Structural Insight into Paramyxovirus and Pneumovirus Entry Inhibition
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 vi...
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doaj-6ace855d56f14313b673dd36a0afa71f2020-11-25T01:44:36ZengMDPI AGViruses1999-49152020-03-0112334210.3390/v12030342v12030342Structural Insight into Paramyxovirus and Pneumovirus Entry InhibitionMegha Aggarwal0Richard K Plemper1Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USAInstitute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USAParamyxoviruses 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.https://www.mdpi.com/1999-4915/12/3/342respiratory syncytial virusparainfluenzavirusmeasles virusnipah viruspneumovirusparamyxovirusvirus entryantiviral therapeuticentry inhibitor |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Megha Aggarwal Richard K Plemper |
spellingShingle |
Megha Aggarwal Richard K Plemper Structural Insight into Paramyxovirus and Pneumovirus Entry Inhibition Viruses respiratory syncytial virus parainfluenzavirus measles virus nipah virus pneumovirus paramyxovirus virus entry antiviral therapeutic entry inhibitor |
author_facet |
Megha Aggarwal Richard K Plemper |
author_sort |
Megha Aggarwal |
title |
Structural Insight into Paramyxovirus and Pneumovirus Entry Inhibition |
title_short |
Structural Insight into Paramyxovirus and Pneumovirus Entry Inhibition |
title_full |
Structural Insight into Paramyxovirus and Pneumovirus Entry Inhibition |
title_fullStr |
Structural Insight into Paramyxovirus and Pneumovirus Entry Inhibition |
title_full_unstemmed |
Structural Insight into Paramyxovirus and Pneumovirus Entry Inhibition |
title_sort |
structural insight into paramyxovirus and pneumovirus entry inhibition |
publisher |
MDPI AG |
series |
Viruses |
issn |
1999-4915 |
publishDate |
2020-03-01 |
description |
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. |
topic |
respiratory syncytial virus parainfluenzavirus measles virus nipah virus pneumovirus paramyxovirus virus entry antiviral therapeutic entry inhibitor |
url |
https://www.mdpi.com/1999-4915/12/3/342 |
work_keys_str_mv |
AT meghaaggarwal structuralinsightintoparamyxovirusandpneumovirusentryinhibition AT richardkplemper structuralinsightintoparamyxovirusandpneumovirusentryinhibition |
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