The role of interleukin-6 and janus kinases in the pathogenesis, and treatment of SARS-CoV-2 DOI Open Access
Nightingale Syabbalo

Journal of Lung Pulmonary & Respiratory Research, Journal Year: 2022, Volume and Issue: 9(1), P. 17 - 32

Published: Jan. 1, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a deadly pneumonia caused by an enveloped, single-stranded RNA betacoronavirus belonging to the coronaviridae family. Pathophysiologically, SARS-CoV-2 due severe hyperinflammatory host response coronavirus, resulting in overproduction of cytokines, chemokines, and growth factors macrophages, such as interleukin-1β (IL-1β), IL-2, IL-6, IL-8, IL-10, tumour necrosis factor-α. characterized diffuse alveolar damage direct infection type II pneumocytes, pulmonary edema, vascular occlusion, interstitial infiltrates, ventilation/perfusion mismatch, which rapidly progress hypoxemia, distress syndrome, multi-organ failure, death. The standard care Covid-19, includes high-flow nasal oxygen (HFNO), dexamethasone, remdesivir, mechanical ventilation or extracorporeal membrane oxygenation very cases. However, mortality exceptionally high even with these therapies. Covid-19 dysregulation, over-production including IL-1β, TNF-α. IL-6 plays key role orchestrating hyperinflammation cytokine storm, leads lung injury, failure. Interleukin-6 signaling via transmembrane receptor-α (mIL-6Rα), soluble IL-6Rα. Tocilizumab, sarilumab are IL-6Rα antagonists, have been issued emergency use authorization (EUA) FDA. Both biologics safe, effective treatment particularly patients requiring HFNO, support. Another therapeutic approach treat target downstream JAK/STAT pathway critical inciting immunopathological effects. Baricitimab tofacitinib granted EUA A systemic review has shown that JAK-inhibitors significantly decrease odd (P ˂ 0.0005), ICU admission 0.0005). Additionally JAKinibs increase odds for patient discharge within weeks P 0.00001). Tofacitinib reported lead lower risk failure death through day 28 than placebo hospitalized Covid-19. Barictinib addition care, dexamethasone was associated reduced adults Selective JAK inhibitors usual

Language: Английский

An updated overview of recent advances, challenges, and clinical considerations of IL-6 signaling blockade in severe coronavirus disease 2019 (COVID-19) DOI
Reza Elahi,

Parsa Karami,

Amir Hossein Heidary

et al.

International Immunopharmacology, Journal Year: 2022, Volume and Issue: 105, P. 108536 - 108536

Published: Jan. 11, 2022

Language: Английский

Citations

44
Artificial intelligence for drug repurposing against infectious diseases DOI Creative Commons
Anuradha Singh

Artificial Intelligence Chemistry, Journal Year: 2024, Volume and Issue: 2(2), P. 100071 - 100071

Published: June 12, 2024

Traditional drug discovery struggles to keep pace with the ever-evolving threat of infectious diseases. New viruses and antibiotic-resistant bacteria, all demand rapid solutions. Artificial Intelligence (AI) offers a promising path forward through accelerated repurposing. AI allows researchers analyze massive datasets, revealing hidden connections between existing drugs, disease targets, potential treatments. This approach boasts several advantages. First, repurposing drugs leverages established safety data reduces development time costs. Second, can broaden search for effective therapies by identifying unexpected new targets. Finally, help mitigate limitations predicting minimizing side effects, optimizing repurposing, navigating intellectual property hurdles. The article explores specific strategies like virtual screening, target identification, structure base design natural language processing. Real-world examples highlight AI-driven in discovering treatments

Language: Английский

Citations

9
Antibacterial Potential of Trihydroxycyclohexa-2,4-Diene-1-Carboxylic Acid: Insight from DFT, Molecular Docking, and Molecular Dynamic Simulation DOI

Aniekan E. Owen,

Chioma M. Chima,

Iqrar Ahmad

et al.

Polycyclic aromatic compounds, Journal Year: 2023, Volume and Issue: unknown, P. 1 - 24

Published: May 22, 2023

In this study, (z)-5-((3-(2,3-dihydroxyphenyl) acryloyl) oxy)- 1,3,4-trihydroxycyclohexa-2,4-diene-1-carboxylic acid (chlorogenic acid) was isolated and characterized using UV-Visible, 1H NMR 13C NMR, FT-IR, along with detailed investigation density functional theory (DFT), in-silico molecular docking, dynamics (MD) simulation. Results from DFT calculation indicates that the titled compound is very stable energy gap of 3.7–7.8 for variable functionals, similarly, structural parameters show close agreement X-ray data bond lengths angles. The FT-IR spectrum results revealed stretching vibration O–H (3366 cm−1), C=O (1689 C–H (1636, 1606, 1522, 1442 C–O (1192 1122 cm−1). drug-likeness analyses ADME studies showed ability good oral behavior investigated as it obeys Lipinski, Ghose, Veber Egan rules. Hepatotoxic immunotoxic activities were indicated toxicity/toxicological endpoints studied compound. docking a binding affinity −8.30 9.5 kcal/mol compound, which higher than standard drug. From dynamic simulation results, chlorogenic-2H14 (complex B) variations in RMSD values less 3Å, indicating protein structure underwent minor conformational changes throughout Chlorogenic-protein complexes had average RGyr 3.704 − 4.907Å, compaction during Therefore, can be said has potential to effective an agent cholera management, obtained platform further in-vitro, vivo clinical trials.

Language: Английский

Citations

14
Molecules for COVID-19 treatment DOI
Zhigang Zeng,

Changzhou Liao,

Lei Yu

et al.

Chinese Chemical Letters, Journal Year: 2023, Volume and Issue: 35(7), P. 109349 - 109349

Published: Dec. 2, 2023

Language: Английский

Citations

14
Baricitinib and tofacitinib off‐target profile, with a focus on Alzheimer's disease DOI Creative Commons
Maria Luisa Faquetti, Laura Slappendel, Hélène Bigonne

et al.

Alzheimer s & Dementia Translational Research & Clinical Interventions, Journal Year: 2024, Volume and Issue: 10(1)

Published: Jan. 1, 2024

Abstract INTRODUCTION Janus kinase (JAK) inhibitors were recently identified as promising drug candidates for repurposing in Alzheimer's disease (AD) due to their capacity suppress inflammation via modulation of JAK/STAT signaling pathways. Besides interaction with primary therapeutic targets, JAK inhibitor drugs frequently interact unintended, often unknown, biological off‐targets, leading associated effects. Nevertheless, the relevance inhibitors’ off‐target interactions context AD remains unclear. METHODS Putative off‐targets baricitinib and tofacitinib predicted using a machine learning (ML) approach. After screening scientific literature, filtered based on AD. Targets that had not been previously or subsequently tested biochemical cell‐based assays. From those, active concentrations compared bioavailable brain by physiologically pharmacokinetic (PBPK) modeling. RESULTS With aid ML vitro activity assays, we two enzymes unknown be inhibited baricitinib, namely casein 2 subunit alpha (CK2‐α2) dual leucine zipper (MAP3K12), both binding constant ( K d ) values 5.8 μM. Predicted maximum tissue PBPK modeling range from 1.3 23 nM, which is three orders magnitude below corresponding constant. CONCLUSION In this study, extended list are potentially relevant progression distribution brain. The results suggest low likelihood successful permeability, even at recommended daily dose. While additional research needed evaluate potential impact AD, combined approach ML‐based target prediction, confirmation, may help prioritize high being effectively repurposed Highlights This study explored inhibitors' multidisciplinary We learning, tests, modelling predict validate new Previously inhibition (CK2‐a2 MAP3K12) confirmed experiments. Our model indicates permeability limits repurposing. proposed optimizes efforts research.

Language: Английский

Citations

5
Water resource rejuvenation via AOP based degradation of pharmaceuticals extensively used during COVID-19 DOI

Vineeta Singh,

Shashi Prakash Gupta,

Sujoy Kumar Samanta

et al.

Journal of Water Process Engineering, Journal Year: 2024, Volume and Issue: 67, P. 106137 - 106137

Published: Sept. 14, 2024

Language: Английский

Citations

5
Integrating clinical pharmacology and artificial intelligence: potential benefits, challenges, and role of clinical pharmacologists DOI
Harmanjit Singh, Dwividendra Kumar Nim,

Aaronbir Singh Randhawa

et al.

Expert Review of Clinical Pharmacology, Journal Year: 2024, Volume and Issue: 17(4), P. 381 - 391

Published: Feb. 10, 2024

The integration of artificial intelligence (AI) into clinical pharmacology could be a potential approach for accelerating drug discovery and development, improving patient care, streamlining medical research processes.

Language: Английский

Citations

4
Structure–Activity Relationship of Ciprofloxacin towards S-Spike Protein of SARS-CoV-2: Synthesis and In-Silico Evaluation DOI
Sahil Kumar,

Papiya Dey,

Arup Kumar Pathak

et al.

Journal of Chemical Information and Modeling, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 12, 2025

The recent outbreak of the coronavirus (COVID-19) pandemic, caused by SARS-CoV-2 virus, has posed serious threats to global health systems. Although several directions have been put WHO for effective treatment, use antibiotics, particularly ciprofloxacin, in suspected and acquired Covid-19 patients raised an even more concern antibiotic resistance. Ciprofloxacin reported inhibit entry into host cells via interacting with spike (S) protein. However, a proper structure-activity relationship study ciprofloxacin S-protein is lacking, which inhibits researchers from developing potent fluoroquinolone analogue, specific inhibition viral entry. Herein, order study, we accomplished short convergent synthesis different derivatives detailed

Language: Английский

Citations

0
The future of pharmaceuticals: Artificial intelligence in drug discovery and development DOI Creative Commons
Chen Fu, Qi Chen

Journal of Pharmaceutical Analysis, Journal Year: 2025, Volume and Issue: unknown, P. 101248 - 101248

Published: Feb. 1, 2025

Language: Английский

Citations

0
Cutting-edge AI tools revolutionizing scientific research in life sciences DOI Creative Commons

Katarzyna Lorenc-Kukula

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

Published: March 7, 2025

Artificial intelligence (AI) is becoming a transformative force in the life sciences, pushing boundaries of possibility. Imagine AI automating time-consuming tasks, uncovering hidden patterns vast datasets, designing proteins minutes instead years, and even predicting disease outbreaks before they occur. This review explores latest tools revolutionizing scientific fields, including research data analysis, healthcare, supporting writing. Beyond processing, reshaping how scientists draft share their findings, enhancing processes ranging from literature reviews to citation management. However, with great power comes responsibility. Are we prepared for this leap? delves into forefront where innovation meets

Language: Английский

Citations

0