New tools in nucleoside toolbox of tick-borne encephalitis virus reproduction inhibitors.
Design and development of nucleoside analogs is an established strategy in the antiviral drug discovery field. Nevertheless, for many viruses the coverage of structure-activity relationships (SAR) in the nucleoside chemical space is not sufficient. Here we present the nucleoside SAR exploration for tick-borne encephalitis virus (TBEV), a member of Flavivirus genus. Promising antiviral activity may be achieved by introduction of large hydrophobic substituents in the position 6 of adenosine or bulky silyl groups to the position 5'. Introduction of methyls to the ribose moiety does not lead to inhibition of TBEV reproduction. Possible mechanisms of action of these nucleosides include the inhibition of viral entry or interaction with TBEV non-structural protein 5 methyltransferase or RNA-dependent RNA polymerase domains.
Chumakov Institute of Poliomyelitis and Viral Encephalitides, Chumakov FSC R&D IBP RAS, 8 bd. 1, Poselok Instituta Poliomielita, Poselenie Moskovsky, Moscow 108819, Russia; Department of Chemistry, Lomonosov Moscow State University, 1 bd. 3 Leninskie Gory, Moscow 119991, Russia.
Alexey A
AA
Orlov
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 32 Vavilova Str., Moscow 119991, Russia.
Mikhail S
MS
Drenichev
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 32 Vavilova Str., Moscow 119991, Russia.
Vladimir E
VE
Oslovsky
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 32 Vavilova Str., Moscow 119991, Russia.
Nikolay N
NN
Kurochkin
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 32 Vavilova Str., Moscow 119991, Russia.
Pavel N
PN
Solyev
Chumakov Institute of Poliomyelitis and Viral Encephalitides, Chumakov FSC R&D IBP RAS, 8 bd. 1, Poselok Instituta Poliomielita, Poselenie Moskovsky, Moscow 108819, Russia.
Liubov I
LI
Kozlovskaya
Department of Chemistry, Lomonosov Moscow State University, 1 bd. 3 Leninskie Gory, Moscow 119991, Russia.
Vladimir A
VA
Palyulin
Chumakov Institute of Poliomyelitis and Viral Encephalitides, Chumakov FSC R&D IBP RAS, 8 bd. 1, Poselok Instituta Poliomielita, Poselenie Moskovsky, Moscow 108819, Russia.
Galina G
GG
Karganova
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 32 Vavilova Str., Moscow 119991, Russia.
Sergey N
SN
Mikhailov
Chumakov Institute of Poliomyelitis and Viral Encephalitides, Chumakov FSC R&D IBP RAS, 8 bd. 1, Poselok Instituta Poliomielita, Poselenie Moskovsky, Moscow 108819, Russia; Department of Chemistry, Lomonosov Moscow State University, 1 bd. 3 Leninskie Gory, Moscow 119991, Russia. Electronic address: dmitry_o@qsar.chem.msu.ru.
Dmitry I
DI
Osolodkin
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004669:Encephalitis Viruses, Tick-Borne / Q000187:drug effects*; D006801:Humans; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D053586:Virus Internalization / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D009705:Nucleosides
Antivirals; Flavivirus; Nucleosides; Tick-borne encephalitis