title: Artificial ribonucleases inactivate a wide range of viruses using their ribonuclease, membranolytic, and chaotropic-like activities.
abstract: Artificial ribonucleases (aRNases) are small compounds catalysing RNA cleavage. Recently we demonstrated that aRNases readily inactivate various viruses in vitro. Here, for three series of aRNases (1,4-diazabicyclo [2.2.2]octane-based and peptide-like compounds) we show that apart from ribonuclease activity the aRNases display chaotropic-like and membranolytic activities. The levels of membranolytic and chaotropic-like activities correlate well with the efficiency of various viruses inactivation (enveloped, non-enveloped, RNA-, DNA-containing). We evaluated the impact of these activities on the efficiency of virus inactivation and found: i) the synergism between membranolytic and chaotropic-like activities is sufficient for the inactivation of enveloped viruses (influenza A, encephalitis, vaccinia viruses) for 1,4-diazabicyclo [2.2.2]octane based aRNases, ii) the inactivation of non-enveloped viruses (encephalomyocarditis, acute bee paralysis viruses) is totally dependent on the synergism of chaotropic-like and ribonuclease activities, iii) ribonuclease activity plays a leading role in the inactivation of RNA viruses by aRNases Dp12F6, Dtr12 and K-D-1, iv) peptide-like aRNases (L2-3, K-2) being effective virus killers have a more specific mode of action. Obtained results clearly demonstrate that aRNases represent a new class of broad-spectrum virus-inactivating agents.
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 8, Lavrentiev Ave., Novosibirsk, 630090, Russian Federation.
authors.forename: Antonina A
authors.initials: AA
authors.lastname: Fedorova
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 8, Lavrentiev Ave., Novosibirsk, 630090, Russian Federation.
authors.forename: Elena P
authors.initials: EP
authors.lastname: Goncharova
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 8, Lavrentiev Ave., Novosibirsk, 630090, Russian Federation.
authors.forename: Lyudmila S
authors.initials: LS
authors.lastname: Koroleva
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 8, Lavrentiev Ave., Novosibirsk, 630090, Russian Federation.
authors.forename: Ekatherina A
authors.initials: EA
authors.lastname: Burakova
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 8, Lavrentiev Ave., Novosibirsk, 630090, Russian Federation.
authors.forename: Elena I
authors.initials: EI
authors.lastname: Ryabchikova
authors.affiliation: School of Pharmacy, University of Manchester, Oxford Road, M13 9PT, Manchester, United Kingdom.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Bichenkova
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 8, Lavrentiev Ave., Novosibirsk, 630090, Russian Federation.
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Silnikov
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 8, Lavrentiev Ave., Novosibirsk, 630090, Russian Federation.
authors.forename: Valentin V
authors.initials: VV
authors.lastname: Vlassov
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 8, Lavrentiev Ave., Novosibirsk, 630090, Russian Federation. Electronic address: marzen@niboch.nsc.ru.
authors.forename: Marina A
authors.initials: MA
authors.lastname: Zenkova
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D015394:Molecular Structure; D012260:Ribonucleases / Q000737:chemistry / Q000494:pharmacology*; D014616:Vaccinia virus / Q000187:drug effects; D038301:Virus Inactivation / Q000187:drug effects*; D014780:Viruses / Q000187:drug effects* / Q000648:ultrastructure
chemical_list: D000998:Antiviral Agents; D012260:Ribonucleases
keywords: ABPV; Artificial ribonucleases; Chaotropic-like activity; Encephalitis virus; Influenza virus; Membranolytic activity; Ribonuclease activity; Vaccinia virus; Virus inactivation