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Exploring the antiviral inhibitory activity of Niloticin against the NS2B/NS3 protease of Dengue virus (DENV2).
Stalin, Antony; Han, Jiajia; Daniel Reegan, Appadurai; Ignacimuthu, Savarimuthu; Liu, Shuwen; Yao, Xingang; Zou, Quan.
Afiliación
  • Stalin A; Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu 610 054, China. Electronic address: antonystalin@uestc.edu.cn.
  • Han J; NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
  • Daniel Reegan A; National Centre for Disease Control, Bengaluru Branch, No. 8, NTI Campus, Bellary Road, Bengaluru 560 003, Karnataka, India; ICMR-Vector Control Research Centre, Indira Nagar, Gorimedu, Puducherry 605 006, India.
  • Ignacimuthu S; Xavier Research Foundation, St. Xavier's College, Affiliated to Manonmaniam Sundaranar University, Palayamkottai 627 002, Tamil Nadu, India.
  • Liu S; NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China; Key Laboratory of Infectious Diseases Research in South China (Southern Medical Univ
  • Yao X; NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China; Key Laboratory of Infectious Diseases Research in South China (Southern Medical Univ
  • Zou Q; Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu 610 054, China. Electronic address: zouquan@nclab.net.
Int J Biol Macromol ; 277(Pt 1): 133791, 2024 Oct.
Article en En | MEDLINE | ID: mdl-38992553
ABSTRACT
Dengue virus (DENV2) is the cause of dengue disease and a worldwide health problem. DENV2 replicates in the host cell using polyproteins such as NS3 protease in conjugation with NS2B cofactor, making NS3 protease a promising antiviral drug-target. This study investigated the efficacy of 'Niloticin' against NS2B/NS3-protease. In silico and in vitro analyses were performed which included interaction of niloticin with NS2B/NS3-protease, protein stability and flexibility, mutation effect, betweenness centrality of residues and analysis of cytotoxicity, protein expression and WNV NS3-protease activity. Similar like acyclovir, niloticin forms strong H-bonds and hydrophobic interactions with residues LEU149, ASN152, LYS74, GLY148 and ALA164. The stability of the niloticin-NS2B/NS3-protease complex was found to be stable compared to the apo NS2B/NS3-protease in structural deviation, PCA, compactness and FEL analysis. The IC50 value of niloticin was 0.14 µM in BHK cells based on in vitro cytotoxicity analysis and showed significant activity at 2.5 µM in a concentration-dependent manner. Western blotting and qRT-PCR analyses showed that niloticin reduced DENV2 protein transcription in a dose-dependent manner. Besides, niloticin confirmed the inhibition of NS3-protease by the SensoLyte 440 WNV protease detection kit. These promising results suggest that niloticin could be an effective antiviral drug against DENV2 and other flaviviruses.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antivirales / Serina Endopeptidasas / Proteínas no Estructurales Virales / Virus del Dengue Límite: Animals / Humans Idioma: En Revista: Int J Biol Macromol Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antivirales / Serina Endopeptidasas / Proteínas no Estructurales Virales / Virus del Dengue Límite: Animals / Humans Idioma: En Revista: Int J Biol Macromol Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos