Viral genome cleavage with artificial ribonucleases: A new method to inactivate RNA-containing viruses

Novel amphiphilic compounds effectively inactivate the vaccinia virus

“…The aRNases were recently shown to display the antiviral activity against RNA‐containing viruses: inactivation of non‐enveloped ABPV was caused by the viral RNA cleavage [2], and inactivation of the enveloped influenza virus was due to the RNA cleavage and membrane distortion [1,9]. As the role of the membranolytic activity of aRNases in the overall antiviral activity of the compound was evident, in the present study we tested the ability of aRNases to inactivate DNA‐containing virus.…”

“…The ability of three different aRNases (Table 1) to inactivate DNA-containing vaccinia virus was tested. The synthesis, biochemical activity of the compounds [7,8,[12][13][14][15], as well as the antiviral activity against RNA-containing viruses [1,2,6,9] were described previously. The vaccinia virus at a concentration $5Á10 5 PFU/ml was incubated at physiological conditions in the presence of one of the aRNases ABL3C3, Dtr12, L2-3 or in the absence of the compounds for 0-72 h at 37°C.…”

“…These aRNases were of ABLkCm series, containing imidazole as catalytic group for the RNA cleavage, and positively charged 1,4‐diazabicyclo[2.2.2] octane (DABCO) substituted at the bridge nitrogens with dodecyl residues, affording the affinity to phosphodiester bonds of RNA (ABL3C3, Table 1 ) [7]; the compounds of the Dxn series, which contain two similarly substituted DABCO residues and no potentially catalytic groups (Dtr12, Table 1); and peptide‐like molecules containing amino acids as catalytic groups and hydrophobic substituents (L2–3, Table 1) [8]. It was demonstrated that the viral RNA of ABL3C3‐ and Dtr12‐inactivated influenza virus was cleaved, and the membrane of the inactivated virus particles contained a number of breaks (EM data) [1], but the surface peplomers were not affected [9]. The inactivation of influenza virus with peptide‐like compound L2–3 being complete did not result in the prominent cleavage of viral RNA [9].…”

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a b s t r a c tRecent studies demonstrated the ability of artificial ribonucleases (aRNases, small organic RNA cleaving compounds) to inactivate RNA-viruses via the synergetic effect of viral RNA cleavage and disruption of viral envelope [1,2]. Herein, we describe the antiviral activity of aRNases against DNA-containing vaccinia virus: screening of aRNases of various structures revealed that amphiphilic compounds built of positively charged 1,4-diazabicyclo[2.2.2] octane substituted at the bridge nitrogen atoms with aliphatic residues efficiently inactivate this virus.

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Synthesis and structure–activity relationship of novel 1,4-diazabicyclo[2.2.2]octane derivatives as potent antimicrobial agents

“…However, DNA binding bisquaternary bisnaphtalimides that leads to the inhibition of DNA replication was demonstrated[42]. The study of the antiviral activity mechanism of DABCO-based compounds on the influenza virus revealed that such cleaving phosphodiester bonds of viral RNA[43]. Because of these facts, the other possible mechanism of antibacterial and antifungal activities of these QACs could be hypothesized.…”