Structure-activity relationships of nucleoside analogues for inhibition of tick-borne encephalitis virus

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F16%3A00465631" target="_blank" >RIV/61388963:_____/16:00465631 - isvavai.cz</a>

Alternative codes found

RIV/60077344:_____/16:00465631 RIV/00027162:_____/16:N0000116 RIV/60076658:12310/16:43890961

Result on the web

<a href="http://dx.doi.org/10.1016/j.antiviral.2016.07.018" target="_blank" >http://dx.doi.org/10.1016/j.antiviral.2016.07.018</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.antiviral.2016.07.018" target="_blank" >10.1016/j.antiviral.2016.07.018</a>

Result language

angličtina

Original language name

Structure-activity relationships of nucleoside analogues for inhibition of tick-borne encephalitis virus

Original language description

Tick-borne encephalitis (TBE) represents one of the most serious arboviral neuro-infections in Europe and northern Asia. As no specific antiviral therapy is available at present, there is an urgent need for efficient drugs to treat patients with TBE virus (TBEV) infection. Using two standardised in vitro assay systems, we evaluated a series of 29 nucleoside derivatives for their ability to inhibit TBEV replication in cell lines of neuronal as well as extraneural origin. The series of tested compounds included 2'-C- or 2'-O-methyl substituted nucleosides, 2'-C-fluoro-2'-C-methyl substituted nucleosides, 3'-O-methyl substituted nucleosides, 3'-deoxynucleosides, derivatives with 4'-C-azido substitution, heterobase modified nucleosides and neplanocins. Our data demonstrate a relatively stringent structure-activity relationship for modifications at the 2', 3', and 4' nucleoside positions. Whereas nucleoside derivatives with the methylation at the C2' position or azido modification at the C4'position exerted a strong TBEV inhibition activity (EC50 from 0.3 to 11.1 mu M) and low cytotoxicity in vitro, substitutions of the O2' and O3' positions led to a complete loss of anti-TBEV activity (EC50 > 50 mu M). Moreover, some structural modifications of the heterobase moiety resulted in a high increase of cytotoxicity in vitro. High antiviral activity and low cytotoxicity of C2' methylated or C4' azido substituted pharmacophores suggest that such compounds might represent promising candidates for further development of potential therapeutic agents in treating TBEV infection.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

CC - Organic chemistry

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Antiviral Research

ISSN

0166-3542

e-ISSN

—

Volume of the periodical

133

Issue of the periodical within the volume

Sep

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

11

Pages from-to

119-129

UT code for WoS article

000384856200014

EID of the result in the Scopus database

2-s2.0-84982836748