Phenol and chromone compounds for in silico inhibition of nsP2 and nsP3 of Chikungunya virus

Abstract

The rising concern about neglected tropical diseases imposes a global challenge, in this sense, this work brings 12 potential candidates based on chromone and phenol compounds to inhibit nsP2 and nsP3 of the Chikungunya virus (CHIKV), through molecular docking and ADMET evaluation. The molecular docking simulations for the nsP2 showed mild binding, in the nsP3 all the derivatives presented -6kcal/mol binding affinity and interacts with crucial residues in the replication cycle of CHIKV, the 5 best were chosen as the main derivatives for absorption, distribution, metabolism, excretion and toxicity (ADMET) evaluation). The ADMET results show high drug-likeness values, with good oral and intestinal absorption, excretion, distribution and toxicity, with moderate (Der9 to Der12) and poor (Der8) metabolism. Therefore, the 5 derivatives are potential candidates to treat chikungunya.

Keywords

Molecular docking / Neglected tropical disease / Chikungunya virus / Natural products / Daldinia

CRediT authorship contribution statement

Joan Petrus Oliveira Lima: Methodology, Formal analysis, Data curation. Caio Henrique Alexandre Roberto: Software, Methodology, Investigation. Matheus Nunes da Rocha: Software, Methodology, Investigation, Formal analysis. Victor Moreira de Oliveira: Investigation, Formal analysis, Data curation, Conceptualization. Rafael Melo Freire: Visualization, Resources. Ralph Santos-Oliveira: Visualization, Resources, Funding acquisition. Emmanuel Silva Marinho: Writing review & editing, Writing - original draft, Validation, Supervision, Conceptualization. Pedro de Lima Neto: Visualization, Validation, Supervision. Pierre Basílio Almeida Fechine: Writing - review & editing, Visualization, Supervision, Project administration.

Ethics approval

Not applicable.

Declaration of generative AI

The Authors declare that no generative AI have been used throughout the entire writing process of this manuscript.

Funding information

This work was supported by CNPq (308452/2022-4), CAPES (Finance Code 001- PROEX 23038.000509/2020-82) and Fondecyt 11200425, 124117 and AFB220001.

Data availability

The following softwares and webservers were used: PubChem (http s://pubchem.ncbi.nlm.nih.gov/), PDB nsP2 (https://www.rcsb.org/structure/3TRK), PDB nsP3 (https://www.rcsb.org/structure/3GPG), AutoDock Vina (https://vina.scripps.edu/), DoGSiteScorer (htt ps://proteins.plus/), AutoDock Tools (https://autodocksuite.scripps.edu/adt/), MarvinSketch (https://chemaxon.com/marvin), ADMETlab 2.0 (https://admetmesh.scbdd.com/), ADMETboost (https://ai-druglab.smu.edu/admet), SwissADME (http://www.swissadme.ch/), AI Drug Lab (https://ai-druglab.smu.edu/), XenoSite (https://xenosite.org/), pkCSM (https://biosig.lab.uq.edu.au/pkcsm/), ProTox II (https://tox-new.charite.de/protox_II/).

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

The authors would like to thank to the Universidade Estadual do Ceará - UECE, the Laboratório de Bioprospecção e Monitoramento de Recursos Naturais - LBMRN and Núcleo de Estudos Ambientais - NEA. The authors used resources of the Centro Nacional de Processamento de Alto Desempenho da UFC (CENAPAD - UFC), that was essential for this work, for which the authors are grateful.

Appendix A. Supplementary data

Supplementary data to this article can be found online at https://doi.org/10.1016/j.pscia.2025.100084.

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