Antiviral Research, volume 209, pages 105508

5-(Perylen-3-ylethynyl)uracil as an antiviral scaffold: Potent suppression of enveloped virus reproduction by 3-methyl derivatives in vitro

Chistov Alexey A. ¹

Чумаков С. П. ¹

Mikhnovets Igor E. ^{1, 2}

Nikitin Timofei D ^{1, 2}

Slesarchuk Nikita A. ¹

Uvarova Victoria I ³

Rubekina Anna A ⁴

Nikolaeva Yulia ⁵

Radchenko Eugene V. ²

Khvatov Evgeny V. ³

Orlov Alexey A. ^{2, 3, 6}

Frolenko Vasilisa S. ^{3, 7}

Sukhorukov Maksim V. ^{2, 3}

Kolpakova Ekaterina S ³

Shustova Elena Yu. ³

Galochkina Anastasiya V. ⁵

Streshnev Philipp P. ¹

Osipov Eugene M. ⁸

Sapozhnikova Ksenia A. ¹

Moiseenko A V ⁹

Brylev V. A.

Proskurin Gleb V

Dokukin Yuri S.

Kutyakov Sergey V

Aralov Andrey V ⁹

Korshun Vladimir A.

Strelkov Sergei V.

Palyulin Vladimir A.

Ishmukhametov Aydar A

Shirshin Evgeny ³

Osolodkin Dmitry I.

Shtro Anna A ⁴

Kozlovskaya Liubov I.

Alferova Vera A

Ustinov A.V.

Hide authors affiliations Show authors affiliations: 9 affiliations

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997, Russia |

Department of Chemistry, Lomonosov Moscow State University, Moscow, 119991, Russia |

FSASI “Chumakov FSC R&D IBP RAS” (Institute of Poliomyelitis), Moscow, 108819, Russia |

⁴

Department of Physics, Lomonosov Moscow State University, Moscow, 119991, Russia |

⁵

Smorodintsev Research Institute of Influenza, St. Petersburg, 197376, Russia |

⁶

Skolkovo Institute of Science and Technology, 143026, Moscow Region, Russia |

⁷

Institute of Translational Medicine and Biotechnology, Sechenov Moscow State Medical University, Moscow, 119991, Russia |

⁸

Laboratory for Biocrystallography, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, 3000, Leuven, Belgium |

⁹

Department of Biology, Moscow State University, Moscow, 119991, Russia |

Publication type: Journal Article

Publication date: 2023-01-01

Elsevier

Journal: Antiviral Research

Quartile SCImago

Quartile WOS

Impact factor: 7.6

ISSN: 01663542, 18729096

DOI: 10.1016/j.antiviral.2022.105508

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Pharmacology

Virology

Abstract

Amphipathic nucleoside and non-nucleoside derivatives of pentacyclic aromatic hydrocarbon perylene are known as potent non-cytotoxic broad-spectrum antivirals. Here we report 3-methyl-5-(perylen-3-ylethynyl)-uracil-1-acetic acid and its amides, a new series of compounds based on a 5-(perylen-3-ylethynyl)-uracil scaffold. The compounds demonstrate pronounced in vitro activity against arthropod-borne viruses, namely tick-borne encephalitis virus (TBEV) and yellow fever virus (YFV), in plaque reduction assays with EC50 values below 1.9 and 1.3 nM, respectively, and Chikungunya virus (CHIKV) in cytopathic effect inhibition test with EC50 values below 3.2 μM. The compounds are active against respiratory viruses as well: severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in cytopathic effect inhibition test and influenza A virus (IAV) in virus titer reduction experiments are inhibited - EC50 values below 51 nM and 2.2 μM, respectively. The activity stems from the presence of a hydrophobic perylene core, and all of the synthesized compounds exhibit comparable 1O2 generation rates. Nonetheless, activity can vary by orders of magnitude depending on the hydrophilic part of the molecule, suggesting a complex mode of action. A time-of-addition experiment and fluorescent imaging indicate that the compounds inhibit viral fusion in a dose-dependent manner. The localization of the compound in the lipid bilayers and visible damage to the viral envelope suggest the membrane as the primary target. Dramatic reduction of antiviral activity with limited irradiation or under treatment with antioxidants further cements the idea of photoinduced ROS-mediated viral envelope damage being the mode of antiviral action.

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Citations by journals

	1
Archiv der Pharmazie	Archiv der Pharmazie, 1, 12.5% Archiv der Pharmazie 1 publication, 12.5%
Virus Research	Virus Research, 1, 12.5% Virus Research 1 publication, 12.5%
Current Issues in Molecular Biology	Current Issues in Molecular Biology, 1, 12.5% Current Issues in Molecular Biology 1 publication, 12.5%
Molecules	Molecules, 1, 12.5% Molecules 1 publication, 12.5%
International Journal of Molecular Sciences	International Journal of Molecular Sciences, 1, 12.5% International Journal of Molecular Sciences 1 publication, 12.5%
Antiviral Research	Antiviral Research, 1, 12.5% Antiviral Research 1 publication, 12.5%
Bioorganic and Medicinal Chemistry	Bioorganic and Medicinal Chemistry, 1, 12.5% Bioorganic and Medicinal Chemistry 1 publication, 12.5%
Antibiotics	Antibiotics, 1, 12.5% Antibiotics 1 publication, 12.5%
	1

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Multidisciplinary Digital Publishing Institute (MDPI)	Multidisciplinary Digital Publishing Institute (MDPI), 4, 50% Multidisciplinary Digital Publishing Institute (MDPI) 4 publications, 50%
Elsevier	Elsevier, 3, 37.5% Elsevier 3 publications, 37.5%
Wiley	Wiley, 1, 12.5% Wiley 1 publication, 12.5%
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Chistov A. A. et al. 5-(Perylen-3-ylethynyl)uracil as an antiviral scaffold: Potent suppression of enveloped virus reproduction by 3-methyl derivatives in vitro // Antiviral Research. 2023. Vol. 209. p. 105508.

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Chistov A. A., Чумаков С. П., Mikhnovets I. E., Nikitin T. D., Slesarchuk N. A., Uvarova V. I., Rubekina A. A., Nikolaeva Y., Radchenko E. V., Khvatov E. V., Orlov A. A., Frolenko V. S., Sukhorukov M. V., Kolpakova E. S., Shustova E. Y., Galochkina A. V., Streshnev P. P., Osipov E. M., Sapozhnikova K. A., Moiseenko A. V., Brylev V. A., Proskurin G. V., Dokukin Y. S., Kutyakov S. V., Aralov A., Korshun V. A., Strelkov S. V., Palyulin V. A., Ishmukhametov A. A., Shirshin E., Osolodkin D. I., Shtro A. A., Kozlovskaya L. I., Alferova V. A., Ustinov A. 5-(Perylen-3-ylethynyl)uracil as an antiviral scaffold: Potent suppression of enveloped virus reproduction by 3-methyl derivatives in vitro // Antiviral Research. 2023. Vol. 209. p. 105508.

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RIS Copy

TY - JOUR

DO - 10.1016/j.antiviral.2022.105508

UR - https://doi.org/10.1016%2Fj.antiviral.2022.105508

TI - 5-(Perylen-3-ylethynyl)uracil as an antiviral scaffold: Potent suppression of enveloped virus reproduction by 3-methyl derivatives in vitro

T2 - Antiviral Research

AU - Chistov, Alexey A.

AU - Чумаков, С. П.

AU - Mikhnovets, Igor E.

AU - Nikitin, Timofei D

AU - Slesarchuk, Nikita A.

AU - Uvarova, Victoria I

AU - Rubekina, Anna A

AU - Nikolaeva, Yulia

AU - Radchenko, Eugene V.

AU - Khvatov, Evgeny V.

AU - Orlov, Alexey A.

AU - Frolenko, Vasilisa S.

AU - Sukhorukov, Maksim V.

AU - Kolpakova, Ekaterina S

AU - Shustova, Elena Yu.

AU - Galochkina, Anastasiya V.

AU - Streshnev, Philipp P.

AU - Osipov, Eugene M.

AU - Sapozhnikova, Ksenia A.

AU - Moiseenko, A V

AU - Brylev, V. A.

AU - Proskurin, Gleb V

AU - Dokukin, Yuri S.

AU - Kutyakov, Sergey V

AU - Aralov, Andrey V

AU - Korshun, Vladimir A.

AU - Strelkov, Sergei V.

AU - Palyulin, Vladimir A.

AU - Ishmukhametov, Aydar A

AU - Shirshin, Evgeny

AU - Osolodkin, Dmitry I.

AU - Shtro, Anna A

AU - Kozlovskaya, Liubov I.

AU - Alferova, Vera A

AU - Ustinov, A.V.

PY - 2023

DA - 2023/01/01 00:00:00

PB - Elsevier

SP - 105508

VL - 209

SN - 0166-3542

SN - 1872-9096

ER -

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BibTex Copy

@article{2023_Chistov,

author = {Alexey A. Chistov and С. П. Чумаков and Igor E. Mikhnovets and Timofei D Nikitin and Nikita A. Slesarchuk and Victoria I Uvarova and Anna A Rubekina and Yulia Nikolaeva and Eugene V. Radchenko and Evgeny V. Khvatov and Alexey A. Orlov and Vasilisa S. Frolenko and Maksim V. Sukhorukov and Ekaterina S Kolpakova and Elena Yu. Shustova and Anastasiya V. Galochkina and Philipp P. Streshnev and Eugene M. Osipov and Ksenia A. Sapozhnikova and A V Moiseenko and V. A. Brylev and Gleb V Proskurin and Yuri S. Dokukin and Sergey V Kutyakov and Andrey V Aralov and Vladimir A. Korshun and Sergei V. Strelkov and Vladimir A. Palyulin and Aydar A Ishmukhametov and Evgeny Shirshin and Dmitry I. Osolodkin and Anna A Shtro and Liubov I. Kozlovskaya and Vera A Alferova and A.V. Ustinov},

title = {5-(Perylen-3-ylethynyl)uracil as an antiviral scaffold: Potent suppression of enveloped virus reproduction by 3-methyl derivatives in vitro},

journal = {Antiviral Research},

year = {2023},

volume = {209},

publisher = {Elsevier},

month = {jan},

url = {https://doi.org/10.1016%2Fj.antiviral.2022.105508},

pages = {105508},

doi = {10.1016/j.antiviral.2022.105508}

}

Found error?

Publisher

Elsevier

Journal

Antiviral Research

Quartile SCImago

Quartile WOS

Impact factor

7.6

ISSN

01663542 (Print)
18729096 (Electronic)

Labs

Laboratory of Antiviral medicines

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