Blockers of the sars-cov-2 3a channel identified by targeted drug repurposing

Prabhat Pratap Singh Tomar; Miriam Krugliak; Isaiah T. Arkin

doi:10.3390/v13030532

Blockers of the sars-cov-2 3a channel identified by targeted drug repurposing

Prabhat Pratap Singh Tomar, Miriam Krugliak, Isaiah T. Arkin^*

^*Corresponding author for this work

Department of Biological Chemistry

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

16 Scopus citations

Abstract

The etiological agent of the COVID-19 pandemic is SARS-CoV-2. As a member of the Coronaviridae, the enveloped pathogen has several membrane proteins, of which two, E and 3a, were suggested to function as ion channels. In an effort to increase our treatment options, alongside providing new research tools, we have sought to inhibit the 3a channel by targeted drug repurposing. To that end, using three bacteria-based assays, we screened a library of 2839 approved-for-human-use drugs and identified the following potential channel-blockers: Capreomycin, Pentamidine, Spectinomycin, Kasugamycin, Plerixafor, Flumatinib, Litronesib, Darapladib, Floxuridine and Fludarabine. The stage is now set for examining the activity of these compounds in detailed electrophysiological studies and their impact on the whole virus with appropriate biosafety measures.

Original language	American English
Article number	532
Journal	Viruses
Volume	13
Issue number	3
DOIs	https://doi.org/10.3390/v13030532
State	Published - Mar 2021

Bibliographical note

Funding Information:
This work was supported in part by grants from the Israeli Science Foundation and the Israeli Science Ministry. I.T.A. is the Arthur Lejwa Professor of Structural Biochemistry at the Hebrew University of Jerusalem.

Funding Information:
Funding: This work was supported in part by grants from the Israeli Science Foundation and the Israeli Science Ministry. I.T.A. is the Arthur Lejwa Professor of Structural Biochemistry at the Hebrew University of Jerusalem.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

Antiviral drugs
Bacterial assays
Channel blockers
Viral channels

UN SDGs

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

Access to Document

10.3390/v13030532

Cite this

@article{fafb86534bd3453cabc751eb83fb0c9c,

title = "Blockers of the sars-cov-2 3a channel identified by targeted drug repurposing",

abstract = "The etiological agent of the COVID-19 pandemic is SARS-CoV-2. As a member of the Coronaviridae, the enveloped pathogen has several membrane proteins, of which two, E and 3a, were suggested to function as ion channels. In an effort to increase our treatment options, alongside providing new research tools, we have sought to inhibit the 3a channel by targeted drug repurposing. To that end, using three bacteria-based assays, we screened a library of 2839 approved-for-human-use drugs and identified the following potential channel-blockers: Capreomycin, Pentamidine, Spectinomycin, Kasugamycin, Plerixafor, Flumatinib, Litronesib, Darapladib, Floxuridine and Fludarabine. The stage is now set for examining the activity of these compounds in detailed electrophysiological studies and their impact on the whole virus with appropriate biosafety measures.",

keywords = "Antiviral drugs, Bacterial assays, Channel blockers, Viral channels",

author = "Tomar, {Prabhat Pratap Singh} and Miriam Krugliak and Arkin, {Isaiah T.}",

note = "Funding Information: This work was supported in part by grants from the Israeli Science Foundation and the Israeli Science Ministry. I.T.A. is the Arthur Lejwa Professor of Structural Biochemistry at the Hebrew University of Jerusalem. Funding Information: Funding: This work was supported in part by grants from the Israeli Science Foundation and the Israeli Science Ministry. I.T.A. is the Arthur Lejwa Professor of Structural Biochemistry at the Hebrew University of Jerusalem. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = mar,

doi = "10.3390/v13030532",

language = "American English",

volume = "13",

journal = "Viruses",

issn = "1999-4915",

publisher = "MDPI Multidisciplinary Digital Publishing Institute",

number = "3",

}

TY - JOUR

T1 - Blockers of the sars-cov-2 3a channel identified by targeted drug repurposing

AU - Tomar, Prabhat Pratap Singh

AU - Krugliak, Miriam

AU - Arkin, Isaiah T.

N1 - Funding Information: This work was supported in part by grants from the Israeli Science Foundation and the Israeli Science Ministry. I.T.A. is the Arthur Lejwa Professor of Structural Biochemistry at the Hebrew University of Jerusalem. Funding Information: Funding: This work was supported in part by grants from the Israeli Science Foundation and the Israeli Science Ministry. I.T.A. is the Arthur Lejwa Professor of Structural Biochemistry at the Hebrew University of Jerusalem. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/3

Y1 - 2021/3

N2 - The etiological agent of the COVID-19 pandemic is SARS-CoV-2. As a member of the Coronaviridae, the enveloped pathogen has several membrane proteins, of which two, E and 3a, were suggested to function as ion channels. In an effort to increase our treatment options, alongside providing new research tools, we have sought to inhibit the 3a channel by targeted drug repurposing. To that end, using three bacteria-based assays, we screened a library of 2839 approved-for-human-use drugs and identified the following potential channel-blockers: Capreomycin, Pentamidine, Spectinomycin, Kasugamycin, Plerixafor, Flumatinib, Litronesib, Darapladib, Floxuridine and Fludarabine. The stage is now set for examining the activity of these compounds in detailed electrophysiological studies and their impact on the whole virus with appropriate biosafety measures.

AB - The etiological agent of the COVID-19 pandemic is SARS-CoV-2. As a member of the Coronaviridae, the enveloped pathogen has several membrane proteins, of which two, E and 3a, were suggested to function as ion channels. In an effort to increase our treatment options, alongside providing new research tools, we have sought to inhibit the 3a channel by targeted drug repurposing. To that end, using three bacteria-based assays, we screened a library of 2839 approved-for-human-use drugs and identified the following potential channel-blockers: Capreomycin, Pentamidine, Spectinomycin, Kasugamycin, Plerixafor, Flumatinib, Litronesib, Darapladib, Floxuridine and Fludarabine. The stage is now set for examining the activity of these compounds in detailed electrophysiological studies and their impact on the whole virus with appropriate biosafety measures.

KW - Antiviral drugs

KW - Bacterial assays

KW - Channel blockers

KW - Viral channels

UR - http://www.scopus.com/inward/record.url?scp=85103919743&partnerID=8YFLogxK

U2 - 10.3390/v13030532

DO - 10.3390/v13030532

M3 - Article

C2 - 33807095

AN - SCOPUS:85103919743

SN - 1999-4915

VL - 13

JO - Viruses

JF - Viruses

IS - 3

M1 - 532

ER -

Blockers of the sars-cov-2 3a channel identified by targeted drug repurposing

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this