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

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.