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      Promising approaches for the treatment and prevention of viral respiratory illnesses

      research-article
      , MD, PhD a , b , , , PhD a , , MD b , , MSc c , , PhD a , , MD, PhD b
      The Journal of Allergy and Clinical Immunology
      American Academy of Allergy, Asthma & Immunology
      Influenza, bronchiolitis, common cold, respiratory syncytial virus, rhinovirus, vaccine, monoclonal, antiviral, natural products, public health, COPD, Chronic obstructive pulmonary disease, HA, Hemagglutinin, ICAM-1, Intercellular adhesion molecule 1, IFV, Influenza virus, NAI, Neuraminidase inhibitor, PIV, Parainfluenza Virus, RSV, Respiratory syncytial virus, RTI, Respiratory tract infection, SARS, Severe acute respiratory syndrome, SPM, Specialized proresolving lipid mediator, TLR, Toll-like receptor, VLP, Virus-like particle, vRTI, Viral respiratory tract infection

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          Abstract

          Viral respiratory tract infections are the most common human ailments, leading to enormous health and economic burden. Hundreds of viral species and subtypes have been associated with these conditions, with influenza viruses, respiratory syncytial virus, and rhinoviruses being the most frequent and with the highest burden. When considering prevention or treatment of viral respiratory tract infections, potential targets include the causative pathogens themselves but also the immune response, disease transmission, or even just the symptoms. Strategies targeting all these aspects are developing concurrently, and several novel and promising approaches are emerging. In this perspective we overview the entire range of options and highlight some of the most promising approaches, including new antiviral agents, symptomatic or immunomodulatory drugs, the re-emergence of natural remedies, and vaccines and public health policies toward prevention. Wide-scale prevention through immunization appears to be within reach for respiratory syncytial virus and promising for influenza virus, whereas additional effort is needed in regard to rhinovirus, as well as other respiratory tract viruses.

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          Most cited references130

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          Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies.

          Influenza viruses pose a significant threat to the public and are a burden on global health systems. Each year, influenza vaccines must be rapidly produced to match circulating viruses, a process constrained by dated technology and vulnerable to unexpected strains emerging from humans and animal reservoirs. Here we use knowledge of protein structure to design self-assembling nanoparticles that elicit broader and more potent immunity than traditional influenza vaccines. The viral haemagglutinin was genetically fused to ferritin, a protein that naturally forms nanoparticles composed of 24 identical polypeptides. Haemagglutinin was inserted at the interface of adjacent subunits so that it spontaneously assembled and generated eight trimeric viral spikes on its surface. Immunization with this influenza nanoparticle vaccine elicited haemagglutination inhibition antibody titres more than tenfold higher than those from the licensed inactivated vaccine. Furthermore, it elicited neutralizing antibodies to two highly conserved vulnerable haemagglutinin structures that are targets of universal vaccines: the stem and the receptor binding site on the head. Antibodies elicited by a 1999 haemagglutinin-nanoparticle vaccine neutralized H1N1 viruses from 1934 to 2007 and protected ferrets from an unmatched 2007 H1N1 virus challenge. This structure-based, self-assembling synthetic nanoparticle vaccine improves the potency and breadth of influenza virus immunity, and it provides a foundation for building broader vaccine protection against emerging influenza viruses and other pathogens.
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            Is Open Access

            Viral membrane fusion.

            Membrane fusion is an essential step when enveloped viruses enter cells. Lipid bilayer fusion requires catalysis to overcome a high kinetic barrier; viral fusion proteins are the agents that fulfill this catalytic function. Despite a variety of molecular architectures, these proteins facilitate fusion by essentially the same generic mechanism. Stimulated by a signal associated with arrival at the cell to be infected (e.g., receptor or co-receptor binding, proton binding in an endosome), they undergo a series of conformational changes. A hydrophobic segment (a "fusion loop" or "fusion peptide") engages the target-cell membrane and collapse of the bridging intermediate thus formed draws the two membranes (virus and cell) together. We know of three structural classes for viral fusion proteins. Structures for both pre- and postfusion conformations of illustrate the beginning and end points of a process that can be probed by single-virion measurements of fusion kinetics.
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              Current advances in research and clinical applications of PLGA-based nanotechnology.

              Co-polymer poly(lactic-co-glycolic acid) (PLGA) nanotechnology has been developed for many years and has been approved by the US FDA for the use of drug delivery, diagnostics and other applications of clinical and basic science research, including cardiovascular disease, cancer, vaccine and tissue engineering. This article presents the more recent successes of applying PLGA-based nanotechnologies and tools in these medicine-related applications. It focuses on the possible mechanisms, diagnosis and treatment effects of PLGA preparations and devices. This updated information will benefit to both new and established research scientists and clinical physicians who are interested in the development and application of PLGA nanotechnology as new therapeutic and diagnostic strategies for many diseases.
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                Author and article information

                Contributors
                Journal
                J Allergy Clin Immunol
                J. Allergy Clin. Immunol
                The Journal of Allergy and Clinical Immunology
                American Academy of Allergy, Asthma & Immunology
                0091-6749
                1097-6825
                21 July 2017
                October 2017
                21 July 2017
                : 140
                : 4
                : 921-932
                Affiliations
                [a ]Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, United Kingdom
                [b ]Allergy Department, 2nd Pediatric Clinic, National & Kapodistrian University of Athens, Athens, Greece
                [c ]Department of Nutritional Physiology & Feeding, Agricultural University of Athens, Athens, Greece
                Author notes
                []Corresponding author: Nikolaos G. Papadopoulos, MD, PhD, 2nd Department of Pediatrics, University of Athens, 41 Fidippidou, Goudi, Athens, Greece 11527. ngp@ 123456allergy.gr
                Article
                S0091-6749(17)31113-2
                10.1016/j.jaci.2017.07.001
                7112313
                28739285
                76aa2046-2a08-439d-b224-a67f818212a2
                © 2017 American Academy of Allergy, Asthma & Immunology.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 6 June 2017
                : 11 July 2017
                : 14 July 2017
                Categories
                Article

                Immunology
                influenza,bronchiolitis,common cold,respiratory syncytial virus,rhinovirus,vaccine,monoclonal,antiviral,natural products,public health,copd, chronic obstructive pulmonary disease,ha, hemagglutinin,icam-1, intercellular adhesion molecule 1,ifv, influenza virus,nai, neuraminidase inhibitor,piv, parainfluenza virus,rsv, respiratory syncytial virus,rti, respiratory tract infection,sars, severe acute respiratory syndrome,spm, specialized proresolving lipid mediator,tlr, toll-like receptor,vlp, virus-like particle,vrti, viral respiratory tract infection

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