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

Author:

Osolodkin Dmitry I.123,Kozlovskaya Liubov I.12,Iusupov Ildar R.3,Kurkin Alexander V.3,Shustova Elena Y.1,Orlov Alexey A.13,Khvatov Evgeny V.1,Mutnykh Elena S.1,Kurashova Svetlana S.1,Vetrova Anna N.1,Yatsenko Darya O.1,Goryashchenko Alexander S.1,Ivanov Vladimir N.3,Lukyanenko Evgeny R.3,Karpova Evgenia V.1,Stepanova Daria A.1,Volok Viktor P.1,Sotskova Svetlana E.1,Dzagurova Tamara K.1,Karganova Galina G.12,Lukashev Alexander N.12,Ishmukhametov Aydar A.12

Affiliation:

1. FSASI “Chumakov FSC R&D IBP RAS” (Institute of Poliomyelitis) Moscow Russia

2. Sechenov First Moscow State Medical University Moscow Russia

3. Department of Chemistry Lomonosov Moscow State University Moscow Russia

Abstract

AbstractEvolutionary 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.

Funder

Russian Science Foundation

Russian Foundation for Basic Research

Ministry of Science and Higher Education of the Russian Federation

Publisher

Wiley

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