Acriflavine, a clinically approved drug, inhibits SARS-CoV-2 and other betacoronaviruses

Valeria Napolitano; Agnieszka Dabrowska; Kenji Schorpp; André Mourão; Emilia Barreto-Duran; Malgorzata Benedyk; Pawel Botwina; Stefanie Brandner; Mark Bostock; Yuliya Chykunova; Anna Czarna; Grzegorz Dubin; Tony Fröhlich; Michael Hölscher; Malwina Jedrysik; Alex Matsuda; Katarzyna Owczarek; Magdalena Pachota; Oliver Plettenburg; Jan Potempa; Ina Rothenaigner; Florian Schlauderer; Klaudia Slysz; Artur Szczepanski; Kristin Greve-Isdahl Mohn; Bjorn Blomberg; Michael Sattler; Kamyar Hadian; Grzegorz Maria Popowicz; Krzysztof Pyrc

doi:10.1016/j.chembiol.2021.11.006

Acriflavine, a clinically approved drug, inhibits SARS-CoV-2 and other betacoronaviruses

Valeria Napolitano, Agnieszka Dabrowska, Kenji Schorpp, André Mourão, Emilia Barreto-Duran, Malgorzata Benedyk, Pawel Botwina, Stefanie Brandner, Mark Bostock, Yuliya Chykunova, Anna Czarna, Grzegorz Dubin, Tony Fröhlich, Michael Hölscher, Malwina Jedrysik, Alex Matsuda, Katarzyna Owczarek, Magdalena Pachota, Oliver Plettenburg, Jan PotempaIna Rothenaigner, Florian Schlauderer, Klaudia Slysz, Artur Szczepanski, Kristin Greve-Isdahl Mohn, Bjorn Blomberg, Michael Sattler, Kamyar Hadian, Grzegorz Maria Popowicz, Krzysztof Pyrc

Chair of Biomolecular NMR-Spectroscopy

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

43 Scopus citations

Abstract

The COVID-19 pandemic caused by SARS-CoV-2 has been socially and economically devastating. Despite an unprecedented research effort and available vaccines, effective therapeutics are still missing to limit severe disease and mortality. Using high-throughput screening, we identify acriflavine (ACF) as a potent papain-like protease (PL^pro) inhibitor. NMR titrations and a co-crystal structure confirm that acriflavine blocks the PL^pro catalytic pocket in an unexpected binding mode. We show that the drug inhibits viral replication at nanomolar concentration in cellular models, in vivo in mice and ex vivo in human airway epithelia, with broad range activity against SARS-CoV-2 and other betacoronaviruses. Considering that acriflavine is an inexpensive drug approved in some countries, it may be immediately tested in clinical trials and play an important role during the current pandemic and future outbreaks.

Original language	English
Pages (from-to)	774-784.e8
Journal	Cell Chemical Biology
Volume	29
Issue number	5
DOIs	https://doi.org/10.1016/j.chembiol.2021.11.006
State	Published - 19 May 2022

Keywords

COVID-19
PL
SARS-CoV-2
acriflavine
coronavirus
drug repurposing
protease
protease inhibitor
structural biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.chembiol.2021.11.006

Cite this

Napolitano, V., Dabrowska, A., Schorpp, K., Mourão, A., Barreto-Duran, E., Benedyk, M., Botwina, P., Brandner, S., Bostock, M., Chykunova, Y., Czarna, A., Dubin, G., Fröhlich, T., Hölscher, M., Jedrysik, M., Matsuda, A., Owczarek, K., Pachota, M., Plettenburg, O., ... Pyrc, K. (2022). Acriflavine, a clinically approved drug, inhibits SARS-CoV-2 and other betacoronaviruses. Cell Chemical Biology, 29(5), 774-784.e8. https://doi.org/10.1016/j.chembiol.2021.11.006

@article{b9450a0111fa40b189a585449bd4463d,

title = "Acriflavine, a clinically approved drug, inhibits SARS-CoV-2 and other betacoronaviruses",

abstract = "The COVID-19 pandemic caused by SARS-CoV-2 has been socially and economically devastating. Despite an unprecedented research effort and available vaccines, effective therapeutics are still missing to limit severe disease and mortality. Using high-throughput screening, we identify acriflavine (ACF) as a potent papain-like protease (PLpro) inhibitor. NMR titrations and a co-crystal structure confirm that acriflavine blocks the PLpro catalytic pocket in an unexpected binding mode. We show that the drug inhibits viral replication at nanomolar concentration in cellular models, in vivo in mice and ex vivo in human airway epithelia, with broad range activity against SARS-CoV-2 and other betacoronaviruses. Considering that acriflavine is an inexpensive drug approved in some countries, it may be immediately tested in clinical trials and play an important role during the current pandemic and future outbreaks.",

keywords = "COVID-19, PL, SARS-CoV-2, acriflavine, coronavirus, drug repurposing, protease, protease inhibitor, structural biology",

author = "Valeria Napolitano and Agnieszka Dabrowska and Kenji Schorpp and Andr{\'e} Mour{\~a}o and Emilia Barreto-Duran and Malgorzata Benedyk and Pawel Botwina and Stefanie Brandner and Mark Bostock and Yuliya Chykunova and Anna Czarna and Grzegorz Dubin and Tony Fr{\"o}hlich and Michael H{\"o}lscher and Malwina Jedrysik and Alex Matsuda and Katarzyna Owczarek and Magdalena Pachota and Oliver Plettenburg and Jan Potempa and Ina Rothenaigner and Florian Schlauderer and Klaudia Slysz and Artur Szczepanski and {Greve-Isdahl Mohn}, Kristin and Bjorn Blomberg and Michael Sattler and Kamyar Hadian and Popowicz, {Grzegorz Maria} and Krzysztof Pyrc",

note = "Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2022",

month = may,

day = "19",

doi = "10.1016/j.chembiol.2021.11.006",

language = "English",

volume = "29",

pages = "774--784.e8",

journal = "Cell Chemical Biology",

issn = "2451-9456",

publisher = "Elsevier Ltd.",

number = "5",

}

Napolitano, V, Dabrowska, A, Schorpp, K, Mourão, A, Barreto-Duran, E, Benedyk, M, Botwina, P, Brandner, S, Bostock, M, Chykunova, Y, Czarna, A, Dubin, G, Fröhlich, T, Hölscher, M, Jedrysik, M, Matsuda, A, Owczarek, K, Pachota, M, Plettenburg, O, Potempa, J, Rothenaigner, I, Schlauderer, F, Slysz, K, Szczepanski, A, Greve-Isdahl Mohn, K, Blomberg, B, Sattler, M, Hadian, K, Popowicz, GM & Pyrc, K 2022, 'Acriflavine, a clinically approved drug, inhibits SARS-CoV-2 and other betacoronaviruses', Cell Chemical Biology, vol. 29, no. 5, pp. 774-784.e8. https://doi.org/10.1016/j.chembiol.2021.11.006

TY - JOUR

T1 - Acriflavine, a clinically approved drug, inhibits SARS-CoV-2 and other betacoronaviruses

AU - Napolitano, Valeria

AU - Dabrowska, Agnieszka

AU - Schorpp, Kenji

AU - Mourão, André

AU - Barreto-Duran, Emilia

AU - Benedyk, Malgorzata

AU - Botwina, Pawel

AU - Brandner, Stefanie

AU - Bostock, Mark

AU - Chykunova, Yuliya

AU - Czarna, Anna

AU - Dubin, Grzegorz

AU - Fröhlich, Tony

AU - Hölscher, Michael

AU - Jedrysik, Malwina

AU - Matsuda, Alex

AU - Owczarek, Katarzyna

AU - Pachota, Magdalena

AU - Plettenburg, Oliver

AU - Potempa, Jan

AU - Rothenaigner, Ina

AU - Schlauderer, Florian

AU - Slysz, Klaudia

AU - Szczepanski, Artur

AU - Greve-Isdahl Mohn, Kristin

AU - Blomberg, Bjorn

AU - Sattler, Michael

AU - Hadian, Kamyar

AU - Popowicz, Grzegorz Maria

AU - Pyrc, Krzysztof

PY - 2022/5/19

Y1 - 2022/5/19

N2 - The COVID-19 pandemic caused by SARS-CoV-2 has been socially and economically devastating. Despite an unprecedented research effort and available vaccines, effective therapeutics are still missing to limit severe disease and mortality. Using high-throughput screening, we identify acriflavine (ACF) as a potent papain-like protease (PLpro) inhibitor. NMR titrations and a co-crystal structure confirm that acriflavine blocks the PLpro catalytic pocket in an unexpected binding mode. We show that the drug inhibits viral replication at nanomolar concentration in cellular models, in vivo in mice and ex vivo in human airway epithelia, with broad range activity against SARS-CoV-2 and other betacoronaviruses. Considering that acriflavine is an inexpensive drug approved in some countries, it may be immediately tested in clinical trials and play an important role during the current pandemic and future outbreaks.

AB - The COVID-19 pandemic caused by SARS-CoV-2 has been socially and economically devastating. Despite an unprecedented research effort and available vaccines, effective therapeutics are still missing to limit severe disease and mortality. Using high-throughput screening, we identify acriflavine (ACF) as a potent papain-like protease (PLpro) inhibitor. NMR titrations and a co-crystal structure confirm that acriflavine blocks the PLpro catalytic pocket in an unexpected binding mode. We show that the drug inhibits viral replication at nanomolar concentration in cellular models, in vivo in mice and ex vivo in human airway epithelia, with broad range activity against SARS-CoV-2 and other betacoronaviruses. Considering that acriflavine is an inexpensive drug approved in some countries, it may be immediately tested in clinical trials and play an important role during the current pandemic and future outbreaks.

KW - COVID-19

KW - PL

KW - SARS-CoV-2

KW - acriflavine

KW - coronavirus

KW - drug repurposing

KW - protease

KW - protease inhibitor

KW - structural biology

UR - http://www.scopus.com/inward/record.url?scp=85122625842&partnerID=8YFLogxK

U2 - 10.1016/j.chembiol.2021.11.006

DO - 10.1016/j.chembiol.2021.11.006

M3 - Article

C2 - 35021060

AN - SCOPUS:85122625842

SN - 2451-9456

VL - 29

SP - 774-784.e8

JO - Cell Chemical Biology

JF - Cell Chemical Biology

IS - 5

ER -

Acriflavine, a clinically approved drug, inhibits SARS-CoV-2 and other betacoronaviruses

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this