatrelvir up 7.3-fold increased half-maximal effective concentration compared original SARS-CoV-2, determined concentration–response experiments. Sequence analysis revealed that viruses harbored substitutions L50F A173V. For reverse genetic studies, these were introduced into a cell-culture-infectious clone. Infectivity titration stability cell-culture-derived engineered mutants rescued fitness cost conferred by In experiments, A173V was driver boceprevir nirmatrelvir. Structural suggested can cause making binding less favorable. This study contributes comprehensive overview profile COVID-19 thus inform population monitoring contribute pandemic preparedness.

Язык: Английский

Процитировано

13
Herbal Medicines as Complementary Therapy for Managing Complications in COVID-19 Patients with Diabetes Mellitus DOI Creative Commons

Syah Akbarul Adha,

Nadiya Nurul Afifah,

Irma Rahayu Latarissa

и другие.

Diabetes Metabolic Syndrome and Obesity, Год журнала: 2025, Номер Volume 18, С. 135 - 146

Опубликована: Янв. 1, 2025

Diabetes mellitus (DM) is recognized and classified as a group of conditions marked by persistent high blood glucose levels. It also an inflammatory condition that may influence concurrent disease states, including Coronavirus Disease 2019 (COVID-19). Currently, no effective drug has been found to treat COVID-19, especially in DM patients. Many herbal medicines, such the well-known Andrographis paniculata, have explored drugs complementary therapies due their antidiabetic, antibacterial, antiviral, anti-inflammatory, immunomodulatory effects. This study aimed examine potential medicines therapy patients with COVID-19 complications, drawing from in-vitro in-vivo investigations. analyzed articles published within last 15 years using keywords "herbal medicines", "COVID-19", "Diabetes Mellitus", "antidiabetics", "antiviral", "anti-inflammatory". The results showed several could serve for complications. These include Ageratum conyzoides, Artocarpus altilis, Centella asiatica, Momordica charantia, Persea gratissima, Phyllanthus urinaria, Physalis angulata, Tinospora cordifolia, Zingiber zerumbet. Herbal but these claims need experimental validation infection models among affected

Язык: Английский

Процитировано

0
Self-managing symptoms of Long COVID: an education and strategies research protocol DOI Creative Commons
Julia Rybkina, Nithin Jacob,

Brenda Colella

и другие.

Frontiers in Public Health, Год журнала: 2024, Номер 12

Опубликована: Фев. 7, 2024

Post-acute sequelae of SARS-COV-2 (PASC) is growing in prevalence, and involves symptoms originating from the central neurological, cardiovascular, respiratory, gastrointestinal, autonomic nervous, or immune systems. There are non-specific such as fatigue, headaches, brain fog, which cannot be ascribed to a single system. PASC places notable strain on our healthcare system, already laden with large number acute-COVID-19 patients. Furthermore, it impedes social, academic vocational functioning, impacts family life, relationships, work/financial life. The treatment for needs target this etiology wide-ranging sequelae. In conditions similar PASC, “chemo brain,” prolonged concussion, have shown effectively managed through education strategies self-management Mindfulness interventions. However, interventions yet empirically evaluated knowledge. response gap, we developed virtual intervention synthesized by psychiatrists clinical psychologists current study. We will undertake two-phase randomized controlled trial determine feasibility (Phase 1; N = 90) efficacy 2; sample sized based phase 1 results) novel 8 week Education Self-Management Strategies group compared mindfulness skills program, both delivered virtually. Main outcomes include confidence/ability self-manage symptoms, quality utilization. This study stands mitigate deleterious intrusiveness everyday life patients may also help reduce impact Clinical registration: https://classic.clinicaltrials.gov/ct2/show/NCT05268523 ; identifier NCT05268523.

Язык: Английский

Процитировано

3
Oral Bioavailability, Tissue Distribution, Metabolism, and Excretion of Panduratin A from Boesenbergia rotunda Extract in Healthy Rats DOI Creative Commons

Teetat Kongratanapasert,

Tussapon Boonyarattanasoonthorn, Kittitach Supannapan

и другие.

Drug Design Development and Therapy, Год журнала: 2024, Номер Volume 18, С. 2905 - 2917

Опубликована: Июль 1, 2024

Our previous studies in vitro and vivo have shown anti-severe acute respiratory syndrome coronavirus 2 activity of fingerroot extract (

Язык: Английский

Процитировано

3
Cytokine Storm in COVID-19: Insight into Pathological Mechanisms and Therapeutic Benefits of Chinese Herbal Medicines DOI Creative Commons
Qingyuan Yu, Xian Zhou,

Rotina Kapini

и другие.

Medicines, Год журнала: 2024, Номер 11(7), С. 14 - 14

Опубликована: Июль 18, 2024

Cytokine storm (CS) is the main driver of SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) in severe coronavirus disease-19 (COVID-19). The pathological mechanisms CS are quite complex and involve multiple critical molecular targets that turn self-limited mild COVID-19 into a life-threatening concern. At present, vaccines strongly recommended as safe effective treatments for preventing serious illness or death from COVID-19. However, treatment options still lacking people who at most risk hospitalized with disease. Chinese herbal medicines have been shown to improve clinical outcomes an adjunct therapy, particular development ARDS. This review illustrates detail pathogenesis CS-involved ARDS its associated key targets, cytokines signalling pathways. therapeutic were identified particularly relation turning points COVID-19, symptoms Preclinical studies reviewed effects together conventional therapies reducing addressing CS. Multiple formulations, extracts single bioactive phytochemicals without demonstrated strong anti-CS through mechanisms. evidence larger, well-designed trials their detailed action yet be well elucidated. More research warranted further evaluate value medicine COVID-19-induced

Язык: Английский

Процитировано

3
SARS-CoV-2 replication and drug discovery DOI Creative Commons

Farah Nazir,

Arnaud John Kombe Kombe,

Zunera Khalid

и другие.

Molecular and Cellular Probes, Год журнала: 2024, Номер 77, С. 101973 - 101973

Опубликована: Июль 24, 2024

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome 2 (SARS-CoV-2) has killed millions of people and continues to wreak havoc across globe. This sudden deadly pandemic emphasizes necessity for anti-viral drug development that can be rapidly administered reduce morbidity, mortality, virus propagation. Thus, lacking efficient anti-COVID-19 treatment, especially given lengthy process as well critical death tool been associated with SARS-CoV-2 since its outbreak, repurposing (or repositioning) constitutes so far, ideal ready-to-go best approach in mitigating viral spread, containing infection, reducing COVID-19-associated rate. Indeed, based on molecular similarity previous coronaviruses (CoVs), repurposed drugs have reported hamper replication. Therefore, understanding inhibition mechanisms replication chemicals known block CoV multiplication is crucial, it opens way particular treatment options COVID-19 therapeutics. In this review, we highlighted basics underlying drug-repurposing strategies against SARS-CoV-2. Notably, discussed replication, involving including proteases (3C-like protease, 3CL

Язык: Английский

Процитировано

3
Stand Up to Stand Out: Natural Dietary Polyphenols Curcumin, Resveratrol, and Gossypol as Potential Therapeutic Candidates against Severe Acute Respiratory Syndrome Coronavirus 2 Infection DOI Open Access
Zhonglei Wang, Xian-qing Song,

Wenjing Xu

и другие.

Nutrients, Год журнала: 2023, Номер 15(18), С. 3885 - 3885

Опубликована: Сен. 6, 2023

The COVID-19 pandemic has stimulated collaborative drug discovery efforts in academia and the industry with aim of developing therapies vaccines that target SARS-CoV-2. Several novel have been approved deployed last three years. However, their clinical application revealed limitations due to rapid emergence viral variants. Therefore, development next-generation SARS-CoV-2 therapeutic agents a high potency safety profile remains priority for global health. Increasing awareness “back nature” approach improving human health prompted renewed interest natural products, especially dietary polyphenols, as an additional strategy treat patients, owing its good profile, exceptional nutritional value, health-promoting benefits (including potential antiviral properties), affordability, availability. Herein, we describe biological properties pleiotropic molecular mechanisms polyphenols curcumin, resveratrol, gossypol inhibitors against variants observed vitro vivo studies. Based on advantages disadvantages obtain maximal benefits, several strategies such nanotechnology (e.g., curcumin-incorporated nanofibrous membranes antibacterial-antiviral ability), lead optimization methylated analog curcumin), combination specific plant extracts micronutrients), broad-spectrum activities broadly inhibits coronaviruses) also emphasized positive factors facilitation anti-SARS-CoV-2 support effective long-term management control.

Язык: Английский

Процитировано

8
Safety and efficacy of Paxlovid in the treatment of adults with mild to moderate COVID-19 during the omicron epidemic: a multicentre study from China DOI

Pulin Li,

Ling Huang, Rui Han

и другие.

Expert Review of Anti-infective Therapy, Год журнала: 2024, Номер 22(6), С. 469 - 477

Опубликована: Фев. 1, 2024

Background Since December 2022, the Omicron variant has led to a widespread pandemic in China. The study was explore safety and effectiveness of Paxlovid for treatment coronavirus disease 2019 (COVID-19).

Язык: Английский

Процитировано

2