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Mechanism of artemisinin resistance for malaria PfATP6 L263 mutations and discovering potential antimalarials: An integrated computational approach.

التفاصيل البيبلوغرافية
العنوان: Mechanism of artemisinin resistance for malaria PfATP6 L263 mutations and discovering potential antimalarials: An integrated computational approach.
المؤلفون: N N; School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong., C GP; School of Biosciences and Technology, VIT University, Vellore 632014, Tamil Nadu 632014, India., Chakraborty C; Department of Bioinformatics, School of Computer and Information Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India., V K; School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong., D TK; School of Biosciences and Technology, VIT University, Vellore 632014, Tamil Nadu 632014, India., V B; Department of Clinical Microbiology, Christian Medical College, Vellore 632014, Tamil Nadu, India., R S; School of Biosciences and Technology, VIT University, Vellore 632014, Tamil Nadu 632014, India., Lu A; School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong., Ge Z; School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong., Zhu H; School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
المصدر: Scientific reports [Sci Rep] 2016 Jul 29; Vol. 6, pp. 30106. Date of Electronic Publication: 2016 Jul 29.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: Antimalarials/*pharmacology , Artemisinins/*pharmacology , Calcium-Transporting ATPases/*genetics , Drug Resistance/*drug effects , Drug Resistance/*genetics , Malaria, Falciparum/*drug therapy , Mutation/*drug effects, Humans ; Molecular Docking Simulation/methods ; Mutant Proteins/genetics ; Mutation/genetics ; Plasmodium falciparum/drug effects ; Plasmodium falciparum/genetics ; Protein Binding/drug effects ; Protein Binding/genetics
مستخلص: Artemisinin resistance in Plasmodium falciparum threatens global efforts in the elimination or eradication of malaria. Several studies have associated mutations in the PfATP6 gene in conjunction with artemisinin resistance, but the underlying molecular mechanism of the resistance remains unexplored. Associated mutations act as a biomarker to measure the artemisinin efficacy. In the proposed work, we have analyzed the binding affinity and efficacy between PfATP6 and artemisinin in the presence of L263D, L263E and L263K mutations. Furthermore, we performed virtual screening to identify potential compounds to inhibit the PfATP6 mutant proteins. In this study, we observed that artemisinin binding affinity with PfATP6 gets affected by L263D, L263E and L263K mutations. This in silico elucidation of artemisinin resistance enhanced the identification of novel compounds (CID: 10595058 and 10625452) which showed good binding affinity and efficacy with L263D, L263E and L263K mutant proteins in molecular docking and molecular dynamics simulations studies. Owing to the high propensity of the parasite to drug resistance the need for new antimalarial drugs will persist until the malarial parasites are eventually eradicated. The two compounds identified in this study can be tested in in vitro and in vivo experiments as possible candidates for the designing of new potential antimalarial drugs.
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المشرفين على المادة: 0 (ATP6 protein, Plasmodium falciparum)
0 (Antimalarials)
0 (Artemisinins)
0 (Mutant Proteins)
EC 7.2.2.10 (Calcium-Transporting ATPases)
تواريخ الأحداث: Date Created: 20160730 Date Completed: 20180410 Latest Revision: 20191210
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC4965867
DOI: 10.1038/srep30106
PMID: 27471101
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/srep30106