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10.1038/s41586-018-0238-4 http://scihub22266oqcxt.onion/10.1038/s41586-018-0238-4 C6026066!6026066!29925952     free     free     free Deprecated: Implicit conversion from float 225.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 225.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 225.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 225.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nature 2018 ; 558 (7711): 610-4 Nephropedia Template TP {{tp|p=29925952|t=2018. A naturally occurring antiviral ribonucleotide encoded by the human genome |pdf=|usr=}}{{29925952}} gab.com Text A naturally occurring antiviral ribonucleotide encoded by the human genome JO: Nature http://www.kidney.de/pget.php?&tw=1&pmid=29925952 #FOAvip Viral infections continue to represent major public health challenges, demanding enhanced mechanistic understanding of the processes contributing to viral lifecycles for the realization of new therapeutic strategies1. Viperin, a member of the radical S-adenosyl-L-methionine (SAM) superfamily of enzymes, is an interferon inducible protein implicated in inhibiting the replication of a remarkable range of RNA and DNA viruses, including dengue virus, West Nile virus, hepatitis C virus, influenza A virus, rabies virus2 and HIV3,4. Viperin has been suggested to elicit these broad antiviral activities through interactions with a large number of functionally unrelated host and viral proteins3,4. In contrast, herein, we demonstrate that viperin catalyzes the conversion of cytidine triphosphate (CTP) to 3?-deoxy-3?,4?-didehydro-CTP (ddhCTP), a previously undescribed biologically relevant molecule, via a SAM-dependent radical mechanism. We show that mammalian cells expressing viperin, and macrophages stimulated with IFN-?, produce substantial quantities of ddhCTP. We also establish that ddhCTP acts as a chain terminator for the RNA-dependent RNA-polymerases from multiple members of the flavivirus family, and present evidence that ddhCTP directly inhibits in vivo replication of ZIKA virus. These findings suggest a partially unifying mechanism, based on intrinsic catalytic/enzymatic properties, for the broad antiviral effects of viperin, which involves the generation of a naturally occurring replication chain terminator encoded by mammalian genomes. Twit Text FOAVip A naturally occurring antiviral ribonucleotide encoded by the human genome ????Nature http://www.kidney.de/pget.php?&tw=1&pmid=29925952 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29925952 #FOAvip English Wikipedia <ref>{{Cite pmid|29925952}}</ref> A naturally occurring antiviral ribonucleotide encoded by the human genome #MMPMID29925952 Gizzi AS; Grove TL; Arnold JJ; Jose J; Jangra RK; Garforth SJ; Du Q; Cahill SM; Dulyaninova NG; Love JD; Chandran K; Bresnick AR; Cameron CE; Almo SC Nature 2018[Jun]; 558 (7711): 610-4 PMID29925952show ga Viral infections continue to represent major public health challenges, demanding enhanced mechanistic understanding of the processes contributing to viral lifecycles for the realization of new therapeutic strategies1. Viperin, a member of the radical S-adenosyl-L-methionine (SAM) superfamily of enzymes, is an interferon inducible protein implicated in inhibiting the replication of a remarkable range of RNA and DNA viruses, including dengue virus, West Nile virus, hepatitis C virus, influenza A virus, rabies virus2 and HIV3,4. Viperin has been suggested to elicit these broad antiviral activities through interactions with a large number of functionally unrelated host and viral proteins3,4. In contrast, herein, we demonstrate that viperin catalyzes the conversion of cytidine triphosphate (CTP) to 3?-deoxy-3?,4?-didehydro-CTP (ddhCTP), a previously undescribed biologically relevant molecule, via a SAM-dependent radical mechanism. We show that mammalian cells expressing viperin, and macrophages stimulated with IFN-?, produce substantial quantities of ddhCTP. We also establish that ddhCTP acts as a chain terminator for the RNA-dependent RNA-polymerases from multiple members of the flavivirus family, and present evidence that ddhCTP directly inhibits in vivo replication of ZIKA virus. These findings suggest a partially unifying mechanism, based on intrinsic catalytic/enzymatic properties, for the broad antiviral effects of viperin, which involves the generation of a naturally occurring replication chain terminator encoded by mammalian genomes. äA naturally occurring antiviral ribonucleotide encoded by the human ge(epmc).pdf DeepDyve Pubget Overpricing