A Computational Approach to Characterize the Protein S-Mer Tyrosine Kinase (PROS1-MERTK) Protein-Protein Interaction Dynamics DOI Creative Commons
Mak B. Djulbegovic, David J. Taylor Gonzalez,

Luciano Laratelli

et al.

Cell Biochemistry and Biophysics, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 13, 2024

Abstract Protein S (PROS1) has recently been identified as a ligand for the TAM receptor MERTK, influencing immune response and cell survival. The PROS1–MERTK interaction plays role in cancer progression, promoting evasion metastasis multiple cancers by fostering tumor-supportive microenvironment. Despite its importance, limited structural insights into this underscore need computational studies to explore their binding dynamics, potentially guiding targeted therapies. In study, we investigated using advanced analyses support immunotherapy research. High-resolution models from ColabFold, an AlphaFold2 adaptation, provided baseline structure, allowing us examine interface with ChimeraX map residue interactions through Van der Waals criteria. Molecular dynamics (MD) simulations were conducted GROMACS over 100 ns assess stability conformational changes RMSD, RMSF, radius of gyration ( R g). was predicted contain heterogeneous mix amino acid contacts, lysine leucine frequent participants. MD demonstrated prominent early shifts, stabilizing after approximately 50 small shifts occurring simulation completed. addition, there are various regions each protein that have greater fluctuations compared others, which may represent attractive areas target halt progression interaction. These deepen our understanding modulation tumor unveiling potential targets immunotherapy.

Language: Английский

Inhibition of nonstructural protein 15 of SARS‐CoV‐2 by golden spice: A computational insight DOI
Rahul Singh, Vijay Kumar Bhardwaj, Rituraj Purohit

et al.

Cell Biochemistry and Function, Journal Year: 2022, Volume and Issue: 40(8), P. 926 - 934

Published: Oct. 6, 2022

The quick widespread of the coronavirus and speedy upsurge in tally cases demand fast development effective drugs. uridine-directed endoribonuclease activity nonstructural protein 15 (Nsp15) is responsible for invasion host immune system. Therefore, developing potential inhibitors against Nsp15 a promising strategy. In this concern, silico approach can play significant role, as it cost-effective comparison to trial error approaches experimental investigations. study, six turmeric derivatives (curcuminoids) were chosen analysis. molecular interactions, pharmacokinetics, drug-likeness all curcuminoids measured. Further, stability Nsp15-curcuminoids complexes was appraised by employing dynamics (MD) simulations MM-PBSA approaches. All molecules affirmed have strong interactions pharmacokinetic profile. MD data stated that stable during simulations. showed high binding affinity, these could be admitted modulators inhibition.

Language: Английский

Citations

71
Multi‐target approach against SARS‐CoV‐2 by stone apple molecules: A master key to drug design DOI
Rahul Singh, Rituraj Purohit

Phytotherapy Research, Journal Year: 2023, Volume and Issue: 38(1), P. 7 - 10

Published: Feb. 14, 2023

Data S1: Supporting Information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by authors. Any queries (other than missing content) should be directed to corresponding author article.

Language: Английский

Citations

34
CADD-Based Discovery of Novel Oligomeric Modulators of PKM2 with Antitumor Activity in Aggressive Human Glioblastoma Models DOI Creative Commons

Maia Cabrera,

Romina Armando,

Ian Czarnowski

et al.

Heliyon, Journal Year: 2025, Volume and Issue: unknown, P. e42238 - e42238

Published: Jan. 1, 2025

Language: Английский

Citations

1
Enhanced sampling in molecular dynamics simulations and their latest applications—A review DOI
Wen‐Hui Shen, Tong Zhou, Xinghua Shi

et al.

Nano Research, Journal Year: 2023, Volume and Issue: 16(12), P. 13474 - 13497

Published: Dec. 1, 2023

Language: Английский

Citations

16
Identification of antiviral peptide inhibitors for receptor binding domain of SARS-CoV-2 omicron and its sub-variants: an in-silico approach DOI Open Access
Swati Singh, Hemanth Naick Banavath,

Priya Godara

et al.

3 Biotech, Journal Year: 2022, Volume and Issue: 12(9)

Published: Aug. 1, 2022

Language: Английский

Citations

19
Viral target and metabolism‐based rationale for combined use of recently authorized small molecule COVID‐19 medicines: Molnupiravir, nirmatrelvir, and remdesivir DOI Creative Commons

Daisy Yan,

Bingfang Yan

Fundamental and Clinical Pharmacology, Journal Year: 2023, Volume and Issue: 37(4), P. 726 - 738

Published: March 18, 2023

Abstract The COVID‐19 pandemic remains a major health concern worldwide, and SARS‐CoV‐2 is continuously evolving. There an urgent need to identify new antiviral drugs develop novel therapeutic strategies. Combined use of newly authorized medicines including molnupiravir, nirmatrelvir, remdesivir has been actively pursued. Mechanistically, nirmatrelvir inhibits replication by targeting the viral main protease (M pro ), critical enzyme in processing immediately translated coronavirus polyproteins for replication. Molnupiravir remdesivir, on other hand, inhibit RNA‐dependent RNA‐polymerase (RdRp), which directly responsible genome production subgenomic RNAs. targets RdRp induces severe RNA mutations (genome), commonly referred as error catastrophe. Remdesivir, contrast, causes chain termination arrests synthesis genome. In addition, all three undergo extensive metabolism with strong significance. hydrolytically activated carboxylesterase‐2 (CES2), inactivated cy tochrome P 450‐based oxidation (e.g., CYP3A4), CES1 but covalently CES2. Additionally, are oxidized same CYP enzymes. distinct mechanisms action provide rationale their combined use. On these that determines potential. This review discusses how pathways enzymes involved should be carefully considered during synergy.

Language: Английский

Citations

11
Influence of EGCG oxidation on inhibitory activity against the SARS-CoV-2 main protease DOI
Yufeng He,

Meng Hao,

Mingchuan Yang

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 274, P. 133451 - 133451

Published: June 27, 2024

Language: Английский

Citations

4
Harnessing Brazilian biodiversity database: identification of flavonoids as potential inhibitors of SARS-CoV-2 main protease using computational approaches and all-atom molecular dynamics simulation DOI Creative Commons
João Augusto Pereira da Rocha, Renato Araújo da Costa,

Andréia do Socorro Silva da Costa

et al.

Frontiers in Chemistry, Journal Year: 2024, Volume and Issue: 12

Published: Feb. 22, 2024

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is the etiological agent responsible for global outbreak of COVID-19 (Coronavirus Disease 2019). The main protease SARS-CoV-2, Mpro, a key enzyme that plays vital role in mediating viral replication and transcription. In this study, comprehensive computational approach was employed to investigate binding affinity, selectivity, stability natural product candidates as potential new antivirals acting on polyprotein processing mediated by Mpro. A library 288 flavonoids extracted from Brazilian biodiversity screened select Mpro inhibitors. An initial filter based Lipinski's rule five applied, 204 compounds did not violate any Lipinski rules were selected. then docked into active site using GOLD program, poses subsequently re-scored MM-GBSA (Molecular Mechanics Generalized Born Surface Area) free energy calculations performed AmberTools23. top with best values selected analysis their interactions residues protein. Next, we conducted toxicity drug-likeness analysis, non-toxic subjected molecular dynamics simulation calculation MM-PBSA Poisson-Boltzmann method. It observed had lower than co-crystal ligand. Furthermore, these also formed hydrogen bonds two important residues, Cys145 Glu166, Two passed showed stable conformations during simulations. Among these, NuBBE_867 exhibited value compared crystallographic inhibitor. Therefore, study suggests could be inhibitor against may further examined confirm our results.

Language: Английский

Citations

3
Dual Anti-Inflammatory and Anticancer Activity of Novel 1,5-Diaryl Pyrazole Derivatives: Molecular Modeling, Synthesis, In Vitro Activity, and Dynamics Study DOI Creative Commons

D. Priya,

S. M. Esther Rubavathy,

J. Narayanan

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(4), P. 788 - 788

Published: April 3, 2024

A series of novel 1,5-diaryl pyrazole derivatives targeting the COX enzyme were designed by combined ligand and structure-based approach. The molecules then further subjected to ADMET molecular docking studies. Out 34 compounds, top-10 from computation studies synthesized, characterized, evaluated for COX-2 inhibition anti-cancer activity. Initially, target compounds screened protein denaturation assay. results top-five T2, T3, T5, T6, T9 in vitro enzymatic assay As far as inhibitory activity is considered, two T3 exhibited half maximum concentration (IC

Language: Английский

Citations

3
Targeting the SARS-CoV-2 HR1 with Small Molecules as Inhibitors of the Fusion Process DOI Open Access
Davide Gentile, Alessandro Coco, Vincenzo Patamia

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(17), P. 10067 - 10067

Published: Sept. 3, 2022

The rapid and global propagation of the novel human coronavirus that causes severe acute respiratory syndrome 2 (SARS-CoV-2) has produced an immediate urgency to discover promising targets for treatment this virus. In paper, we studied spike protein S2 domain SARS-CoV-2 as it is most conserved component controls crucial fusion process a target different databases small organic compounds. Our in silico methodology, based on pharmacophore modeling, docking simulation molecular dynamics simulations, was first validated with ADS-J1, potent small-molecule HIV inhibitor already proved effective binding HR1 inhibiting core SARS-CoV-1. It then focused finding molecules new peptides inhibitors. methodology identified several potential inhibitors process. Among these, NF 023 hydrate (MolPort-006-822-583) one best-scored Other compounds interest are ZINC00097961973, Salvianolic acid, Thalassiolin A marine_160925_88_2. Two interesting active were also identified: AP00094 (Temporin A) AVP1227 (GBVA5). inhibition valid inhibit virus entry cells. discussed reported paper led encouraging results future vitro tests against SARS-CoV-2.

Language: Английский

Citations

16