Synthesis of 5-Halo-2ʹ-Azido Derivatives of Cytidine and N-Hydroxycytidine and Evaluation of Their Antiviral Activity on a Panel of RNA Viruses, Including SARS-CoV-2

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 COVID-19 and other viral diseases; in particular, molnupiravir has recently...

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Veröffentlicht in:Russian journal of bioorganic chemistry 2023-11, Vol.49 (6), p.1475-1482
Hauptverfasser: Kamzeeva, P. N., Kolpakova, E. S., Karpova, E. V., Borodulina, M. O., Yakovchuk, E. V., Alferova, V. A., Chistov, A. A., Belyaev, E. S., Kozlovskaya, L. I., Aralov, A. V.
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Sprache:eng
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Zusammenfassung: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 COVID-19 and other viral diseases; in particular, molnupiravir has recently been approved for emergency prophylaxis in the early stages after infection with SARS-CoV-2. In the present work, a scheme for the synthesis of 5-halo-2ʹ-azido-substituted cytidine and N -hydroxycytidine derivatives was proposed. The synthesized compounds were tested against a panel of six RNA viruses, including SARS-CoV-2, enteroviruses, CHIKV, and HIV-1. A number of compounds showed ability 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.
ISSN:1068-1620
1608-330X
DOI:10.1134/S1068162023060262