About: The anti-HIV Drug Nelfinavir Mesylate (Viracept) is a Potent Inhibitor of Cell Fusion Caused by the SARS-CoV-2 Spike (S) Glycoprotein Warranting further Evaluation as an Antiviral against COVID-19 infections

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About: The anti-HIV Drug Nelfinavir Mesylate (Viracept) is a Potent Inhibitor of Cell Fusion Caused by the SARS-CoV-2 Spike (S) Glycoprotein Warranting further Evaluation as an Antiviral against COVID-19 infections Goto Sponge NotDistinct Permalink

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Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	The anti-HIV Drug Nelfinavir Mesylate (Viracept) is a Potent Inhibitor of Cell Fusion Caused by the SARS-CoV-2 Spike (S) Glycoprotein Warranting further Evaluation as an Antiviral against COVID-19 infections
Creator	Kousoulas, Konstantin Chouljenko1, Vladimir Dahal3, Achyut Jois3, Seetharama Musarrat1, Farhana Nabi1, Rafiq
Source	BioRxiv
abstract	Coronaviruses belong to a group of enveloped, positive-single stranded RNA viruses that are known to cause severe respiratory distress in animals and humans. The current SARS coronavirus-2 (SARS CoV-2) pandemic has caused more than 2,000,000 infections globally and nearly 200,000 deaths. Coronaviruses enter susceptible cells via fusion of the viral envelope with the plasma membrane and/or via fusion of the viral envelope with endosomal membranes after endocytosis of the virus into endosomes. Previous results with SARS and MERS CoV have shown that the Spike (S) glycoprotein is a major determinant of virus infectivity and immunogenicity. Herein, we show that expression of SARS CoV-2 S (S-n) glycoprotein after transient transfection of African green monkey kidney (Vero) cells caused extensive cell fusion in comparison to limited cell fusion caused by the SARS S (S-o) glycoprotein. S-n expression was detected intracellularly and on transfected Vero cell surfaces and caused the formation of very large multinucleated cells (syncytia) by 48 hours post transfection. These results are in agreement with published pathology observations of extensive syncytial formation in lung tissues of COVID-19 patients. This differential S-n versus S-o-mediated cell fusion suggests that SARS-CoV-2 is able to spread from cell-to-cell much more efficiently than SARS effectively avoiding extracellular spaces and neutralizing antibodies. A systematic screening of several drugs for ability to inhibit S-n and S-o cell fusion revealed that the FDA approved HIV-protease inhibitor, nelfinavir mesylate (Viracept) drastically inhibited S-n and S-o-mediated cell fusion in a dose-dependent manner. Complete inhibition of cell fusion was observed at a 10 micromolar concentration. Computational modeling and in silico docking experiments suggested the possibility that nelfinavir may bind inside the S trimer structure, proximal to the S2 amino terminus directly inhibiting S-n and S-o-mediated membrane fusion. Also, it is possible that nelfinavir mesylate acts on cellular processes to inhibit S proteolytic processing. These results warrant further investigations of the potential of nelfinavir mesylate as an antiviral drug, especially at early times after SARS-CoV-2 symptoms appear.
has issue date	2020-04-24(xsd:dateTime)
bibo:doi	10.1101/2020.04.24.060376
has license	biorxiv
sha1sum (hex)	1dae808f9f267204fec9c67d4b72a2b53a548c47
schema:url	https://doi.org/10.1101/2020.04.24.060376
resource representing a document's title	The anti-HIV Drug Nelfinavir Mesylate (Viracept) is a Potent Inhibitor of Cell Fusion Caused by the SARS-CoV-2 Spike (S) Glycoprotein Warranting further Evaluation as an Antiviral against COVID-19 infections
schema:publication	bioRxiv
resource representing a document's body	covid:1dae808f9f267204fec9c67d4b72a2b53a548c47#body_text
is schema:about of	named entity 'group' named entity 'respiratory distress' named entity 'neutralizing antibodies' named entity 'patients' named entity 'humans' named entity 'glycoprotein' named entity 'extensive' named entity 'Computational modeling' named entity 'viruses' named entity 'caused' named entity 'extensive' named entity 'expression' named entity 'stranded' named entity 'warrant' named entity 'Viracept' named entity 'Drug' named entity 'EXPRESSION' named entity 'SARS' named entity 'RESULTS' named entity 'IMMUNOGENICITY' named entity 'POST' named entity 'THESE' named entity 'MEDIATED' named entity 'LIMITED' named entity 'NELFINAVIR' named entity 'CELL FUSION' named entity 'NELFINAVIR MESYLATE' named entity 'HUMANS' named entity 'CORONAVIRUSES' named entity '28S' named entity 'ANIMALS' named entity 'NEARLY' named entity 'caused' named entity 'observed' named entity 'endocytosis' named entity 'post' named entity 'observations' named entity 'inhibitor' named entity 'current' named entity 'nelfinavir mesylate' named entity 'nelfinavir mesylate' named entity 'SARS-CoV-2' named entity 'surfaces' named entity 'transfection' named entity 'Antiviral' named entity 'Vero cell' named entity 'COVID' named entity 'viral envelope' named entity 'multinucleated cells' named entity 'FDA' named entity 'syncytial' named entity 'SARS' named entity 'nelfinavir mesylate' named entity 'endosomes' named entity 'transfection' named entity 'glycoprotein' named entity 'cell fusion' named entity 'lung' named entity 'syncytia' named entity 'virus' named entity 'SARS CoV' named entity 'Nelfinavir Mesylate' named entity 'immunohistochemistry' named entity 'amino termini' named entity 'S-n' named entity 'DMEM' named entity 'cellular processes' named entity 'protein' named entity 'N-MYC' named entity 'apoptosis' named entity 'fluorescent microscopy' named entity 'transfection' named entity 'DMSO' named entity 'plasmid DNA' named entity 'unfolded protein response' named entity 'African green monkey kidney cells' named entity 'PDB' named entity 'HR2' named entity 'S-n'

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