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Pharmacophore-based virtual screening and in-silico study of natural products as potential DENV-2 RdRp inhibitors.
Roney, Miah; Huq, A K M Moyeenul; Issahaku, Abdul Rashid; Soliman, Mahmoud E S; Hossain, Md Sanower; Mustafa, Abu Hasnat; Islam, Md Alimul; Dubey, Amit; Tufail, Aisha; Mohd Aluwi, Mohd Fadhlizil Fasihi; Tajuddin, Saiful Nizam.
Afiliação
  • Roney M; Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang, Kuantan, Malaysia.
  • Huq AKMM; Bio Aromatic Research Centre, Universiti Malaysia Pahang, Kuantan, Malaysia;
  • Issahaku AR; Bio Aromatic Research Centre, Universiti Malaysia Pahang, Kuantan, Malaysia;
  • Soliman MES; School of Medicine, Department of Pharmacy, University of Asia Pacific, Dhaka, Bangladesh.
  • Hossain MS; West African Centre for Computational Analysis, Ghana.
  • Mustafa AH; Molecular Bio-computation and Drug Design Laboratory, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
  • Islam MA; West African Centre for Computational Analysis, Ghana.
  • Dubey A; Centre for Sustainability of Ecosystem and Earth Resources (Pusat ALAM), Universiti Malaysia Pahang, Kuantan, Malaysia;
  • Tufail A; Faculty of Science, Sristy College of Tangail, Tangail, Bangladesh.
  • Mohd Aluwi MFF; Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang, Kuantan, Malaysia.
  • Tajuddin SN; Department of Microbiology and Hygiene, Faculty of Veterinary Science, Bangladesh Agricultural University, Mymensingh, Bangladesh.
J Biomol Struct Dyn ; 41(21): 12186-12203, 2023.
Article em En | MEDLINE | ID: mdl-36645141
ABSTRACT
Dengue fever is a significant public health concern throughout the world, causing an estimated 500,000 hospitalizations and 20,000 deaths each year, despite the lack of effective therapies. The DENV-2 RdRp has been identified as a potential target for the development of new and effective dengue therapies. This research's primary objective was to discover an anti-DENV inhibitor using in silico ligand- and structure-based approaches. To begin, a ligand-based pharmacophore model was developed, and 130 distinct natural products (NPs) were screened. Docking of the pharmacophore-matched compounds were performed to the active site of DENV-2 RdRp protease . Eleven compounds were identified as potential DENV-2 RdRp inhibitors based on docking energy and binding interactions. ADMET and drug-likeness were done to predict their pharmacologic, pharmacokinetic, and drug-likeproperties . Compounds ranked highest in terms of pharmacokinetics and drug-like appearances were then subjected to additional toxicity testing to determine the leading compound. Additionally, MD simulation of the lead compound was performed to confirm the docked complex's stability and the binding site determined by docking. As a result, the lead compound (compound-108) demonstrated an excellent match to the pharmacophore, a strong binding contact and affinity for the RdRp enzyme, favourable pharmacokinetics, and drug-like characteristics. In summary, the lead compound identified in this study could be a possible DENV-2 RdRp inhibitor that may be further studied on in vitro and in vivo models to develop as a drug candidate.Communicated by Ramaswamy H. Sarma.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Produtos Biológicos / Farmacóforo Tipo de estudo: Diagnostic_studies / Prognostic_studies / Screening_studies Idioma: En Revista: J Biomol Struct Dyn Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Malásia

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Produtos Biológicos / Farmacóforo Tipo de estudo: Diagnostic_studies / Prognostic_studies / Screening_studies Idioma: En Revista: J Biomol Struct Dyn Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Malásia