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Cellular uptake of metal oxide-based nanocomposites and targeting of chikungunya virus replication protein nsP3
Affiliation:1. Department of Chemistry, Indian Institute of Technology Roorkee, Uttarakhand, India;2. Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Uttarakhand, India;1. Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria;2. Department of Anatomy, College of Medicine, University of Ibadan, Ibadan, Nigeria;3. Departamento de Bioquímica e Biologia Molecular, CCNE, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil;1. Department of Social Medicine, Graduate School of Medicine, Hirosaki University, Japan;2. School of Medicine, Hirosaki University, Japan;3. Department of Hematology, National Cancer Center Hospital, Japan;4. Center of Innovation, Research Initiatives Organization, Hirosaki University, Japan;1. Toxicology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran;2. Department of Toxicology, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran;3. Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran;4. Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran;1. Poursina Hakim Digestive Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran;2. Immunology Department, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran;3. University of Debrecen, Medical School Hungary, Egyetem tér 1, Debrecen;4. Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;5. Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran;6. Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India;7. Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Science, Chennai 602105, India;8. University Institute of Pharma Sciences, Chandigarh University, Mohali, Punjab, India;9. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran;10. Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;11. School of Medicine, The University of Western Australia, Perth, Australia;12. Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran;1. School of Public Health, Guangxi Medical University, Shuangyong Road No.22, Nanning 530021, Guangxi, China;2. School of Public Health, Guilin Medical University, 20 Lequn Road, Guilin, Guangxi, China;3. Guangxi key laboratory of Environmental Exposomics and Entire Lifecycle Health, China;4. Guangxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, Guangxi, China;5. Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Guangxi Medical University, Nanning 530021, China;6. Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, School of Public Health, Guangxi Medical University, Nanning 530021, China;7. Guangxi Key Laboratory of Environment and Health Research, Guangxi Medical University, Nanning 530021, China
Abstract:Emergence of new pathogenic viruses along with adaptive potential of RNA viruses has become a major public health concern. Therefore, it is increasingly crucial to investigate and assess the antiviral potential of nanocomposites, which is constantly advancing area of medical biology. In this study, two types of nanocomposites: Ag/NiO and Ag2O/NiO/ZnO with varying molar ratios of silver and silver oxide, respectively have been synthesised and characterised. Three metal/metal oxide (Ag/NiO) composites having different amounts of Ag nanoparticles (NPs) anchored on NiO octahedrons are AN-5 % (5 % Ag), AN-10 % (10 % Ag) and AN-15 % (15 % Ag)) and three ternary metal oxide nanocomposites (Ag2O/NiO/ZnO) i.e., A/N/Z-1, A/N/Z-2, and A/N/Z-3 with different molar ratios of silver oxide (10 %, 20 % and 30 %, respectively) were evaluated for their antiviral potential. Cellular uptake of nanocomposites was confirmed by ICP-MS. Intriguingly, molecular docking of metal oxides in the active site of nsP3 validated the binding of nanocomposites to chikungunya virus replication protein nsP3. In vitro antiviral potential of nanocomposites was tested by performing plaque reduction assay, cytopathic effect (CPE) analysis and qRT-PCR. The nanocomposites showed significant reduction in virus titre. Half-maximal inhibitory concentration (IC50) for A/N/Z-3 and AN-5 % were determined to be 2.828 and 3.277 µg/mL, respectively. CPE observation and qRT-PCR results were consistent with the data obtained from plaque reduction assay for A/N/Z-3 and AN-5 %. These results have opened new avenues for development of nanocomposites based antiviral therapies.
Keywords:Nanocomposite  Antivirals  CHIKV  Ternary metal oxides
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