In search of suitable protein targets for anti-malarial and anti-dengue drug discovery

Nguyen, Phung Kim Phi; Nguyen, Giang Le Tra; ThiĐinh, Oanh; Duong, Cuong Quoc; Nguyen, Lam; Truong, Thanh N.

doi:10.1016/j.molstruc.2022.132520

Cited by 7 publications

(3 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar geometrical analysis have been reported on the docked complex of quinoline derivative with M pro of SARS-CoV-2 using snapshots by Singh et al [56]. Also, Nguyen et al have studied the druggable targets of dengue and malaria using multiple frames at different times during MDS [57]. The snapshots have revealed that the active site of the protein is capable of holding the docked ligand for sufficient time, which could lead to the disruption or deceleration of metabolic reactions.…”

Section: Geometrical Stability Of Complexessupporting

confidence: 61%

nCoV-19 therapeutics using cucurbitacin I structural derivatives: an in silico approach

Shrestha,

Marasini,

Subin

2024

Futur J Pharm Sci

View full text Add to dashboard Cite

Background Cucurbitacins are present in some common vegetables as secondary metabolites and are used by the plants against harmful microbes. Exploration of this capability of natural product based substances against wide variety of microbes seems relevant due to the ease of availability of the resources and safety. In this regard, considering the current pandemic, the antiviral properties of these molecules with a subset of Cucurbitacin I structural derivatives have been screened. The inhibition potential of the phytochemicals was assessed by the stability of the protein–ligand complex formed with the nucleocapsid protein (PDB ID: 7CDZ) of SARS-CoV-2 by computational methods. The proposition of an alternate antiviral candidate that is cost-effective and efficient relative to existing formulations is the main objective of this work. Results Server-based molecular docking experiments revealed CBN19 (PubChem CID: 125125068) as a hit candidate among 101 test compounds, a reference molecule (K31), and 5 FDA-approved drugs in terms of binding affinities sorted out based on total energies. The molecular dynamics simulations (MDS) showed moderate stability of the protein-CBN19 complex as implied by various geometrical parameters RMSD, Rg, RMSF, SASA and hydrogen bond count. The ligand RMSD of 3.0 ± 0.5 Å, RMSF of Cα of protein with less than 5 Å, and smooth nature of SASA and Rg curves were calculated for the adduct. The binding free energy (− 47.19 ± 6.24 kcal/mol) extracted from the MDS trajectory using the MMGBSA method indicated spontaneity of the reaction between CBN19 and the protein. The multiple ADMET studies of the phytochemicals predicted some drug-like properties with minimal toxicity that mandate experimental verification. Conclusions Based on all the preliminary in silico results, Cucurbitacin, CBN19 could be proposed as a potential inhibitor of nucleocapsid protein theoretically capable of curing the disease. The proposed molecule is recommended for further in vitro and in vivo trials in the quest to develop effective and alternate therapeutics from plant-based resources against COVID-19.

show abstract

Section: Geometrical Stability Of Complexessupporting

confidence: 61%

nCoV-19 therapeutics using cucurbitacin I structural derivatives: an in silico approach

Shrestha,

Marasini,

Subin

2024

Futur J Pharm Sci

View full text Add to dashboard Cite

show abstract

“…In 2022, Nguyen and co-workers conducted the studies in order to search promising anti-malarial target using molecular docking and MD simulations and identified plasmepsin (PDB ID: 1LEE) as one of the key target. [79] Herein, the MD simulations of 100 ns were executed using GROMACS 2020.01 software and CHARMM27 as the force field to study interactions and flexibility of co-crystallised ligand RS367 inside the binding site of the protein. The conformational structures of protein were recorded every 20 ns and the resultant values were analysed using the stability parameters including RMSD, RMSF, RoG and SASA.…”

Section: Molecular Dynamics Simulations In Search Of Anti-plasmodial ...mentioning

confidence: 99%

Recent Advancements and Developments of Molecular Dynamics Simulations in the Discovery of Anti‐protozoal Agents

Dhameliya,

Vekariya,

Vaddoriya

et al. 2024

ChemistrySelect

View full text Add to dashboard Cite

Molecular dynamics simulations have been developed as the most powerful tool in the field of computational chemistry for the discovery of novel anti‐protozoal agents against malaria. In this review, the recent advancements and developments in the field of molecular dynamics simulations driven identification and optimization of promising anti‐protozoal agents have been highlighted along with the use of advanced simulation softwares, energy calculations, stability parameters, and many more. To the best of our knowledge, the present work has been the first review article to highlight the use of molecular dynamics simulations for the discovery of anti‐plasmodial agents with the aim to dig out the significant insights into the simulations having the applications for the benefit of computational and medicinal chemists.

show abstract

“…Therefore, only these ligands were taken forward for MD studies. [42][43][44][45] Vdw: Van der Waals, HB: Conventional Hydrogen Bond, CHB: Carbon Hydrogen Bond.…”

Section: Hydrogen Bond Analysismentioning

confidence: 99%

Identifying Potential Drug Candidates against Plasmodium falciparum (Isolate 3D7) through Targeting ADP-dependent DNA Helicase RecQ: An in silico Approach

Ahsan,

Mallick

2023

Ind. J. Pharm. Edu. Res

View full text Add to dashboard Cite

Background:The malarial scenario has significantly varied in the past few decades; whether it is funding or the range of sophisticated life-saving tools that have been improved, the disease burden has reduced, and even a few nations are on the verge of their elimination. Despite these, drug resistance is the major hurdle in the fight against malaria. Aim: Identifying new drug candidates with negligible toxicity are imperative to overcome the existing problem. The proposed study aims to identify new potential lead molecules via targeting the ADP-dependent DNA helicase RecQ of Plasmodium falciparum (isolate 3D7) using Target-Based Virtual Screening (TBVS), molecular docking, and dynamics simulations. Materials and Methods: Ligand molecules were retrieved from a comprehensive digital library of the MCULE database having millions of investigational compounds. Pfizer's rule of five and the number of halogen atoms (3-5) were considered the basic primary filters of TBVS. The AutoDockVina (ADV) and GROningenMAchine for Chemical Simulations software were used to assess the molecular interactions and stability of protein-ligand complexes, respectively. Results: The primary filters of the TBVS work-pipeline depicted 2,597,040 chemical hits from over a hundred million small molecules. The toxicity tool sifted twenty-one molecules whose HIA and BBB permeation were evaluated through the Egan-Egg model. Five ligand hits were shortlisted with zero violation of drug-likeness and contain three or more hydrogen bonds. ADME, docking, and MD parameters depicted a molecule MCULE-1255186442-0-1 as a promising drug candidate. Conclusion: Druggable properties of identified ligands are inferred purely from the in silico experiments, so before its therapeutic implications, wet-lab validations are imperative.

show abstract

In search of suitable protein targets for anti-malarial and anti-dengue drug discovery

Cited by 7 publications

References 41 publications

nCoV-19 therapeutics using cucurbitacin I structural derivatives: an in silico approach

nCoV-19 therapeutics using cucurbitacin I structural derivatives: an in silico approach

Recent Advancements and Developments of Molecular Dynamics Simulations in the Discovery of Anti‐protozoal Agents

Identifying Potential Drug Candidates against Plasmodium falciparum (Isolate 3D7) through Targeting ADP-dependent DNA Helicase RecQ: An in silico Approach

Contact Info

Product

Resources

About