Middle East Respiratory Syndrome Coronavirus Infection Mediated by the Transmembrane Serine Protease TMPRSS2
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It is suggested that a single treatment with camostat is sufficient to block MERS-CoV entry into a well-differentiated lung-derived cell line and cathepsin L in the endosome.Citations
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COVID-19: Drug targets and potential treatments.
Carmen Gil,Tiziana Ginex,Inés Maestro,Vanesa Nozal,Lucía Barrado-Gil,Miguel Ángel Cuesta-Geijo,Jesús Urquiza,David Ramírez,Covadonga Alonso,Nuria E. Campillo,Ana Martínez +10 more
TL;DR: An overview of the main targets from a structural point of view, together with reported therapeutic compounds with activity against SARS-CoV-2 and/or other CoVs are provided.
Journal ArticleDOI
Identification of Nafamostat as a Potent Inhibitor of Middle East Respiratory Syndrome Coronavirus S Protein-Mediated Membrane Fusion Using the Split-Protein-Based Cell-Cell Fusion Assay
Mizuki Yamamoto,Shutoku Matsuyama,Xiao Li,Makoto Takeda,Yasushi Kawaguchi,Jun-ichiro Inoue,Zene Matsuda,Zene Matsuda +7 more
TL;DR: A cell-based fusion assay for S in a TMPRSS2-dependent manner using cell lines expressing Renilla luciferase (RL)-based split reporter proteins has the potential to facilitate the discovery of new inhibitors of membrane fusion of MERS-CoV as well as other viruses that rely on the activity of TMPR SS2.
Journal ArticleDOI
Proteolytic processing of Middle East respiratory syndrome coronavirus spikes expands virus tropism
Jung-Eun Park,Kun Li,Arlene Barlan,Anthony R. Fehr,Stanley Perlman,Paul B. McCray,Tom Gallagher +6 more
TL;DR: By sensitizing viruses to receptor-induced conformational changes, the first S cleavages expand virus tropism to cell types that are relevant to lung infection, and therefore may be significant determinants of MERS-CoV virulence.
Journal ArticleDOI
Genetic Screens Identify Host Factors for SARS-CoV-2 and Common Cold Coronaviruses.
Ruofan Wang,Camille R. Simoneau,Jessie Kulsuptrakul,Mehdi Bouhaddou,Katherine A. Travisano,Jennifer M. Hayashi,Jennifer M. Hayashi,Jared Carlson-Stevermer,James Zengel,Christopher M. Richards,Parinaz Fozouni,Jennifer Oki,Lauren Rodriguez,Bastian Joehnk,Keith Walcott,Kevin Holden,Anita Sil,Jan E. Carette,Nevan J. Krogan,Melanie Ott,Melanie Ott,Andreas S. Puschnik +21 more
TL;DR: Pharmacological inhibition of phosphatidylinositol kinases and cholesterol homeostasis reduced replication of all three coronaviruses and offer important insights for the understanding of the coronavirus life cycle and the development of host-directed therapies.
Journal ArticleDOI
Syncytia formation by SARS-CoV-2-infected cells.
Julian Buchrieser,Julian Buchrieser,Jérémy Dufloo,Jérémy Dufloo,Jérémy Dufloo,Mathieu Hubert,Mathieu Hubert,Blandine Monel,Blandine Monel,Delphine Planas,Delphine Planas,Maaran Michael Rajah,Maaran Michael Rajah,Maaran Michael Rajah,Cyril Planchais,Françoise Porrot,Françoise Porrot,Florence Guivel-Benhassine,Florence Guivel-Benhassine,Sylvie van der Werf,Sylvie van der Werf,Nicoletta Casartelli,Nicoletta Casartelli,Hugo Mouquet,Timothée Bruel,Timothée Bruel,Olivier Schwartz,Olivier Schwartz +27 more
TL;DR: The results show that SARS‐CoV‐2 pathological effects are modulated by cellular proteins that either inhibit or facilitate syncytia formation.
References
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Journal ArticleDOI
Isolation of a Novel Coronavirus from a Man with Pneumonia in Saudi Arabia
Ali Moh Zaki,Sander van Boheemen,Theo M. Bestebroer,Albert D. M. E. Osterhaus,Ron A. M. Fouchier +4 more
TL;DR: The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.
Journal ArticleDOI
Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC
V. Stalin Raj,Huihui Mou,Saskia L. Smits,Dick H. W. Dekkers,Marcel A. Müller,Ronald Dijkman,Doreen Muth,Jeroen Demmers,Ali Moh Zaki,Ron A. M. Fouchier,Volker Thiel,Volker Thiel,Christian Drosten,Peter J. M. Rottier,Albert D. M. E. Osterhaus,Berend Jan Bosch,Bart L. Haagmans +16 more
TL;DR: Dipeptidyl peptidase 4 (DPP4; also known as CD26) is identified as a functional receptor for hCoV-EMC and will contribute critically to the understanding of the pathogenesis and epidemiology of this emerging human coronavirus, and may facilitate the development of intervention strategies.
Journal ArticleDOI
Middle East respiratory syndrome coronavirus (MERS-CoV): announcement of the Coronavirus Study Group.
Raoul J. de Groot,Susan C. Baker,Ralph S. Baric,Caroline Brown,Christian Drosten,Luis Enjuanes,Ron A. M. Fouchier,Monica Galiano,Alexander E. Gorbalenya,Ziad A. Memish,Stanley Perlman,Leo L.M. Poon,Eric J. Snijder,Gwen Stephens,Patrick C. Y. Woo,Ali Moh Zaki,Maria Zambon,John Ziebuhr +17 more
TL;DR: During the summer of 2012, in Jeddah, Saudi Arabia, a hitherto unknown coronavirus was isolated from the sputum of a patient with acute pneumonia and renal failure and was provisionally called human coronav virus Erasmus Medical Center (EMC).
Journal ArticleDOI
Efficient Activation of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein by the Transmembrane Protease TMPRSS2
TL;DR: This is the first report of TMPRSS2 being required in the target cell for activation of a viral fusion protein but not for the S protein synthesized in and transported to the surface of cells.
Journal ArticleDOI
A Transmembrane Serine Protease Is Linked to the Severe Acute Respiratory Syndrome Coronavirus Receptor and Activates Virus Entry
Ana Shulla,Taylor Heald-Sargent,Gitanjali Subramanya,Jincun Zhao,Stanley Perlman,Tom Gallagher +5 more
TL;DR: Findings indicate that a cell surface complex comprising a primary receptor and a separate endoprotease operates as a portal for activation of SARS-CoV cell entry.