Your browser doesn't support javascript.
loading
Identification of potential inhibitors targeting yellow fever virus helicase through ligand and structure-based computational studies.
Zaib, Sumera; Rana, Nehal; Ali, Hafiz Saqib; Ur Rehman, Mujeeb; Awwad, Nasser S; Ibrahium, Hala A; Khan, Imtiaz.
Afiliación
  • Zaib S; Department of Basic and Applied Chemistry, Faculty of Science and Technology, University of Central Punjab, Lahore, Pakistan.
  • Rana N; Department of Basic and Applied Chemistry, Faculty of Science and Technology, University of Central Punjab, Lahore, Pakistan.
  • Ali HS; Chemistry Research Laboratory, Department of Chemistry and the INEOS Oxford Institute for Antimicrobial Research, University of Oxford, Oxford, UK.
  • Ur Rehman M; Department of Basic and Applied Chemistry, Faculty of Science and Technology, University of Central Punjab, Lahore, Pakistan.
  • Awwad NS; Department of Chemistry, King Khalid University, Abha, Saudi Arabia.
  • Ibrahium HA; Biology Department, Faculty of Science, King Khalid University, Abha, Saudi Arabia.
  • Khan I; Manchester Institute of Biotechnology, The University of Manchester, Manchester, UK.
J Biomol Struct Dyn ; : 1-18, 2023 Dec 18.
Article en En | MEDLINE | ID: mdl-38109183
ABSTRACT
Yellow fever is a flavivirus having plus-sensed RNA which encodes a single polyprotein. Host proteases cut this polyprotein into seven nonstructural proteins including a vital NS3 protein. The present study aims to identify the most effective inhibitor against the helicase (NS3) using different advanced ligand and structure-based computational studies. A set of 300 ligands was selected against helicase by chemical structural similarity model, which are similar to S-adenosyl-l-cysteine using infiniSee. This tool screens billions of compounds through a similarity search from in-built chemical spaces (CHEMriya, Galaxi, KnowledgeSpace and REALSpace). The pharmacophore was designed from ligands in the library that showed same features. According to the sequence of ligands, six compounds (29, 87, 99, 116, 148, and 208) were taken for pharmacophore designing against helicase protein. Subsequently, compounds from the library which showed the best pharmacophore shared-features were docked using FlexX functionality of SeeSAR and their optibrium properties were analyzed. Afterward, their ADME was improved by replacing the unfavorable fragments, which resulted in the generation of new compounds. The selected best compounds (301, 302, 303 and 304) were docked using SeeSAR and their pharmacokinetics and toxicological properties were evaluated using SwissADME. The optimal inhibitor for yellow fever helicase was 2-amino-N-(4-(dimethylamino)thiazol-2-yl)-4-methyloxazole-5-carboxamide (302), which exhibits promising potential for drug development.Communicated by Ramaswamy H. Sarma.
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Biomol Struct Dyn Año: 2023 Tipo del documento: Article País de afiliación: Pakistán Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Biomol Struct Dyn Año: 2023 Tipo del documento: Article País de afiliación: Pakistán Pais de publicación: Reino Unido