Repurposing dyphylline as a pan-coronavirus antiviral therapy

Yining Wang; Sajjan Rajpoot; Pengfei Li; Marla Lavrijsen; Zhongren Ma; Nik Hirani; Uzma Saqib; Qiuwei Pan; Mirza S Baig

doi:10.4155/fmc-2021-0311

Repurposing dyphylline as a pan-coronavirus antiviral therapy

Yining Wang, Sajjan Rajpoot, Pengfei Li, Marla Lavrijsen, Zhongren Ma, Nik Hirani, Uzma Saqib, Qiuwei Pan^*, Mirza S Baig^*

^*Corresponding author for this work

Gastroenterology & Hepatology

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

7 Citations (Scopus)

43 Downloads (Pure)

Abstract

Background: In the last two decades, the world has witnessed the emergence of zoonotic corona viruses (CoVs), which cause mild to severe respiratory diseases in humans. Human coronaviruses (HCoVs), mainly from the alpha-CoV and beta-CoV genera, have evolved to be highly pathogenic, such as SARS-CoV-2 causing the COVID-19 pandemic. These coronaviruses carry functional enzymes necessary for the virus life cycle, which represent attractive antiviral targets. Methods & Results: We aimed to therapeutically target the main protease (Mpro) of HCoV-NL63 and HCoV-229E (from alpha-CoV genus) and HCoV-OC43 and SARS-CoV-2 (from beta-CoV genus). Through virtual screening, we identified an FDA-approved drug dyphylline, a xanthine derivate, that binds to the catalytic dyad residues; histidine and cystine of the Mpro structures. Importantly, dyphylline dose-dependently inhibited the viral replication in cell culture models infected with the viruses. Conclusion: Our findings support the repurposing of dyphylline as a pan-coronavirus antiviral agent.

Original language	English
Pages (from-to)	685-699
Number of pages	15
Journal	Future Medicinal Chemistry
Volume	14
Issue number	10
DOIs	https://doi.org/10.4155/fmc-2021-0311
Publication status	Published - May 2022

Bibliographical note

Funding Information:
The authors also gratefully acknowledge the Indian Institute of Technology Indore (IITI) (MHRD) for providing facilities and other support. This work was supported by Cumulative Professional Development Allowance (CPDA) from the Indian Institute of Technology Indore (IITI) to MSB.

Publisher Copyright:
© 2022 Newlands Press.

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Repurposing dyphylline as a pan-coronavirus antiviral therapyFinal published version, 11.6 MBLicence: CC BY

Cite this

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title = "Repurposing dyphylline as a pan-coronavirus antiviral therapy",

abstract = "Background: In the last two decades, the world has witnessed the emergence of zoonotic corona viruses (CoVs), which cause mild to severe respiratory diseases in humans. Human coronaviruses (HCoVs), mainly from the alpha-CoV and beta-CoV genera, have evolved to be highly pathogenic, such as SARS-CoV-2 causing the COVID-19 pandemic. These coronaviruses carry functional enzymes necessary for the virus life cycle, which represent attractive antiviral targets. Methods & Results: We aimed to therapeutically target the main protease (Mpro) of HCoV-NL63 and HCoV-229E (from alpha-CoV genus) and HCoV-OC43 and SARS-CoV-2 (from beta-CoV genus). Through virtual screening, we identified an FDA-approved drug dyphylline, a xanthine derivate, that binds to the catalytic dyad residues; histidine and cystine of the Mpro structures. Importantly, dyphylline dose-dependently inhibited the viral replication in cell culture models infected with the viruses. Conclusion: Our findings support the repurposing of dyphylline as a pan-coronavirus antiviral agent.",

author = "Yining Wang and Sajjan Rajpoot and Pengfei Li and Marla Lavrijsen and Zhongren Ma and Nik Hirani and Uzma Saqib and Qiuwei Pan and Baig, {Mirza S}",

note = "Funding Information: The authors also gratefully acknowledge the Indian Institute of Technology Indore (IITI) (MHRD) for providing facilities and other support. This work was supported by Cumulative Professional Development Allowance (CPDA) from the Indian Institute of Technology Indore (IITI) to MSB. Publisher Copyright: {\textcopyright} 2022 Newlands Press.",

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doi = "10.4155/fmc-2021-0311",

language = "English",

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pages = "685--699",

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AU - Wang, Yining

AU - Rajpoot, Sajjan

AU - Li, Pengfei

AU - Lavrijsen, Marla

AU - Ma, Zhongren

AU - Hirani, Nik

AU - Saqib, Uzma

AU - Pan, Qiuwei

AU - Baig, Mirza S

N1 - Funding Information: The authors also gratefully acknowledge the Indian Institute of Technology Indore (IITI) (MHRD) for providing facilities and other support. This work was supported by Cumulative Professional Development Allowance (CPDA) from the Indian Institute of Technology Indore (IITI) to MSB. Publisher Copyright: © 2022 Newlands Press.

PY - 2022/5

Y1 - 2022/5

N2 - Background: In the last two decades, the world has witnessed the emergence of zoonotic corona viruses (CoVs), which cause mild to severe respiratory diseases in humans. Human coronaviruses (HCoVs), mainly from the alpha-CoV and beta-CoV genera, have evolved to be highly pathogenic, such as SARS-CoV-2 causing the COVID-19 pandemic. These coronaviruses carry functional enzymes necessary for the virus life cycle, which represent attractive antiviral targets. Methods & Results: We aimed to therapeutically target the main protease (Mpro) of HCoV-NL63 and HCoV-229E (from alpha-CoV genus) and HCoV-OC43 and SARS-CoV-2 (from beta-CoV genus). Through virtual screening, we identified an FDA-approved drug dyphylline, a xanthine derivate, that binds to the catalytic dyad residues; histidine and cystine of the Mpro structures. Importantly, dyphylline dose-dependently inhibited the viral replication in cell culture models infected with the viruses. Conclusion: Our findings support the repurposing of dyphylline as a pan-coronavirus antiviral agent.

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Repurposing dyphylline as a pan-coronavirus antiviral therapy

Abstract

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