Synthesis and Evaluation of the Antiviral Activity of 5-Halogen-2'-Azido-Substituted Derivatives of Cytidine and N-Hydroxycytidine on a Panel of RNA Viruses, Including SARS-CoV-2

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Coronavirus disease 2019 (COVID-19) is a new global pandemic with high morbidity and mortality caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). N-Hydroxycytidine derivatives show promise for combating viral diseases, and in particular, molnupiravir has recently been approved for emergency prophylaxis in the early stages after infection with SARS-CoV-2. Here, a scheme for the synthesis of 5‑halo-2'-azido-substituted derivatives of cytidine and N-hydroxycytidine is proposed. The synthesized compounds were tested on a panel of six RNA viruses, including SARS-CoV-2, enteroviruses, CHIKV, and HIV-1. A number of compounds were able to inhibit the reproduction of SARS-CoV-2 and CHIKV viruses in the micromolar range without noticeable cytotoxicity. The structures of the leader compounds can be used as a starting point for further design of antiviral agents.

About the authors

P. N. Kamzeeva

Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: Baruh238@mail.ru
Russia, 117997, Moscow, ul. Miklukho-Maklaya 16/10

L. I. Kozlovskaya

Chumakov Scientific Center for Research and Development of Immune-and-Biological Products, Russian Academy
of Sciences (Institute of Poliomyelitis), village of the Institute of Poliomyelitis; Sechenov First Moscow State Medical University

Email: Baruh238@mail.ru
Russia, 108819, Moscow, settlement Moskovskiy, 8/1; Russia, 119991, Moscow, ul. Trubetskaya 8/2

E. S. Belyaev

Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Science

Email: Baruh238@mail.ru
Russia, 119071, Moscow, Leninskiy prosp. 31

A. A. Chistov

Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: Baruh238@mail.ru
Russia, 117997, Moscow, ul. Miklukho-Maklaya 16/10

V. A. Alferova

Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: Baruh238@mail.ru
Russia, 117997, Moscow, ul. Miklukho-Maklaya 16/10

E. V. Yakovchuk

Chumakov Scientific Center for Research and Development of Immune-and-Biological Products, Russian Academy
of Sciences (Institute of Poliomyelitis), village of the Institute of Poliomyelitis; Sechenov First Moscow State Medical University

Email: Baruh238@mail.ru
Russia, 108819, Moscow, settlement Moskovskiy, 8/1; Russia, 119991, Moscow, ul. Trubetskaya 8/2

M. O. Borodulina

Chumakov Scientific Center for Research and Development of Immune-and-Biological Products, Russian Academy
of Sciences (Institute of Poliomyelitis), village of the Institute of Poliomyelitis; Sechenov First Moscow State Medical University

Email: Baruh238@mail.ru
Russia, 108819, Moscow, settlement Moskovskiy, 8/1; Russia, 119991, Moscow, ul. Trubetskaya 8/2

E. V. Karpova

Chumakov Scientific Center for Research and Development of Immune-and-Biological Products, Russian Academy
of Sciences (Institute of Poliomyelitis), village of the Institute of Poliomyelitis

Email: Baruh238@mail.ru
Russia, 108819, Moscow, settlement Moskovskiy, 8/1

E. S. Kolpakova

Chumakov Scientific Center for Research and Development of Immune-and-Biological Products, Russian Academy
of Sciences (Institute of Poliomyelitis), village of the Institute of Poliomyelitis

Email: Baruh238@mail.ru
Russia, 108819, Moscow, settlement Moskovskiy, 8/1

A. V. Aralov

Sechenov First Moscow State Medical University

Author for correspondence.
Email: Baruh238@mail.ru
Russia, 119991, Moscow, ul. Trubetskaya 8/2

References

  1. Holmes E.C., Goldstein S.A., Rasmussen A.L., Robertson D.L., Crits-Christoph A., Wertheim J.O., Anthony S.J., Barclay W.S., Boni M.F., Doherty P.C., Farrar J., Geoghegan J.L., Jiang X., Leibowitz J.L., Neil S.J.D., Skern T., Weiss S.R., Worobey M., Andersen K.G., Garry R.F., Rambaut A. // Cell. 2021. V. 184. P. 4848–4856. https://doi.org/10.1016/j.cell.2021.08.017
  2. Triggle C.R., Bansal D., Ding H., Islam M.M., Farag E.A.B.A., Hadi H.A., Sultan A.A. // Front. Immunol. 2021. V. 12. P. 631139. https://doi.org/10.3389/fimmu.2021.631139
  3. van de Leemput J., Han Z. // Mol. Cell. Biol. 2021. V. 41. P. 1–16. https://doi.org/10.1128/MCB.00185-21
  4. Khudhair Z.T., Shihab M.S., Hamah-Ameen B. // Russ. J. Bioorg. Chem. 2021. V. 47. P. 789–804. https://doi.org/10.1134/S1068162021040130
  5. Beigel J.H., Tomashek K.M., Dodd L.E., Mehta A.K., Zingman B.S., Kalil A.C., Hohmann E., Chu H.Y., Luetkemeyer A., Kline S., de Castilla D.L., Finberg R.W., Dierberg K., Tapson V., Hsieh L., Patterson T.F., Paredes R., Sweeney D.A., Short W.R., Touloumi G., Lye D.C., Ohmagari N., Oh M.-D., Ruiz-Palacios G.M., Benfield T., Fätkenheuer G., Kortepeter M.G., Atmar R.L., Creech C.B., Lundgren J., Babiker A.G., Pett S., Neaton J.D., Burgess T.H., Bonnett T., Green M., Makowski M., Osinusi A., Nayak S., Lane H.C. // N. Engl. J. Med. 2020. V. 383. P. 1813–1826. https://doi.org/10.1056/NEJMoa2007764
  6. Zhou S., Hill C.S., Sarkar S., Tse L.V., Woodburn B.M.D., Schinazi R.F., Sheahan T.P., Baric R.S., Heise M.T., Swanstrom R. // J. Infect. Dis. 2021. V. 224. P. 415–419. https://doi.org/10.1093/infdis/jiab247
  7. Amblard F., LeCher J.C., De R., Goh S.L., Li C., Kasthuri M., Biteau N., Zhou L., Tber Z., Downs-Bowen J., Zandi K., Schinazi R.F. // Pharmaceuticals 2022. V. 15. P. 1144. https://doi.org/10.3390/ph15091144
  8. Urakova N., Kuznetsova V., Crossman D.K., Sokratian A., Guthrie D.B., Kolykhalov A.A., Lockwood M.A., Natchus M.G., Crowley M.R., Painter G.R., Frolova E.I., Frolov I. // J. Virol. 2018. V. 92. P. e01965-17. https://doi.org/10.1128/JVI.01965-17
  9. Agostini M.L., Pruijssers A.J., Chappell J.D., Gribble J., Lu X., Andres E.L., Bluemling G.R., Lockwood M.A., Sheahan T.P., Sims A.C., Natchus M.G., Saindane M., Kolykhalov A.A., Painter G.R., Baric R.S., Denison M.R. // J. Virol. 2019. V. 93. P. e01348-19. https://doi.org/10.1128/JVI.01348-19
  10. Kabinger F., Stiller C., Schmitzová J., Dienemann C., Kokic G., Hillen H.S., Höbartner C., Cramer P. // Nat. Struct. Mol. Biol. 2021. V. 28. P. 740–746. https://doi.org/10.1038/s41594-021-00651-0
  11. Liu F., Chen H.-M., Armstrong Z., Withers S.G. // ACS Cent. Sci. 2022. V. 8. P. 656–662. https://doi.org/10.1021/acscentsci.1c01172
  12. Chen F.-F., Wang F. // Molecules 2009. V. 14. P. 2656–2668. https://doi.org/10.3390/molecules14072656
  13. Wnuk S.F., Chowdhury S.M., Garcia P.I., Robins M.J. // J. Org. Chem. 2002. V. 67. P. 1816–1819. https://doi.org/10.1021/jo010899i
  14. Fedeles B.I., Freudenthal B.D., Yau E., Singh V., Chang S., Li D., Delaney J.C., Wilson S.H., Essigmann J.M. // Proc. Natl. Acad. Sci. USA. 2015. V. 112. P. 4571–4580. https://doi.org/10.1073/pnas.1507709112
  15. Moffatt J.G., Verheyden J.P.H., Wagner D. // J. Org. Chem. 1971. V. 36. P. 250–254. https://doi.org/10.1021/jo00801a002
  16. Asakura J., Robins M.J. // J. Org. Chem. 1990. V. 55. P. 4928–4933. https://doi.org/10.1021/jo00303a033
  17. McGee D.P.C., Vargeese C., Zhai Y.S., Kirschenheuter G.P., Settle A., Siedem C.R., Pieken W.A. // Nucleosides and Nucleotides. 1995. V. 14. P. 1329–1339. https://doi.org/10.1080/15257779508010694
  18. Mieczkowski A., Wińska P., Kaczmarek M., Mroczkowska M., Garbicz D., Pilżys T., Marcinkowski M., Piwowarski J., Grzesiuk E. // Chem. Pap. 2018. V. 72. P. 981–990. https://doi.org/10.1007/s11696-017-0339-9
  19. Paymode D.J., Vasudevan N., Ahmad S., Kadam A.L., Cardoso F.S.P., Burns J.M., Cook D.W., Stringham R.W., Snead D.R. // Org. Process Res. Dev. 2021. V. 25. P. 1822–1830. https://doi.org/10.1021/acs.oprd.1c00219
  20. Sheahan T.P., Sims A.C., Zhou S., Graham R.L., Pruijssers A.J., Agostini M.L., Leist S.R., Schäfer A., Dinnon K.H., Stevens L.J., Chappell J.D., Lu X., Hughes T.M., George A.S., Hill C.S., Montgomery S.A., Brown A.J., Bluemling G.R., Natchus M.G., Saindane M., Kolykhalov A.A., Painter G., Harcourt J., Tamin A., Thornburg N.J., Swanstrom R., Denison M.R., Baric R.S. // Sci. Transl. Med. 2020. V. 12. P. eabb5883. https://doi.org/10.1126/scitranslmed.abb5883
  21. Mitsuya H., Weinhold K.J., Furman P.A., St Clair M.H., Lehrman S.N., Gallo R.C., Bolognesi D., Barry D.W., Broder S. // Proc. Natl. Acad. Sci. USA. 1985. V. 82. P. 7096–7100. https://doi.org/10.1073/pnas.82.20.7096
  22. Fischl M.A., Richman D.D., Grieco M.H., Gottlieb M.S., Volberding P.A., Laskin O.L., Leedom J.M., Groopman J.E., Mildvan D., Schooley R.T., Jackson G.G., Durack D.T., King D. // N. Engl. J. Med. 1987. V. 317 P. 185–191. https://doi.org/10.1056/NEJM198707233170401
  23. Kozlovskaya L.I., Volok V.P., Shtro A.A., Nikolaeva Y.V., Chistov A.A., Matyugina E.S., Belyaev E.S., Jegorov A.V., Snoeck R., Korshun V.A., Andrei G., Osolodkin D.I., Ishmukhametov A.A., Aralov A.V. // Eur. J. Med. Chem. 2021. V. 220. P. 113467. https://doi.org/10.1016/j.ejmech.2021.113467
  24. Kärber G. // Arch. Exp. Pathol. Pharmakol. 1931. V. 162. P. 480–483.
  25. Ryazantsev D.Y., Myshkin M.Yu., Alferova V.A., Tsvetkov V.B., Shustova E.Y., Kamzeeva P.N., Kovalets P.V., Zaitseva E.R., Baleeva N.S., Zatsepin T.S., Baleeva N.S., Zatsepin T.S., Shenkarev Z.O., Baranov M.S., Kozlovskaya L.I., Aralov A.V. // Biomolecules 2021. V. 11. P. 1409. https://doi.org/10.3390/biom11101409
  26. Zenchenko A.A., Oslovsky V.E., Varizhuk I.V., Karpova E.V., Osolodkin D.I., Kozlovskaya L.I., Ishmukhametov A.A., Drenichev M.S. // Toxicol. In Vitro. 2022. V. 82. P. 105 355. https://doi.org/10.1016/j.tiv.2022.105355

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2.

Download (53KB)
Indexing metadata

Copyright (c) 2023 П.Н. Камзеева, Е.С. Колпакова, Е.В. Карпова, М.О. Бородулина, Е.В. Яковчук, В.А. Алферова, А.А. Чистов, Е.С. Беляев, Л.И. Козловская, А.В. Аралов