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10.1021/acsinfecdis.1c00070 http://scihub22266oqcxt.onion/10.1021/acsinfecdis.1c00070 33979123!8130611!33979123     free     free     free Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       ACS+Infect+Dis 2021 ; 7 (6): 1519-1534 Nephropedia Template TP {{tp|p=33979123|t=2021. Small-Molecule Inhibitors of the Coronavirus Spike: ACE2 Protein-Protein Interaction as Blockers of Viral Attachment and Entry for SARS-CoV-2 |pdf=|usr=}}{{33979123}} gab.com Text Small-Molecule Inhibitors of the Coronavirus Spike: ACE2 Protein-Protein Interaction as Blockers of Viral Attachment and Entry for SARS-CoV-2 JO: ACS Infect Dis http://www.kidney.de/pget.php?&tw=1&pmid=33979123 #FOAvip Inhibitors of the protein-protein interaction (PPI) between the SARS-CoV-2 spike protein and human ACE2 (hACE2), which acts as a ligand-receptor pair that initiates the viral attachment and cellular entry of this coronavirus causing the ongoing COVID-19 pandemic, are of considerable interest as potential antiviral agents. While blockade of such PPIs with small molecules is more challenging than that with antibodies, small-molecule inhibitors (SMIs) might offer alternatives that are less strain- and mutation-sensitive, suitable for oral or inhaled administration, and more controllable/less immunogenic. Here, we report the identification of SMIs of this PPI by screening our compound library focused around the chemical space of organic dyes. Among promising candidates identified, several dyes (Congo red, direct violet 1, Evans blue) and novel druglike compounds (DRI-C23041, DRI-C91005) inhibited the interaction of hACE2 with the spike proteins of SARS-CoV-2 as well as SARS-CoV with low micromolar activity in our cell-free ELISA-type assays (IC(50)'s of 0.2-3.0 muM), whereas control compounds, such as sunset yellow FCF, chloroquine, and suramin, showed no activity. Protein thermal shift assays indicated that the SMIs of interest identified here bind SARS-CoV-2-S and not hACE2. While dyes seemed to be promiscuous inhibitors, DRI-C23041 showed some selectivity and inhibited the entry of two different SARS-CoV-2-S expressing pseudoviruses into hACE2-expressing cells in a concentration-dependent manner with low micromolar IC(50)'s (6-7 muM). This provides proof-of-principle evidence for the feasibility of small-molecule inhibition of PPIs critical for SARS-CoV-2 attachment/entry and serves as a first guide in the search for SMI-based alternative antiviral therapies for the prevention and treatment of diseases caused by coronaviruses in general and COVID-19 in particular. Twit Text FOAVip Small-Molecule Inhibitors of the Coronavirus Spike: ACE2 Protein-Protein Interaction as Blockers of Viral Attachment and Entry for SARS-CoV-2 ????ACS Infect Dis http://www.kidney.de/pget.php?&tw=1&pmid=33979123 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33979123 #FOAvip English Wikipedia <ref>{{Cite pmid|33979123}}</ref> Small-Molecule Inhibitors of the Coronavirus Spike: ACE2 Protein-Protein Interaction as Blockers of Viral Attachment and Entry for SARS-CoV-2 #MMPMID33979123 Bojadzic D; Alcazar O; Chen J; Chuang ST; Condor Capcha JM; Shehadeh LA; Buchwald P ACS Infect Dis 2021[Jun]; 7 (6): 1519-1534 PMID33979123show ga Inhibitors of the protein-protein interaction (PPI) between the SARS-CoV-2 spike protein and human ACE2 (hACE2), which acts as a ligand-receptor pair that initiates the viral attachment and cellular entry of this coronavirus causing the ongoing COVID-19 pandemic, are of considerable interest as potential antiviral agents. While blockade of such PPIs with small molecules is more challenging than that with antibodies, small-molecule inhibitors (SMIs) might offer alternatives that are less strain- and mutation-sensitive, suitable for oral or inhaled administration, and more controllable/less immunogenic. Here, we report the identification of SMIs of this PPI by screening our compound library focused around the chemical space of organic dyes. Among promising candidates identified, several dyes (Congo red, direct violet 1, Evans blue) and novel druglike compounds (DRI-C23041, DRI-C91005) inhibited the interaction of hACE2 with the spike proteins of SARS-CoV-2 as well as SARS-CoV with low micromolar activity in our cell-free ELISA-type assays (IC(50)'s of 0.2-3.0 muM), whereas control compounds, such as sunset yellow FCF, chloroquine, and suramin, showed no activity. Protein thermal shift assays indicated that the SMIs of interest identified here bind SARS-CoV-2-S and not hACE2. While dyes seemed to be promiscuous inhibitors, DRI-C23041 showed some selectivity and inhibited the entry of two different SARS-CoV-2-S expressing pseudoviruses into hACE2-expressing cells in a concentration-dependent manner with low micromolar IC(50)'s (6-7 muM). This provides proof-of-principle evidence for the feasibility of small-molecule inhibition of PPIs critical for SARS-CoV-2 attachment/entry and serves as a first guide in the search for SMI-based alternative antiviral therapies for the prevention and treatment of diseases caused by coronaviruses in general and COVID-19 in particular. |*Virus Attachment/drug effects[MESH] |Angiotensin-Converting Enzyme 2/*metabolism[MESH] |COVID-19/prevention & control[MESH] |Humans[MESH] |Pandemics[MESH] |Protein Interaction Domains and Motifs[MESH] |SARS-CoV-2/*drug effects[MESH]Small-Molecule Inhibitors of the Coronavirus Spike: ACE2 Protein-Prote(epmc).pdf DeepDyve Pubget Overpricing