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10.1016/j.bioorg.2021.105196 http://scihub22266oqcxt.onion/10.1016/j.bioorg.2021.105196 34333425!8318836!34333425     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Bioorg+Chem 2021 ; 115 (ä): 105196 Nephropedia Template TP {{tp|p=34333425|t=2021. Discovery and evolution of 12N-substituted aloperine derivatives as anti-SARS-CoV-2 agents through targeting late entry stage |pdf=|usr=}}{{34333425}} gab.com Text Discovery and evolution of 12N-substituted aloperine derivatives as anti-SARS-CoV-2 agents through targeting late entry stage JO: Bioorg Chem http://www.kidney.de/pget.php?&tw=1&pmid=34333425 #FOAvip So far, there is still no specific drug against COVID-19. Taking compound 1 with anti-EBOV activity as the lead, fifty-four 12N-substituted aloperine derivatives were synthesized and evaluated for the anti-SARS-CoV-2 activities using pseudotyped virus model. Among them, 8a exhibited the most potential effects against both pseudotyped and authentic SARS-CoV-2, as well as SARS-CoV and MERS-CoV, indicating a broad-spectrum anti-coronavirus profile. The mechanism study disclosed that 8a might block a late stage of viral entry, mainly via inhibiting host cathepsin B activity rather than directly targeting cathepsin B protein. Also, 8a could significantly reduce the release of multiple inflammatory cytokines in a time- and dose-dependent manner, such as IL-6, IL-1beta, IL-8 and MCP-1, the major contributors to cytokine storm. Therefore, 8a is a promising agent with the advantages of broad-spectrum anti-coronavirus and anti-cytokine effects, thus worthy of further investigation. Twit Text FOAVip Discovery and evolution of 12N-substituted aloperine derivatives as anti-SARS-CoV-2 agents through targeting late entry stage ????Bioorg Chem http://www.kidney.de/pget.php?&tw=1&pmid=34333425 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34333425 #FOAvip English Wikipedia <ref>{{Cite pmid|34333425}}</ref> Discovery and evolution of 12N-substituted aloperine derivatives as anti-SARS-CoV-2 agents through targeting late entry stage #MMPMID34333425 Wang K; Wu JJ; Xin-Zhang; Zeng QX; Zhang N; Huang WJ; Tang S; Wang YX; Kong WJ; Wang YC; Li YH; Song DQ Bioorg Chem 2021[Oct]; 115 (ä): 105196 PMID34333425show ga So far, there is still no specific drug against COVID-19. Taking compound 1 with anti-EBOV activity as the lead, fifty-four 12N-substituted aloperine derivatives were synthesized and evaluated for the anti-SARS-CoV-2 activities using pseudotyped virus model. Among them, 8a exhibited the most potential effects against both pseudotyped and authentic SARS-CoV-2, as well as SARS-CoV and MERS-CoV, indicating a broad-spectrum anti-coronavirus profile. The mechanism study disclosed that 8a might block a late stage of viral entry, mainly via inhibiting host cathepsin B activity rather than directly targeting cathepsin B protein. Also, 8a could significantly reduce the release of multiple inflammatory cytokines in a time- and dose-dependent manner, such as IL-6, IL-1beta, IL-8 and MCP-1, the major contributors to cytokine storm. Therefore, 8a is a promising agent with the advantages of broad-spectrum anti-coronavirus and anti-cytokine effects, thus worthy of further investigation. |Animals[MESH] |Antiviral Agents/chemical synthesis/pharmacokinetics/*pharmacology/toxicity[MESH] |Cathepsin B/antagonists & inhibitors[MESH] |Chlorocebus aethiops[MESH] |Cytokines/metabolism[MESH] |HEK293 Cells[MESH] |Humans[MESH] |Male[MESH] |Mice[MESH] |Microbial Sensitivity Tests[MESH] |Molecular Structure[MESH] |Piperidines/chemical synthesis/pharmacokinetics/*pharmacology/toxicity[MESH] |Quinolizidines/chemical synthesis/pharmacokinetics/*pharmacology/toxicity[MESH] |Rats[MESH] |Rats, Sprague-Dawley[MESH] |SARS-CoV-2/*drug effects[MESH] |Structure-Activity Relationship[MESH] |Vero Cells[MESH]Discovery and evolution of 12N-substituted aloperine derivatives as a(epmc).pdf DeepDyve Pubget Overpricing