About: Protease inhibitors targeting coronavirus and filovirus entry

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An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Protease inhibitors targeting coronavirus and filovirus entry
Creator	Pöhlmann, Stefan Lu, Kai Simmons, Graham Carrion, Ricardo Nunneley, Jerritt Zhou, Yanchen Barnard, Dale Agudelo, Juliet Vedantham, Punitha Mckerrow, James Renslo, Adam
Source	Elsevier; Medline; PMC
abstract	Abstract In order to gain entry into cells, diverse viruses, including Ebola virus, SARS-coronavirus and the emerging MERS-coronavirus, depend on activation of their envelope glycoproteins by host cell proteases. The respective enzymes are thus excellent targets for antiviral intervention. In cell culture, activation of Ebola virus, as well as SARS- and MERS-coronavirus can be accomplished by the endosomal cysteine proteases, cathepsin L (CTSL) and cathepsin B (CTSB). In addition, SARS- and MERS-coronavirus can use serine proteases localized at the cell surface, for their activation. However, it is currently unclear which protease(s) facilitate viral spread in the infected host. We report here that the cysteine protease inhibitor K11777, ((2S)-N-[(1E,3S)-1-(benzenesulfonyl)-5-phenylpent-1-en-3-yl]-2-{[(E)-4-methylpiperazine-1-carbonyl]amino}-3-phenylpropanamide) and closely-related vinylsulfones act as broad-spectrum antivirals by targeting cathepsin-mediated cell entry. K11777 is already in advanced stages of development for a number of parasitic diseases, such as Chagas disease, and has proven to be safe and effective in a range of animal models. K11777 inhibition of SARS-CoV and Ebola virus entry was observed in the sub-nanomolar range. In order to assess whether cysteine or serine proteases promote viral spread in the host, we compared the antiviral activity of an optimized K11777-derivative with that of camostat, an inhibitor of TMPRSS2 and related serine proteases. Employing a pathogenic animal model of SARS-CoV infection, we demonstrated that viral spread and pathogenesis of SARS-CoV is driven by serine rather than cysteine proteases and can be effectively prevented by camostat. Camostat has been clinically used to treat chronic pancreatitis, and thus represents an exciting potential therapeutic for respiratory coronavirus infections. Our results indicate that camostat, or similar serine protease inhibitors, might be an effective option for treatment of SARS and potentially MERS, while vinyl sulfone-based inhibitors are excellent lead candidates for Ebola virus therapeutics.
has issue date	2015-04-30(xsd:dateTime)
bibo:doi	10.1016/j.antiviral.2015.01.011
bibo:pmid	25666761
has license	els-covid
sha1sum (hex)	1229bfb6b2481a4afada0a99d545513d3b673c42
schema:url	https://doi.org/10.1016/j.antiviral.2015.01.011
resource representing a document's title	Protease inhibitors targeting coronavirus and filovirus entry
has PubMed Central identifier	PMC4774534
has PubMed identifier	25666761
schema:publication	Antiviral Research
resource representing a document's body	covid:1229bfb6b2481a4afada0a99d545513d3b673c42#body_text
is schema:about of	named entity 'depend' named entity 'cells' covid:arg/1229bfb6b2481a4afada0a99d545513d3b673c42 named entity 'targets' named entity 'viruses' named entity 'antiviral' named entity 'Ebola' named entity 'viruses' named entity 'cysteine protease inhibitor' named entity 'host cell' named entity 'SARS' named entity 'cell culture' named entity 'proteases' named entity 'CTSL' named entity 'cathepsin' named entity 'protease' named entity 'Protease inhibitors' named entity 'coronavirus' named entity 'filovirus' named entity 'Sudan ebolavirus' named entity 'antiviral' named entity 'CTSB' named entity 'endosomal' named entity 'VSV' named entity 'vaccines' named entity 'EBOV' named entity 'human coronaviruses' named entity 'EBOV' named entity 'cell surface' named entity '293T' named entity '293T' named entity 'Lentiviral' named entity 'cysteine protease inhibitor' named entity 'Plasmids' named entity 'nanomolar' named entity 'Kidney' named entity 'cell entry' named entity 'parasites' named entity 'viral entry' named entity 'Ebola' named entity 'TMPRSS2' named entity 'BEBOV' named entity 'tissue culture' named entity 'protease inhibitors' named entity 'VSV' named entity '293T' named entity 'potency' named entity 'filoviruses' named entity 'infectivity' named entity 'flow cytometry' named entity 'protease' named entity 'GFP' named entity 'Toronto' named entity 'serine proteases' named entity 'serine protease inhibitor' named entity 'electrophilic' named entity 'proteases' named entity 'substrate' named entity 'cysteine' named entity 'GFP' named entity 'transmembrane' named entity 'pathogenic viruses' named entity 'cyclopentyl' named entity 'viral entry' named entity 'viral envelope' named entity '12 nM' named entity 'transfection' named entity 'cysteine protease inhibitors' named entity 'cathepsin' named entity '0.45' named entity 'ATCC'

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