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

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Resumo

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.

Sobre autores

P. Kamzeeva

Institute of Bioorganic Chemistry, Russian Academy of Sciences

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

L. 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. Belyaev

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

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

A. Chistov

Institute of Bioorganic Chemistry, Russian Academy of Sciences

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

V. Alferova

Institute of Bioorganic Chemistry, Russian Academy of Sciences

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

E. 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. 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. 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. 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. Aralov

Sechenov First Moscow State Medical University

Autor responsável pela correspondência
Email: Baruh238@mail.ru
Russia, 119991, Moscow, ul. Trubetskaya 8/2

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Declaração de direitos autorais © 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, 2023