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10.1371/journal.ppat.1001163 http://scihub22266oqcxt.onion/10.1371/journal.ppat.1001163 21060812!2965762!21060812     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       PLoS+Pathog 2010 ; 6 (10): e1001163 Nephropedia Template TP {{tp|p=21060812|t=2010. Fidelity variants of RNA dependent RNA polymerases uncover an indirect, mutagenic activity of amiloride compounds |pdf=|usr=}}{{21060812}} gab.com Text Fidelity variants of RNA dependent RNA polymerases uncover an indirect, mutagenic activity of amiloride compounds JO: PLoS Pathog http://www.kidney.de/pget.php?&tw=1&pmid=21060812 #FOAvip In a screen for RNA mutagen resistance, we isolated a high fidelity RNA dependent RNA polymerase (RdRp) variant of Coxsackie virus B3 (CVB3). Curiously, this variant A372V is also resistant to amiloride. We hypothesize that amiloride has a previously undescribed mutagenic activity. Indeed, amiloride compounds increase the mutation frequencies of CVB3 and poliovirus and high fidelity variants of both viruses are more resistant to this effect. We hypothesize that this mutagenic activity is mediated through alterations in intracellular ions such as Mg(2)+ and Mn(2)+, which in turn increase virus mutation frequency by affecting RdRp fidelity. Furthermore, we show that another amiloride-resistant RdRp variant, S299T, is completely resistant to this mutagenic activity and unaffected by changes in ion concentrations. We show that RdRp variants resist the mutagenic activity of amiloride via two different mechanisms: 1) increased fidelity that generates virus populations presenting lower basal mutation frequencies or 2) resisting changes in divalent cation concentrations that affect polymerase fidelity. Our results uncover a new antiviral approach based on mutagenesis. Twit Text FOAVip Fidelity variants of RNA dependent RNA polymerases uncover an indirect, mutagenic activity of amiloride compounds ????PLoS Pathog http://www.kidney.de/pget.php?&tw=1&pmid=21060812 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=21060812 #FOAvip English Wikipedia <ref>{{Cite pmid|21060812}}</ref> Fidelity variants of RNA dependent RNA polymerases uncover an indirect, mutagenic activity of amiloride compounds #MMPMID21060812 Levi LI; Gnadig NF; Beaucourt S; McPherson MJ; Baron B; Arnold JJ; Vignuzzi M PLoS Pathog 2010[Oct]; 6 (10): e1001163 PMID21060812show ga In a screen for RNA mutagen resistance, we isolated a high fidelity RNA dependent RNA polymerase (RdRp) variant of Coxsackie virus B3 (CVB3). Curiously, this variant A372V is also resistant to amiloride. We hypothesize that amiloride has a previously undescribed mutagenic activity. Indeed, amiloride compounds increase the mutation frequencies of CVB3 and poliovirus and high fidelity variants of both viruses are more resistant to this effect. We hypothesize that this mutagenic activity is mediated through alterations in intracellular ions such as Mg(2)+ and Mn(2)+, which in turn increase virus mutation frequency by affecting RdRp fidelity. Furthermore, we show that another amiloride-resistant RdRp variant, S299T, is completely resistant to this mutagenic activity and unaffected by changes in ion concentrations. We show that RdRp variants resist the mutagenic activity of amiloride via two different mechanisms: 1) increased fidelity that generates virus populations presenting lower basal mutation frequencies or 2) resisting changes in divalent cation concentrations that affect polymerase fidelity. Our results uncover a new antiviral approach based on mutagenesis. |Amiloride/*adverse effects/analogs & derivatives/pharmacology[MESH] |Animals[MESH] |Antiviral Agents/adverse effects/pharmacology[MESH] |Base Sequence[MESH] |Chlorocebus aethiops[MESH] |DNA-Directed RNA Polymerases/*metabolism[MESH] |Enterovirus/genetics[MESH] |Genetic Variation/drug effects[MESH] |HeLa Cells[MESH] |Humans[MESH] |Mutagenesis/*drug effects[MESH] |Mutagens/pharmacology[MESH] |RNA, Viral/drug effects/genetics[MESH] |RNA/*genetics/metabolism[MESH] |Templates, Genetic[MESH] |Transcription, Genetic/*drug effects/genetics[MESH]Fidelity variants of RNA dependent RNA polymerases uncover an indirect(epmc).pdf DeepDyve Pubget Overpricing