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10.3389/fphar.2020.01091 http://scihub22266oqcxt.onion/10.3389/fphar.2020.01091 32792942!7385287!32792942     free     free     free Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 284.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 284.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 284.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Front+Pharmacol 2020 ; 11 (ä): 1091 Nephropedia Template TP {{tp|p=32792942|t=2020. Evidence for the Effectiveness of Remdesivir (GS-5734), a Nucleoside-Analog Antiviral Drug in the Inhibition of I (K(M)) or I (K(DR)) and in the Stimulation of I (MEP) |pdf=|usr=}}{{32792942}} gab.com Text Evidence for the Effectiveness of Remdesivir (GS-5734), a Nucleoside-Analog Antiviral Drug in the Inhibition of I (K(M)) or I (K(DR)) and in the Stimulation of I (MEP) JO: Front Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=32792942 #FOAvip Remdesivir (RDV, GS-5734), a broad-spectrum antiviral drug in the class of nucleotide analogs, has been particularly tailored for treatment of coronavirus infections. However, to which extent RDV is able to modify various types of membrane ion currents remains largely uncertain. In this study, we hence intended to explore the possible perturbations of RDV on ionic currents endogenous in pituitary GH(3) cells and Jurkat T-lymphocytes. The whole-cell current recordings of ours disclosed that upon membrane depolarization in GH(3) cells the exposure to RDV concentration-dependently depressed the peak or late components of I (K(DR)) elicitation with effective IC(50) values of 10.1 or 2.8 muM, respectively; meanwhile, the value of dissociation constant of RDV-induced blockage of I (K(DR)) on the basis of the first-order reaction was yielded to be 3.04 muM. Upon the existence of RDV, the steady-state inactivation curve of I (K(DR)) was established in the RDV presence; moreover, the recovery became slowed. However, RDV-induced blockage of I (K(DR)) failed to be overcome by further addition of either alpha,beta-methylene ATP or cyclopentyl-1,3-dipropylxanthine. The RDV addition also lessened the strength of M-type K(+) current with the IC(50) value of 2.5 muM. The magnitude of voltage hysteresis of I (K(M)) elicited by long-lasting triangular ramp pulse was diminished by adding RDV. Membrane electroporation-induced current in response to large hyperpolarization was enhanced, with an EC(50) value of 5.8 muM. Likewise, in Jurkat T-lymphocytes, adding RDV declined I (K(DR)) amplitude concomitantly with the raised rate of current inactivation applied by step depolarization. Therefore, in terms of the RDV molecule, there appears to be an unintended activity of the prodrug on ion channels. Its inhibition of both I (K(DR)) and I (K(M)) occurring in a non-genomic fashion might provide additional but important mechanisms through which in vivo cellular functions are seriously perturbed. Twit Text FOAVip Evidence for the Effectiveness of Remdesivir (GS-5734), a Nucleoside-Analog Antiviral Drug in the Inhibition of I (K(M)) or I (K(DR)) and in the Stimulation of I (MEP) ????Front Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=32792942 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32792942 #FOAvip English Wikipedia <ref>{{Cite pmid|32792942}}</ref> Evidence for the Effectiveness of Remdesivir (GS-5734), a Nucleoside-Analog Antiviral Drug in the Inhibition of I (K(M)) or I (K(DR)) and in the Stimulation of I (MEP) #MMPMID32792942 Chang WT; Liu PY; Gao ZH; Lee SW; Lee WK; Wu SN Front Pharmacol 2020[]; 11 (ä): 1091 PMID32792942show ga Remdesivir (RDV, GS-5734), a broad-spectrum antiviral drug in the class of nucleotide analogs, has been particularly tailored for treatment of coronavirus infections. However, to which extent RDV is able to modify various types of membrane ion currents remains largely uncertain. In this study, we hence intended to explore the possible perturbations of RDV on ionic currents endogenous in pituitary GH(3) cells and Jurkat T-lymphocytes. The whole-cell current recordings of ours disclosed that upon membrane depolarization in GH(3) cells the exposure to RDV concentration-dependently depressed the peak or late components of I (K(DR)) elicitation with effective IC(50) values of 10.1 or 2.8 muM, respectively; meanwhile, the value of dissociation constant of RDV-induced blockage of I (K(DR)) on the basis of the first-order reaction was yielded to be 3.04 muM. Upon the existence of RDV, the steady-state inactivation curve of I (K(DR)) was established in the RDV presence; moreover, the recovery became slowed. However, RDV-induced blockage of I (K(DR)) failed to be overcome by further addition of either alpha,beta-methylene ATP or cyclopentyl-1,3-dipropylxanthine. The RDV addition also lessened the strength of M-type K(+) current with the IC(50) value of 2.5 muM. The magnitude of voltage hysteresis of I (K(M)) elicited by long-lasting triangular ramp pulse was diminished by adding RDV. Membrane electroporation-induced current in response to large hyperpolarization was enhanced, with an EC(50) value of 5.8 muM. Likewise, in Jurkat T-lymphocytes, adding RDV declined I (K(DR)) amplitude concomitantly with the raised rate of current inactivation applied by step depolarization. Therefore, in terms of the RDV molecule, there appears to be an unintended activity of the prodrug on ion channels. Its inhibition of both I (K(DR)) and I (K(M)) occurring in a non-genomic fashion might provide additional but important mechanisms through which in vivo cellular functions are seriously perturbed. äEvidence for the Effectiveness of Remdesivir (GS-5734), a Nucleoside-A(epmc).pdf DeepDyve Pubget Overpricing