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10.15252/emmm.202013426 http://scihub22266oqcxt.onion/10.15252/emmm.202013426 33179852!7799356!33179852     free     free     free Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       EMBO+Mol+Med 2021 ; 13 (1): e13426 Nephropedia Template TP {{tp|p=33179852|t=2021. Human soluble ACE2 improves the effect of remdesivir in SARS-CoV-2 infection |pdf=|usr=}}{{33179852}} gab.com Text Human soluble ACE2 improves the effect of remdesivir in SARS-CoV-2 infection JO: EMBO Mol Med http://www.kidney.de/pget.php?&tw=1&pmid=33179852 #FOAvip There is a critical need for safe and effective drugs for COVID-19. Only remdesivir has received authorization for COVID-19 and has been shown to improve outcomes but not decrease mortality. However, the dose of remdesivir is limited by hepatic and kidney toxicity. ACE2 is the critical cell surface receptor for SARS-CoV-2. Here, we investigated additive effect of combination therapy using remdesivir with recombinant soluble ACE2 (high/low dose) on Vero E6 and kidney organoids, targeting two different modalities of SARS-CoV-2 life cycle: cell entry via its receptor ACE2 and intracellular viral RNA replication. This combination treatment markedly improved their therapeutic windows against SARS-CoV-2 in both models. By using single amino-acid resolution screening in haploid ES cells, we report a singular critical pathway required for remdesivir toxicity, namely, Adenylate Kinase 2. The data provided here demonstrate that combining two therapeutic modalities with different targets, common strategy in HIV treatment, exhibit strong additive effects at sub-toxic concentrations. Our data lay the groundwork for the study of combinatorial regimens in future COVID-19 clinical trials. Twit Text FOAVip Human soluble ACE2 improves the effect of remdesivir in SARS-CoV-2 infection ????EMBO Mol Med http://www.kidney.de/pget.php?&tw=1&pmid=33179852 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33179852 #FOAvip English Wikipedia <ref>{{Cite pmid|33179852}}</ref> Human soluble ACE2 improves the effect of remdesivir in SARS-CoV-2 infection #MMPMID33179852 Monteil V; Dyczynski M; Lauschke VM; Kwon H; Wirnsberger G; Youhanna S; Zhang H; Slutsky AS; Hurtado Del Pozo C; Horn M; Montserrat N; Penninger JM; Mirazimi A EMBO Mol Med 2021[Jan]; 13 (1): e13426 PMID33179852show ga There is a critical need for safe and effective drugs for COVID-19. Only remdesivir has received authorization for COVID-19 and has been shown to improve outcomes but not decrease mortality. However, the dose of remdesivir is limited by hepatic and kidney toxicity. ACE2 is the critical cell surface receptor for SARS-CoV-2. Here, we investigated additive effect of combination therapy using remdesivir with recombinant soluble ACE2 (high/low dose) on Vero E6 and kidney organoids, targeting two different modalities of SARS-CoV-2 life cycle: cell entry via its receptor ACE2 and intracellular viral RNA replication. This combination treatment markedly improved their therapeutic windows against SARS-CoV-2 in both models. By using single amino-acid resolution screening in haploid ES cells, we report a singular critical pathway required for remdesivir toxicity, namely, Adenylate Kinase 2. The data provided here demonstrate that combining two therapeutic modalities with different targets, common strategy in HIV treatment, exhibit strong additive effects at sub-toxic concentrations. Our data lay the groundwork for the study of combinatorial regimens in future COVID-19 clinical trials. |*COVID-19 Drug Treatment[MESH] |Adenosine Monophosphate/*analogs & derivatives/pharmacology[MESH] |Alanine/*analogs & derivatives/pharmacology[MESH] |Angiotensin-Converting Enzyme 2/*pharmacology[MESH] |Animals[MESH] |Antiviral Agents/*pharmacology[MESH] |Cells, Cultured[MESH] |Chlorocebus aethiops[MESH] |Drug Synergism[MESH] |Humans[MESH] |Models, Molecular[MESH] |Recombinant Proteins/pharmacology[MESH] |SARS-CoV-2/*drug effects/physiology[MESH] |Vero Cells[MESH] |Virus Internalization/drug effects[MESH]Human soluble ACE2 improves the effect of remdesivir in SARS-CoV-2 inf(epmc).pdf DeepDyve Pubget Overpricing