Phenotypic assessment of antiviral activity for spiro‐annulated oxepanes and azepenes

Evolutionary potential of viruses can result in outbreaks of well‐known viruses and emergence of novel ones. Pharmacological methods of intervening the reproduction of various less popular, but not less important viruses are not available, as well as the spectrum of antiviral activity for most known...

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Veröffentlicht in:Chemical biology & drug design 2024-05, Vol.103 (5), p.e14553-n/a
Hauptverfasser: Osolodkin, Dmitry I., Kozlovskaya, Liubov I., Iusupov, Ildar R., Kurkin, Alexander V., Shustova, Elena Y., Orlov, Alexey A., Khvatov, Evgeny V., Mutnykh, Elena S., Kurashova, Svetlana S., Vetrova, Anna N., Yatsenko, Darya O., Goryashchenko, Alexander S., Ivanov, Vladimir N., Lukyanenko, Evgeny R., Karpova, Evgenia V., Stepanova, Daria A., Volok, Viktor P., Sotskova, Svetlana E., Dzagurova, Tamara K., Karganova, Galina G., Lukashev, Alexander N., Ishmukhametov, Aydar A.
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container_issue 5
container_start_page e14553
container_title Chemical biology & drug design
container_volume 103
creator Osolodkin, Dmitry I.
Kozlovskaya, Liubov I.
Iusupov, Ildar R.
Kurkin, Alexander V.
Shustova, Elena Y.
Orlov, Alexey A.
Khvatov, Evgeny V.
Mutnykh, Elena S.
Kurashova, Svetlana S.
Vetrova, Anna N.
Yatsenko, Darya O.
Goryashchenko, Alexander S.
Ivanov, Vladimir N.
Lukyanenko, Evgeny R.
Karpova, Evgenia V.
Stepanova, Daria A.
Volok, Viktor P.
Sotskova, Svetlana E.
Dzagurova, Tamara K.
Karganova, Galina G.
Lukashev, Alexander N.
Ishmukhametov, Aydar A.
description Evolutionary potential of viruses can result in outbreaks of well‐known viruses and emergence of novel ones. Pharmacological methods of intervening the reproduction of various less popular, but not less important viruses are not available, as well as the spectrum of antiviral activity for most known compounds. In the framework of chemical biology paradigm, characterization of antiviral activity spectrum of new compounds allows to extend the antiviral chemical space and provides new important structure–activity relationships for data‐driven drug discovery. Here we present a primary assessment of antiviral activity of spiro‐annulated derivatives of seven‐membered heterocycles, oxepane and azepane, in phenotypic assays against viruses with different genomes, virion structures, and genome realization schemes: orthoflavivirus (tick‐borne encephalitis virus, TBEV), enteroviruses (poliovirus, enterovirus A71, echovirus 30), adenovirus (human adenovirus C5), hantavirus (Puumala virus). Hit compounds inhibited reproduction of adenovirus C5, the only DNA virus in the studied set, in the yield reduction assay, and did not inhibit reproduction of RNA viruses. Diversity‐oriented antiviral activity screening revealed adenovirus yield reduction by a structurally novel chemotype of spiro‐annulated oxepanes and azepenes.
doi_str_mv 10.1111/cbdd.14553
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subjects 2,3,4,7‐tetrahydrooxepine
2,3,4,7‐tetrahydro‐1H‐azepine
adenovirus
Animals
antiviral activity
Antiviral Agents - chemistry
Antiviral Agents - pharmacology
azepane
Humans
oxepane
Oxepins - chemistry
Oxepins - pharmacology
Phenotype
phenotypic screening
Spiro Compounds - chemistry
Spiro Compounds - pharmacology
spirocycle
Structure-Activity Relationship
Virus Replication - drug effects
title Phenotypic assessment of antiviral activity for spiro‐annulated oxepanes and azepenes
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