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10.1038/s41598-020-73641-9 http://scihub22266oqcxt.onion/10.1038/s41598-020-73641-9 33024223!7538426!33024223     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=33024223&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215 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 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 259.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Sci+Rep 2020 ; 10 (1): 16577 Nephropedia Template TP {{tp|p=33024223|t=2020. Sofosbuvir terminated RNA is more resistant to SARS-CoV-2 proofreader than RNA terminated by Remdesivir |pdf=|usr=}}{{33024223}} gab.com Text Sofosbuvir terminated RNA is more resistant to SARS-CoV-2 proofreader than RNA terminated by Remdesivir JO: Sci Rep http://www.kidney.de/pget.php?&tw=1&pmid=33024223 #FOAvip SARS-CoV-2 is responsible for COVID-19, resulting in the largest pandemic in over a hundred years. After examining the molecular structures and activities of hepatitis C viral inhibitors and comparing hepatitis C virus and coronavirus replication, we previously postulated that the FDA-approved hepatitis C drug EPCLUSA (Sofosbuvir/Velpatasvir) might inhibit SARS-CoV-2. We subsequently demonstrated that Sofosbuvir triphosphate is incorporated by the relatively low fidelity SARS-CoV and SARS-CoV-2 RNA-dependent RNA polymerases (RdRps), serving as an immediate polymerase reaction terminator, but not by a host-like high fidelity DNA polymerase. Other investigators have since demonstrated the ability of Sofosbuvir to inhibit SARS-CoV-2 replication in lung and brain cells; additionally, COVID-19 clinical trials with EPCLUSA and with Sofosbuvir plus Daclatasvir have been initiated in several countries. SARS-CoV-2 has an exonuclease-based proofreader to maintain the viral genome integrity. Any effective antiviral targeting the SARS-CoV-2 RdRp must display a certain level of resistance to this proofreading activity. We report here that Sofosbuvir terminated RNA resists removal by the exonuclease to a substantially higher extent than RNA terminated by Remdesivir, another drug being used as a COVID-19 therapeutic. These results offer a molecular basis supporting the current use of Sofosbuvir in combination with other drugs in COVID-19 clinical trials. Twit Text FOAVip Sofosbuvir terminated RNA is more resistant to SARS-CoV-2 proofreader than RNA terminated by Remdesivir ????Sci Rep http://www.kidney.de/pget.php?&tw=1&pmid=33024223 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33024223 #FOAvip English Wikipedia <ref>{{Cite pmid|33024223}}</ref> Sofosbuvir terminated RNA is more resistant to SARS-CoV-2 proofreader than RNA terminated by Remdesivir #MMPMID33024223 Jockusch S; Tao C; Li X; Chien M; Kumar S; Morozova I; Kalachikov S; Russo JJ; Ju J Sci Rep 2020[Oct]; 10 (1): 16577 PMID33024223show ga SARS-CoV-2 is responsible for COVID-19, resulting in the largest pandemic in over a hundred years. After examining the molecular structures and activities of hepatitis C viral inhibitors and comparing hepatitis C virus and coronavirus replication, we previously postulated that the FDA-approved hepatitis C drug EPCLUSA (Sofosbuvir/Velpatasvir) might inhibit SARS-CoV-2. We subsequently demonstrated that Sofosbuvir triphosphate is incorporated by the relatively low fidelity SARS-CoV and SARS-CoV-2 RNA-dependent RNA polymerases (RdRps), serving as an immediate polymerase reaction terminator, but not by a host-like high fidelity DNA polymerase. Other investigators have since demonstrated the ability of Sofosbuvir to inhibit SARS-CoV-2 replication in lung and brain cells; additionally, COVID-19 clinical trials with EPCLUSA and with Sofosbuvir plus Daclatasvir have been initiated in several countries. SARS-CoV-2 has an exonuclease-based proofreader to maintain the viral genome integrity. Any effective antiviral targeting the SARS-CoV-2 RdRp must display a certain level of resistance to this proofreading activity. We report here that Sofosbuvir terminated RNA resists removal by the exonuclease to a substantially higher extent than RNA terminated by Remdesivir, another drug being used as a COVID-19 therapeutic. These results offer a molecular basis supporting the current use of Sofosbuvir in combination with other drugs in COVID-19 clinical trials. |Adenosine Monophosphate/*analogs & derivatives/chemistry/pharmacology/therapeutic use[MESH] |Alanine/*analogs & derivatives/chemistry/pharmacology/therapeutic use[MESH] |Antiviral Agents/chemistry/*pharmacology/therapeutic use[MESH] |Betacoronavirus/*drug effects/enzymology[MESH] |COVID-19[MESH] |Coronavirus Infections/*drug therapy/virology[MESH] |Coronavirus RNA-Dependent RNA Polymerase[MESH] |Drug Discovery/methods[MESH] |Drug Repositioning/methods[MESH] |Exonucleases/*metabolism[MESH] |Hepacivirus/drug effects/enzymology[MESH] |Hepatitis C/drug therapy/virology[MESH] |Humans[MESH] |Pandemics[MESH] |Pneumonia, Viral/*drug therapy/virology[MESH] |Prodrugs/*pharmacology/therapeutic use[MESH] |RNA, Viral/chemistry/*drug effects/metabolism[MESH] |RNA-Dependent RNA Polymerase/antagonists & inhibitors/metabolism[MESH] |SARS-CoV-2[MESH] |Sofosbuvir/chemistry/*pharmacology/therapeutic use[MESH] |Viral Nonstructural Proteins/antagonists & inhibitors/metabolism[MESH]Sofosbuvir terminated RNA is more resistant to SARS-CoV-2 proofreader (epmc).pdf DeepDyve Pubget Overpricing