دورية أكاديمية
Inhibition of early RNA replication in Chikungunya and Dengue virus by lycorine: In vitro and in silico studies.
| العنوان: | Inhibition of early RNA replication in Chikungunya and Dengue virus by lycorine: In vitro and in silico studies. |
|---|---|
| المؤلفون: | Agrawal T; Centre for Immunobiology and Immunotherapy, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad, 121001, Haryana, India; Centre for Virus Research, Therapeutics and Vaccines, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad, 121001, Haryana, India. Electronic address: tanvi@thsti.res.in., Siddqui G; Centre for Virus Research, Therapeutics and Vaccines, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad, 121001, Haryana, India., Dahiya R; Computational Biophysics and CADD Group, Computational and Mathematical Biology Centre (CMBC), Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad, 121001, Haryana, India., Patidar A; Centre for Immunobiology and Immunotherapy, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad, 121001, Haryana, India., Madan U; Centre for Immunobiology and Immunotherapy, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad, 121001, Haryana, India., Das S; Centre for Virus Research, Therapeutics and Vaccines, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad, 121001, Haryana, India., Asthana S; Computational Biophysics and CADD Group, Computational and Mathematical Biology Centre (CMBC), Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad, 121001, Haryana, India., Samal S; Centre for Virus Research, Therapeutics and Vaccines, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad, 121001, Haryana, India., Awasthi A; Centre for Immunobiology and Immunotherapy, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad, 121001, Haryana, India. Electronic address: aawasthi@thsti.res.in. |
| المصدر: | Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Oct 20; Vol. 730, pp. 150393. Date of Electronic Publication: 2024 Jul 11. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2104 (Electronic) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2002- >: San Diego, CA : Elsevier Original Publication: New York, Academic Press. |
| مواضيع طبية MeSH: | Amaryllidaceae Alkaloids*/pharmacology , Amaryllidaceae Alkaloids*/chemistry , Antiviral Agents*/pharmacology , Antiviral Agents*/chemistry , Chikungunya virus*/drug effects , Chikungunya virus*/genetics , Dengue Virus*/drug effects , Dengue Virus*/genetics , Phenanthridines*/pharmacology , Phenanthridines*/chemistry , RNA Replication*/drug effects , RNA, Viral*/genetics , RNA, Viral*/metabolism, Animals ; Humans ; Cell Line ; Chlorocebus aethiops ; Computer Simulation ; Molecular Docking Simulation |
| مستخلص: | Arboviruses such as chikungunya virus (CHIKV) and dengue virus (DENV) collectively afflict millions of individuals worldwide particularly in endemic countries like India, leading to substantial morbidity and mortality. With the lack of effective vaccines for both CHIKV and DENV in India, the search for antiviral compounds becomes paramount to control these viral infections. In line with this, our investigation was focused on screening natural compounds for their potential antiviral activity against CHIKV and DENV. Using different assays, including plaque assay, immunofluorescence, and reverse transcription-quantitative real-time PCR (qRT-PCR), out of 109 natural compounds tested, we confirmed lycorine's in vitro antiviral activity against CHIKV and DENV at low micromolar concentrations in different cell types. Time of addition assays indicated that lycorine does not impede viral entry. Additionally, qRT-PCR results along with time of addition assay suggested that lycorine interferes with the synthesis of negative strand viral RNA. Molecular docking analysis was done to understand the mode of inhibition of viral replication. The results revealed that the most likely binding site with the highest binding affinity of lycorine, was at the palm and finger domains, in the vicinity of the catalytic site of CHIKV and DENV RNA-dependent RNA polymerase (RdRp). Collectively, our data underscores the potential of lycorine to be developed as a direct acting inhibitor for DENV and CHIKV, addressing the critical need of requirement of an antiviral in regions where these viruses pose significant public health threats. Competing Interests: Declaration of competing interest None. (Copyright © 2024 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Antiviral; Chikungunya; Dengue; Lycorine; Natural product; RNA dependent RNA polymerase |
| المشرفين على المادة: | 0 (Amaryllidaceae Alkaloids) 0 (Antiviral Agents) I9Q105R5BU (lycorine) 0 (Phenanthridines) 0 (RNA, Viral) |
| تواريخ الأحداث: | Date Created: 20240714 Date Completed: 20240819 Latest Revision: 20240821 |
| رمز التحديث: | 20240822 |
| DOI: | 10.1016/j.bbrc.2024.150393 |
| PMID: | 39003865 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1090-2104 |
|---|---|
| DOI: | 10.1016/j.bbrc.2024.150393 |