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Structural Insight into Paramyxovirus and Pneumovirus Entry Inhibition

Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA
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Viruses 2020, 12(3), 342; https://doi.org/10.3390/v12030342
Received: 7 March 2020 / Revised: 17 March 2020 / Accepted: 18 March 2020 / Published: 20 March 2020
(This article belongs to the Special Issue Mechanisms of Viral Fusion and Applications in Antivirals)
Paramyxoviruses and pneumoviruses infect cells through fusion (F) protein-mediated merger of the viral envelope with target membranes. Members of these families include a range of major human and animal pathogens, such as respiratory syncytial virus (RSV), measles virus (MeV), human parainfluenza viruses (HPIVs), and highly pathogenic Nipah virus (NiV). High-resolution F protein structures in both the metastable pre- and the postfusion conformation have been solved for several members of the families and a number of F-targeting entry inhibitors have progressed to advanced development or clinical testing. However, small-molecule RSV entry inhibitors have overall disappointed in clinical trials and viral resistance developed rapidly in experimental settings and patients, raising the question of whether the available structural information may provide a path to counteract viral escape through proactive inhibitor engineering. This article will summarize current mechanistic insight into F-mediated membrane fusion and examine the contribution of structural information to the development of small-molecule F inhibitors. Implications are outlined for future drug target selection and rational drug engineering strategies. View Full-Text
Keywords: Respiratory syncytial virus; parainfluenzavirus; measles virus; nipah virus; pneumovirus; paramyxovirus; virus entry; antiviral therapeutic; entry inhibitor Respiratory syncytial virus; parainfluenzavirus; measles virus; nipah virus; pneumovirus; paramyxovirus; virus entry; antiviral therapeutic; entry inhibitor
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MDPI and ACS Style

Aggarwal, M.; Plemper, R.K. Structural Insight into Paramyxovirus and Pneumovirus Entry Inhibition. Viruses 2020, 12, 342. https://doi.org/10.3390/v12030342

AMA Style

Aggarwal M, Plemper RK. Structural Insight into Paramyxovirus and Pneumovirus Entry Inhibition. Viruses. 2020; 12(3):342. https://doi.org/10.3390/v12030342

Chicago/Turabian Style

Aggarwal, Megha; Plemper, Richard K 2020. "Structural Insight into Paramyxovirus and Pneumovirus Entry Inhibition" Viruses 12, no. 3: 342. https://doi.org/10.3390/v12030342

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