Exploration of comprehensive marine natural products database against dengue viral non-structural protein 1 using high-throughput computational studies

Abstract

Dengue virus (DENV) non-structural protein 1 (NS1) is a versatile quasi-protein essential for the multiplication of the virus. This study applied high-throughput virtual screening (HTVS) and molecular dynamics (MD) simulation to detect the potential marine natural compounds against the NS1 of DENV. The structure of the NS1 protein was retrieved from Protein Data Bank with (PDB ID: 4O6B). Missing residues were added using modeler software. Molecular operating environment (MOE) programme was used to prepare the protein before docking. Virtual screening was performed on PyRx software to identify natural compounds retrieved from Comprehensive Marine Natural Products Database (CMNPD) against the NS1 protein, and best-docked compounds were examined by molecular docking and molecular dynamic (MD) simulation. Out of 31,561 marine compounds, the top 10 compounds showed docking scores lesser than −8.0 kcal/mol. One of the best hit compounds, CMNPD6802, was further analyzed using MD simulation study at 100 nanoseconds and Molecular Mechanics with Generalized Born and Surface Area Solvation (MM/GBSA). Based on its total binding energy, determined using the MM/GBSA approach, CMNPD6802 was ranked first. Its pharmacokinetic properties concerning the target protein NS1 were also evaluated. The results of the MD simulation showed that CMNPD6802 remained in close contact with the protein throughout the activation period, mapped using principal component analysis. These findings suggest that CMNPD6802 could serve as an NS1 inhibitor and may be a potential candidate for treating DENV infections.

Communicated by Ramaswamy H. Sarma

Keywords:

• ADMET analysis
• dengue virus
• high-throughput virtual screening
• marine compounds
• molecular docking
• NS1 protein

Authors’ contributions

BAB, AA, VV, ML – conception and design; BAB, AA, VV, NAQ – acquisition, analysis, interpretation of data; NAK, THD, SAD – software used in the work; NAK, THD, SAD, ML – initial draft and revision. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

The authors report no competing interests.

Data availability statement

The data presented in this study are available on request from the corresponding author.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by the Deputyship for Research and Innovation, Ministry of Education in Saudi Arabia, under Grant number ISP22-1.