Selective Inhibition of Enterovirus A Species Members' Reproduction by Furano[2, 3- d]pyrimidine Nucleosides Revealed by Antiviral Activity Profiling against (+)ssRNA Viruses

Liubov I Kozlovskaya; Anastasia D Golinets; Anastasia A Eletskaya; Alexey A Orlov; Vladimir A Palyulin; Sergey N Kochetkov; Liudmila A Alexandrova; Dmitry I Osolodkin

doi:10.1002/slct.201703052

Selective Inhibition of Enterovirus A Species Members' Reproduction by Furano[2, 3- d]pyrimidine Nucleosides Revealed by Antiviral Activity Profiling against (+)ssRNA Viruses

ChemistrySelect. 2018 Feb 28;3(8):2321-2325. doi: 10.1002/slct.201703052. Epub 2018 Feb 27.

Authors

Liubov I Kozlovskaya^{1

2}, Anastasia D Golinets^{1

2}, Anastasia A Eletskaya^{1

3}, Alexey A Orlov^{1

3}, Vladimir A Palyulin³, Sergey N Kochetkov⁴, Liudmila A Alexandrova⁴, Dmitry I Osolodkin^{1

2

3}

Affiliations

¹ Institute of Poliomielitis and Viral Encephalitides FSBSI Chumakov FSC R&D IBP RAS Poselok Instituta Poliomielita, 8 bd. 1, Poselenie Moskovsky Moscow 108819 Russia.
² Sechenov First Moscow State Medical University, Trubetskaya ul., 8 Moscow 119991 Russia.
³ Lomonosov Moscow State University, Leninskie Gory, 1 Moscow 119991 Russia.
⁴ Engelhargt Institute of Molecular Biology Russian Academy of Sciences, Ul. Vavilova, 32 Moscow 119991 Russia.

Abstract

The rational design of broad-spectrum antivirals requires data on antiviral activity of compounds against multiple viruses, which are often not available. We have developed a panel of (+)ssRNA viruses composed of Enterovirus and Flavivirus genera members allowing to study these activity spectra. Antiviral activity profiling of a set of nucleoside analogues revealed N ⁴-hydroxycytidine as an efficient inhibitor of replication of coxsackieviruses and other enteroviruses, but ineffective against tick-borne encephalitis virus. Furano[2, 3-d]pyrimidine nucleosides with n-pentyl or n-hexyl tails showed selective inhibition of Enterovirus A representatives. 5-(Tetradec-1-yn-1-yl)-uridine showed selective inhibition of tick-borne encephalitis virus at the micromolar level.

Keywords: antiviral agents; enterovirus; nucleoside analogues; structure-activity relationships; tick-borne encephalitis virus.