Abstract
Rationale: The first influenza pandemic of 21st century was attributed to a novel quadruple reassortant H1N1 virus that emerged in 2009. Currently available therapies for influenza have drugresistant. Therefore, there is a need to develop new generation immunotherapeutic antiviral strategy. This study described the efficacy of a novel bifunctional immunostimulatory siRNAs against H1N1pdm swine flu virus by targeting the Nucleocapsid (NP) gene. Methods & Findings: Small interfering RNAs (siRNA) targeting conserved region of NP were screened for antiviral efficacy in human lung epithelial cells (A549). Further, a bifunctional siRNA was synthesized by combining immunostimulatory sequence (5’-UGUGU-3’) with NP specific siRNA. This immunostimulatory siRNA (NP-1-is) revealed strong antiviral effect through reduction in mRNA copies (99.58%), reduction in virus associated cell apoptosis and inhibition of nucleocapsid protein in western blot. This immunostimulatory siRNA was found more effective than nontagged siRNA. Further studies including dose dependent and time course kinetics revealed that the NP-1-is siRNA is more effective at 20-80 nM with significant protection upto 48 hpi. Besides, the qRT-PCR and western blot analysis confirmed higher antiviral response of immunostimulatory siRNA was due to upregulation of TLR-7 MyD88, IRF-7 and IFN-α. Conclusions: This study paves the way for broad-spectrum RNAi-based therapeutics using immunostimulatory motif towards improved antiviral effect. Hence this approach will be useful to confront the sudden emergence of pandemic strains.
Keywords: Antiviral activity, Bifunctional siRNA, Small interfering RNAs (siRNA), Swine flu (H1N1) virus.
Call for Papers in Thematic Issues
Melatonin Signaling in Health and Disease
Melatonin regulates a multitude of physiological functions, including circadian rhythms, acting as a scavenger of free radicals, an anti-inflammatory agent, a modulator of mitochondrial homeostasis, an antioxidant, and an enhancer of nitric oxide bioavailability. AANAT is the rate-limiting enzyme responsible for converting serotonin to NAS, which is further converted to ...read more
Programmed Cell Death Genes in Oncology: Pioneering Therapeutic and Diagnostic Frontiers.
Programmed cell death (PCD) is recognized as a pivotal biological mechanism with far-reaching effects in the realm of cancer therapy. This complex process encompasses a variety of cell death modalities, including apoptosis, autophagic cell death, pyroptosis, and ferroptosis, each of which contributes to the intricate landscape of cancer development and ...read more
The now and future of gene transfer technologies
Gene and cell therapies rely on a gene delivery system which is safe and effective. Both viral and non-viral vector systems are available with specific pros and cons. The choice of a vector system is largely dependent on the application which is a balance between target tissue/disease and safety, efficacy ...read more
Related Books
Decolorization by Thanatephorus Cucumeris Dec 1
Industrial Applications of Soil Microbes
The Future of Agriculture: IoT, AI and Blockchain Technology for Sustainable Farming
Handbook of Integrated Weed Management for Major Field Crops
Practical Biochemistry
Anticancer Drugs Sourced from Marine Life
Opportunities for Biotechnology Research and Entrepreneurship
Diseases of Ornamental, Aromatic and Medicinal Plants
Diabetes and Breast Cancer: An Analysis of Signaling Pathways
Fundamentals of Cellular and Molecular Biology
44
2
1
1