Enisamium inhibits sars-cov-2 rna synthesis

Stefano Elli; Denisa Bojkova; Marco Bechtel; Thomas Vial; David Boltz; Miguel Muzzio; Xinjian Peng; Federico Sala; Cesare Cosentino; Andrew Goy; Marco Guerrini; Lutz Müller; Jindrich Cinatl; Victor Margitich; Aartjan J.W. Te Velthuis

doi:10.3390/biomedicines9091254

Enisamium inhibits sars-cov-2 rna synthesis

Stefano Elli, Denisa Bojkova, Marco Bechtel, Thomas Vial, David Boltz, Miguel Muzzio, Xinjian Peng, Federico Sala, Cesare Cosentino, Andrew Goy, Marco Guerrini, Lutz Müller, Jindrich Cinatl, Victor Margitich, Aartjan J.W. Te Velthuis

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Pandemic SARS-CoV-2 causes a mild to severe respiratory disease called coronavirus disease 2019 (COVID-19). While control of the SARS-CoV-2 spread partly depends on vaccine-induced or naturally acquired protective herd immunity, antiviral strategies are still needed to manage COVID-19. Enisamium is an inhibitor of influenza A and B viruses in cell culture and clinically approved in countries of the Commonwealth of Independent States. In vitro, enisamium acts through metabolite VR17-04 and inhibits the activity of the influenza A virus RNA polymerase. Here we show that enisamium can inhibit coronavirus infections in NHBE and Caco-2 cells, and the activity of the SARS-CoV-2 RNA polymerase in vitro. Docking and molecular dynamics simulations provide insight into the mechanism of action and indicate that enisamium metabolite VR17-04 prevents GTP and UTP incorporation. Overall, these results suggest that enisamium is an inhibitor of SARS-CoV-2 RNA synthesis in vitro.

Original language	English (US)
Article number	1254
Journal	Biomedicines
Volume	9
Issue number	9
DOIs	https://doi.org/10.3390/biomedicines9091254
State	Published - Sep 2021
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biochemistry, Genetics and Molecular Biology(all)
Medicine (miscellaneous)

Keywords

Amizon
COVID-19
FAV00A
Molecular dynamics simulation
RNA polymerase
SARS-CoV-2

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10.3390/biomedicines9091254

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title = "Enisamium inhibits sars-cov-2 rna synthesis",

abstract = "Pandemic SARS-CoV-2 causes a mild to severe respiratory disease called coronavirus disease 2019 (COVID-19). While control of the SARS-CoV-2 spread partly depends on vaccine-induced or naturally acquired protective herd immunity, antiviral strategies are still needed to manage COVID-19. Enisamium is an inhibitor of influenza A and B viruses in cell culture and clinically approved in countries of the Commonwealth of Independent States. In vitro, enisamium acts through metabolite VR17-04 and inhibits the activity of the influenza A virus RNA polymerase. Here we show that enisamium can inhibit coronavirus infections in NHBE and Caco-2 cells, and the activity of the SARS-CoV-2 RNA polymerase in vitro. Docking and molecular dynamics simulations provide insight into the mechanism of action and indicate that enisamium metabolite VR17-04 prevents GTP and UTP incorporation. Overall, these results suggest that enisamium is an inhibitor of SARS-CoV-2 RNA synthesis in vitro.",

keywords = "Amizon, COVID-19, FAV00A, Molecular dynamics simulation, RNA polymerase, SARS-CoV-2",

author = "Stefano Elli and Denisa Bojkova and Marco Bechtel and Thomas Vial and David Boltz and Miguel Muzzio and Xinjian Peng and Federico Sala and Cesare Cosentino and Andrew Goy and Marco Guerrini and Lutz M{\"u}ller and Jindrich Cinatl and Victor Margitich and {Te Velthuis}, {Aartjan J.W.}",

note = "Funding Information: Funding: A.J.W.t.V. is supported by joint Wellcome Trust and Royal Society grant 206579/Z/17/Z. T.V. is supported by Dutch organization for Health Research (ZonMw) grant 10430 01 201 0018. Part of this research was funded by Farmak Public Joint Stock Company, Kiev, Ukraine. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = sep,

doi = "10.3390/biomedicines9091254",

language = "English (US)",

volume = "9",

journal = "Biomedicines",

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AU - Elli, Stefano

AU - Bojkova, Denisa

AU - Bechtel, Marco

AU - Vial, Thomas

AU - Boltz, David

AU - Muzzio, Miguel

AU - Peng, Xinjian

AU - Sala, Federico

AU - Cosentino, Cesare

AU - Goy, Andrew

AU - Guerrini, Marco

AU - Müller, Lutz

AU - Cinatl, Jindrich

AU - Margitich, Victor

AU - Te Velthuis, Aartjan J.W.

N1 - Funding Information: Funding: A.J.W.t.V. is supported by joint Wellcome Trust and Royal Society grant 206579/Z/17/Z. T.V. is supported by Dutch organization for Health Research (ZonMw) grant 10430 01 201 0018. Part of this research was funded by Farmak Public Joint Stock Company, Kiev, Ukraine. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/9

Y1 - 2021/9

N2 - Pandemic SARS-CoV-2 causes a mild to severe respiratory disease called coronavirus disease 2019 (COVID-19). While control of the SARS-CoV-2 spread partly depends on vaccine-induced or naturally acquired protective herd immunity, antiviral strategies are still needed to manage COVID-19. Enisamium is an inhibitor of influenza A and B viruses in cell culture and clinically approved in countries of the Commonwealth of Independent States. In vitro, enisamium acts through metabolite VR17-04 and inhibits the activity of the influenza A virus RNA polymerase. Here we show that enisamium can inhibit coronavirus infections in NHBE and Caco-2 cells, and the activity of the SARS-CoV-2 RNA polymerase in vitro. Docking and molecular dynamics simulations provide insight into the mechanism of action and indicate that enisamium metabolite VR17-04 prevents GTP and UTP incorporation. Overall, these results suggest that enisamium is an inhibitor of SARS-CoV-2 RNA synthesis in vitro.

AB - Pandemic SARS-CoV-2 causes a mild to severe respiratory disease called coronavirus disease 2019 (COVID-19). While control of the SARS-CoV-2 spread partly depends on vaccine-induced or naturally acquired protective herd immunity, antiviral strategies are still needed to manage COVID-19. Enisamium is an inhibitor of influenza A and B viruses in cell culture and clinically approved in countries of the Commonwealth of Independent States. In vitro, enisamium acts through metabolite VR17-04 and inhibits the activity of the influenza A virus RNA polymerase. Here we show that enisamium can inhibit coronavirus infections in NHBE and Caco-2 cells, and the activity of the SARS-CoV-2 RNA polymerase in vitro. Docking and molecular dynamics simulations provide insight into the mechanism of action and indicate that enisamium metabolite VR17-04 prevents GTP and UTP incorporation. Overall, these results suggest that enisamium is an inhibitor of SARS-CoV-2 RNA synthesis in vitro.

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KW - COVID-19

KW - FAV00A

KW - Molecular dynamics simulation

KW - RNA polymerase

KW - SARS-CoV-2

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Enisamium inhibits sars-cov-2 rna synthesis

Abstract

All Science Journal Classification (ASJC) codes

Keywords

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