Evaluation of therapeutic potentials of some bioactive compounds in selected African plants targeting main protease (Mpro) in SARS-CoV-2: a molecular docking study DOI Creative Commons
Ishola Abeeb Akinwumi,

Barakat Olamide Ishola,

Oluwatosin M. Adeyemo

et al.

Egyptian Journal of Medical Human Genetics, Journal Year: 2023, Volume and Issue: 24(1)

Published: Dec. 11, 2023

Abstract Background Coronavirus disease 2019 (COVID-19) is an infectious brought on by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a global treat in early 2020. Despite worldwide research proving different medications used to COVID-19, infection still affects human race; we need continue researching virus protect humanity and reduce complications that some might cause. This study focuses finding another promising therapeutic compound against SARS-CoV-2. Twenty-four (24) bioactive compounds were selected from following African plants' Adansonia digitata L, Aframomum melegueta K. Schum, Ageratum conyzoides (L.) L , Boswellia dalzielii, Remdesivir was as control medication. The PubChem web server acquired 3D structures of plant SARS-CoV-2 main protease (M pro ) crystal structure obtained using Protein Data Bank (PDB). Using SwissADME server, compounds' drug-likeness assessed, AutoDock employed for molecular docking with M . Proteins Plus Protein–Ligand Interaction Profiler servers analyse docked complexes. Furthermore, admetSAR website utilized predict ligands' absorption, distribution, metabolism, excretion, toxicity (ADMET) properties. Results Based screening, Rutin violated more than one Lipinski rules five, while two. Molecular analysis results indicated Catechin, Epicatechin, Vitexin, Quercetin, Kaempferol, Gamma-Sitosterol, Kaur-16-ene exhibited stronger binding affinity scores − 7.1, 8.0, 7.3, 7.2, 6.8, 6.5 kcal/mol, respectively, compared Remdesivir's score 6.3 kcal/mol. Consequently, suggest their potential biological activity protease. Additionally, these favourable ADMET Vitexin also has plasma protein below 90%, medication distribution feature. Conclusions shows have better affinities Remdesivir. dynamics simulation vitro vivo investigation required support this study.

Language: Английский

Interaction between host G3BP and viral nucleocapsid protein regulates SARS-CoV-2 replication and pathogenicity DOI Creative Commons
Zemin Yang, Bryan A. Johnson, Victoria Meliopoulos

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(3), P. 113965 - 113965

Published: March 1, 2024

G3BP1/2 are paralogous proteins that promote stress granule formation in response to cellular stresses, including viral infection. The nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inhibits assembly and interacts with via an ITFG motif, residue F17, the N protein. Prior studies examining impact G3PB1-N interaction on SARS-CoV-2 replication have produced inconsistent findings, role this pathogenesis is unknown. Here, we use structural biochemical analyses define residues required for G3BP1-N structure-guided mutagenesis selectively disrupt interaction. We find N-F17A mutation causes highly specific loss G3BP1/2. fails inhibit cells, has decreased replication, pathology vivo. Further mechanistic indicate N-F17-mediated promotes infection by limiting sequestration genomic RNA (gRNA) into granules.

Language: Английский

Citations

25
New perspective of small-molecule antiviral drugs development for RNA viruses DOI
Shasha Li, Huixia Li,

Ruiya Lian

et al.

Virology, Journal Year: 2024, Volume and Issue: 594, P. 110042 - 110042

Published: March 7, 2024

Language: Английский

Citations

8
Network pharmacology and molecular docking: combined computational approaches to explore the antihypertensive potential of Fabaceae species DOI Creative Commons

Zainab Shahzadi,

Zubaida Yousaf, İrfan Anjum

et al.

Bioresources and Bioprocessing, Journal Year: 2024, Volume and Issue: 11(1)

Published: May 20, 2024

Abstract Hypertension is a major global public health issue, affecting quarter of adults worldwide. Numerous synthetic drugs are available for treating hypertension; however, they often come with higher risk side effects and long-term therapy. Modern formulations active phytoconstituents gaining popularity, addressing some these issues. This study aims to discover novel antihypertensive compounds in Cassia fistula , Senna alexandrina occidentalis from family Fabaceae understand their interaction mechanism hypertension targeted genes, using network pharmacology molecular docking. Total 414 were identified; initial screening was conducted based on pharmacokinetic ADMET properties, particular emphasis adherence Lipinski's rules. 6 compounds, namely Germichrysone, Benzeneacetic acid, Flavan-3-ol, 5,7,3',4'-Tetrahydroxy-6, 8-dimethoxyflavon, Dihydrokaempferol, Epiafzelechin, identified as effective agents. Most the found non-toxic against various indicators greater bioactivity score. 161 common targets obtained followed by compound-target construction protein–protein interaction, which showed role diverse biological system. Top hub genes TLR4, MMP9, MAPK14, AKT1, VEGFA HSP90AA1 respective associates. Higher binding affinities three Flavan-3-ol −7.1, −9.0 −8.0 kcal/mol, respectively. The MD simulation results validate structural flexibility two complexes Flavan-MMP9 Germich-TLR4 no. hydrogen bonds, root mean square deviations energies. concluded that C. (Dihydrokaempferol, Flavan-3-ol) (Germichrysone) have potential therapeutic constituents treat future drug formulation. Graphical

Language: Английский

Citations

6
Lessons Learnt from COVID-19: Computational Strategies for Facing Present and Future Pandemics DOI Open Access
Matteo Pavan, Stefano Moro

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4401 - 4401

Published: Feb. 23, 2023

Since its outbreak in December 2019, the COVID-19 pandemic has caused death of more than 6.5 million people around world. The high transmissibility causative agent, SARS-CoV-2 virus, coupled with potentially lethal outcome, provoked a profound global economic and social crisis. urgency finding suitable pharmacological tools to tame shed light on ever-increasing importance computer simulations rationalizing speeding up design new drugs, further stressing need for developing quick reliable methods identify novel active molecules characterize their mechanism action. In present work, we aim at providing reader general overview pandemic, discussing hallmarks management, from initial attempts drug repurposing commercialization Paxlovid, first orally available drug. Furthermore, analyze discuss role computer-aided discovery (CADD) techniques, especially those that fall structure-based (SBDD) category, facing future pandemics, by showcasing several successful examples campaigns where commonly used such as docking molecular dynamics have been employed rational effective therapeutic entities against COVID-19.

Language: Английский

Citations

13
Systematic review and meta-analysis of Tuberculosis and COVID-19 Co-infection: Prevalence, fatality, and treatment considerations DOI Creative Commons
Quan Wang, Yanmin Cao, Xinyu Liu

et al.

PLoS neglected tropical diseases, Journal Year: 2024, Volume and Issue: 18(5), P. e0012136 - e0012136

Published: May 13, 2024

Background Tuberculosis (TB) and COVID-19 co-infection poses a significant global health challenge with increased fatality rates adverse outcomes. However, the existing evidence on epidemiology treatment of TB-COVID remains limited. Methods This updated systematic review aimed to investigate prevalence, rates, outcomes co-infection. A comprehensive search across six electronic databases spanning November 1, 2019, January 24, 2023, was conducted. The Joanna Briggs Institute Critical Appraisal Checklist assessed risk bias included studies, meta-analysis estimated relative risk. Results From 5,095 studies screened, 17 were included. prevalence reported in 38 countries or regions, both high low TB areas. Prevalence estimates approximately 0.06% West Cape Province, South Africa, 0.02% California, USA. Treatment approaches for displayed minimal evolution since 2021. Converging findings from diverse underscored hospitalization risks, extended recovery periods, accelerated mortality compared single cases. pooled rate among co-infected patients 7.1% (95%CI: 4.0% ~ 10.8%), slightly lower than previous estimates. In-hospital faced mean 11.4% 5.6% 18.8%). in-hospital 0.8 (95% CI, 0.18–3.68) versus COVID patients. Conclusion is increasingly prevalent worldwide, gradually declining but remaining higher alone. underscores urgency continued research understand address challenges posed by

Language: Английский

Citations

5
Cardiovascular Symposium on Perspectives in Long COVID DOI Creative Commons

Robert S. Dieter,

Prakasha Kempaiah, Elizabeth G. Dieter

et al.

Clinical and Applied Thrombosis/Hemostasis, Journal Year: 2025, Volume and Issue: 31

Published: Jan. 1, 2025

Significant progress has been made in treating Coronavirus disease (COVID) – an infectious caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). An ominous turn pandemic is evolving public health crisis emanating from persistent SARS-CoV-2 infection and its associated long-term impact. Long COVID or post–COVID describes protean symptoms that persist at least 3 months after onset of illness last for individuals with a history confirmed infection. become concern. Millions infected are now facing chronic multi-organ failures, including neuropsychiatric, cardiovascular, pulmonary, kidney complications. In general, cause long unclear but factors such as prolonged activation immune responses, viral persistence triggering transcription dysregulation genes normal thrombotic may play role cardiovascular Although inflammatory biomarkers reported other disorders, it remains whether similar manifestations following COVID. Medications sulodexide directed glycocalyx coagulation have demonstrated benefits smaller studies. Here, we describe outcomes symposium on underlying mechanisms

Language: Английский

Citations

0
Artificial intelligence in tumor drug resistance: Mechanisms and treatment prospects DOI
Jianyou Gu, Junfeng Zhang,

Silüe Zeng

et al.

Published: Feb. 1, 2025

Language: Английский

Citations

0
Molecular docking and dynamics simulation study of medicinal fungi derived secondary metabolites as potential inhibitor for COVID-19 treatment DOI Creative Commons
Md Abu Sayem Khan,

Md Ibrahim Miah,

Zahidul Islam

et al.

Informatics in Medicine Unlocked, Journal Year: 2023, Volume and Issue: 41, P. 101305 - 101305

Published: Jan. 1, 2023

The severity of COVID-19, lack specific treatment, and controversies on the vaccine's efficacy demand development new drugs against SARS-CoV-2. Fungi produce various metabolites with diverse molecular structures that have emerged as promising antiviral drug candidates. Therefore, present study aimed to investigate medicinal fungi derived secondary potential inhibitors 3 different targets associated viral entry (human TMPRSS2) replication (main papain-like protease) through docking dynamic simulation studies. Based our findings, we identified Phelligridin E, Lepiotaprocerine G, Inoscavin A blockers SARS-CoV-2 main protease, human TMPRSS2, respectively. These compounds strongly interacted their corresponding target, passed Lipinski Rule's had acceptable ADMET properties. Drug-protein complexes showed good stability during MD simulation. Estimation binding free energy using MM-GBSA method validated inhibitor compounds. Taken together, believe further in vitro vivo investigations proposed molecules may contribute expanding therapeutic arsenal fight COVID-19.

Language: Английский

Citations

9
Interaction between host G3BP and viral nucleocapsid protein regulates SARS-CoV-2 replication DOI Creative Commons
Zemin Yang, Bryan A. Johnson, Victoria Meliopoulos

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: June 30, 2023

Abstract G3BP1/2 are paralogous proteins that promote stress granule formation in response to cellular stresses, including viral infection. prominent interactors of the nucleocapsid (N) protein severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, functional consequences G3BP1-N interaction context infection remain unclear. Here we used structural and biochemical analyses define residues required for interaction, followed by structure-guided mutagenesis G3BP1 N selectively reciprocally disrupt their interaction. We found mutation F17 within led selective loss with consequent failure assembly. Introduction SARS-CoV-2 bearing an F17A resulted a significant decrease replication pathogenesis vivo, indicating promotes suppressing ability form granules.

Language: Английский

Citations

7
PDE5 inhibitors against cancer via mediating immune cells in tumor microenvironment: AI‐based approach for future drug repurposing exploration DOI Creative Commons
Zhenzhan Zhang,

Donghua Huang,

Junjie Feng

et al.

Deleted Journal, Journal Year: 2024, Volume and Issue: 2(3)

Published: March 16, 2024

Abstract Phosphodiesterase‐5 (PDE5) inhibitors are used clinically for the treatment of erectile dysfunction, pulmonary arterial hypertension, and other urological diseases. Emerging evidences have suggested therapeutic capacity PDE5 as repurposed drugs in oncology. However, essential immune function against cancer tumor microenvironment (TME) remains unclear. This review aimed to summarize recent advances regarding repurposing anti‐cancer agents management enhance anti‐tumor response by mediating various cells, which included myeloid‐derived suppressor macrophages, T fibroblasts, natural killer cells TME. Moreover, artificial intelligence (AI), a new approach, is composed traditional machine learning deep methods could be potentially identify targets TME predict efficacy drug toward malignancies. In summary, these endeavors provide novel insights into comprehensive strategies AI‐based approach future exploration.

Language: Английский

Citations

2