Use my Search Websuite to scan PubMed, PMCentral, Journal Hosts and Journal Archives, FullText. Kick-your-searchterm to multiple Engines kick-your-query now !>

A dictionary by aggregated review articles of nephrology, medicine and the life sciences Your one-stop-run pathway from word to the immediate pdf of peer-reviewed on-topic knowledge.

10.1002/prp2.674 http://scihub22266oqcxt.onion/10.1002/prp2.674 33124786!7596664!33124786     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Pharmacol+Res+Perspect 2020 ; 8 (6): e00674 Nephropedia Template TP {{tp|p=33124786|t=2020. Nucleotide analogues as inhibitors of SARS-CoV Polymerase |pdf=|usr=}}{{33124786}} gab.com Text Nucleotide analogues as inhibitors of SARS-CoV Polymerase JO: Pharmacol Res Perspect http://www.kidney.de/pget.php?&tw=1&pmid=33124786 #FOAvip SARS-CoV-2, a member of the coronavirus family, has caused a global public health emergency. Based on our analysis of hepatitis C virus and coronavirus replication, and the molecular structures and activities of viral inhibitors, we previously reasoned that the FDA-approved hepatitis C drug EPCLUSA (Sofosbuvir/Velpatasvir) should inhibit coronaviruses, including SARS-CoV-2. Here, using model polymerase extension experiments, we demonstrate that the active triphosphate form of Sofosbuvir is incorporated by low-fidelity polymerases and SARS-CoV RNA-dependent RNA polymerase (RdRp), and blocks further incorporation by these polymerases; the active triphosphate form of Sofosbuvir is not incorporated by a host-like high-fidelity DNA polymerase. Using the same molecular insight, we selected 3'-fluoro-3'-deoxythymidine triphosphate and 3'-azido-3'-deoxythymidine triphosphate, which are the active forms of two other anti-viral agents, Alovudine and AZT (an FDA-approved HIV/AIDS drug) for evaluation as inhibitors of SARS-CoV RdRp. We demonstrate the ability of two of these HIV reverse transcriptase inhibitors to be incorporated by SARS-CoV RdRp where they also terminate further polymerase extension. Given the 98% amino acid similarity of the SARS-CoV and SARS-CoV-2 RdRps, we expect these nucleotide analogues would also inhibit the SARS-CoV-2 polymerase. These results offer guidance to further modify these nucleotide analogues to generate more potent broad-spectrum anti-coronavirus agents. Twit Text FOAVip Nucleotide analogues as inhibitors of SARS-CoV Polymerase ????Pharmacol Res Perspect http://www.kidney.de/pget.php?&tw=1&pmid=33124786 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33124786 #FOAvip English Wikipedia <ref>{{Cite pmid|33124786}}</ref> Nucleotide analogues as inhibitors of SARS-CoV Polymerase #MMPMID33124786 Ju J; Li X; Kumar S; Jockusch S; Chien M; Tao C; Morozova I; Kalachikov S; Kirchdoerfer RN; Russo JJ Pharmacol Res Perspect 2020[Dec]; 8 (6): e00674 PMID33124786show ga SARS-CoV-2, a member of the coronavirus family, has caused a global public health emergency. Based on our analysis of hepatitis C virus and coronavirus replication, and the molecular structures and activities of viral inhibitors, we previously reasoned that the FDA-approved hepatitis C drug EPCLUSA (Sofosbuvir/Velpatasvir) should inhibit coronaviruses, including SARS-CoV-2. Here, using model polymerase extension experiments, we demonstrate that the active triphosphate form of Sofosbuvir is incorporated by low-fidelity polymerases and SARS-CoV RNA-dependent RNA polymerase (RdRp), and blocks further incorporation by these polymerases; the active triphosphate form of Sofosbuvir is not incorporated by a host-like high-fidelity DNA polymerase. Using the same molecular insight, we selected 3'-fluoro-3'-deoxythymidine triphosphate and 3'-azido-3'-deoxythymidine triphosphate, which are the active forms of two other anti-viral agents, Alovudine and AZT (an FDA-approved HIV/AIDS drug) for evaluation as inhibitors of SARS-CoV RdRp. We demonstrate the ability of two of these HIV reverse transcriptase inhibitors to be incorporated by SARS-CoV RdRp where they also terminate further polymerase extension. Given the 98% amino acid similarity of the SARS-CoV and SARS-CoV-2 RdRps, we expect these nucleotide analogues would also inhibit the SARS-CoV-2 polymerase. These results offer guidance to further modify these nucleotide analogues to generate more potent broad-spectrum anti-coronavirus agents. |Antiviral Agents/*pharmacology[MESH] |Betacoronavirus/*drug effects/enzymology[MESH] |COVID-19[MESH] |Carbamates/pharmacology[MESH] |Coronavirus Infections/*drug therapy/virology[MESH] |Dideoxynucleotides/pharmacology[MESH] |Drug Combinations[MESH] |Heterocyclic Compounds, 4 or More Rings/pharmacology[MESH] |Humans[MESH] |Pandemics[MESH] |Pneumonia, Viral/*drug therapy/virology[MESH] |RNA-Dependent RNA Polymerase/*antagonists & inhibitors[MESH] |SARS-CoV-2[MESH] |Sofosbuvir/pharmacology[MESH] |Thymine Nucleotides/pharmacology[MESH]Nucleotide analogues as inhibitors of SARS-CoV Polymerase (epmc).pdf DeepDyve Pubget Overpricing