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10.1073/pnas.2111172118 http://scihub22266oqcxt.onion/10.1073/pnas.2111172118 34426525!8433497!34426525     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       Proc+Natl+Acad+Sci+U+S+A 2021 ; 118 (36): ä Nephropedia Template TP {{tp|p=34426525|t=2021. DNA-encoded chemistry technology yields expedient access to SARS-CoV-2 M(pro) inhibitors |pdf=|usr=}}{{34426525}} gab.com Text DNA-encoded chemistry technology yields expedient access to SARS-CoV-2 M(pro) inhibitors JO: Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=34426525 #FOAvip Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed more than 4 million humans globally, but there is no bona fide Food and Drug Administration-approved drug-like molecule to impede the COVID-19 pandemic. The sluggish pace of traditional therapeutic discovery is poorly suited to producing targeted treatments against rapidly evolving viruses. Here, we used an affinity-based screen of 4 billion DNA-encoded molecules en masse to identify a potent class of virus-specific inhibitors of the SARS-CoV-2 main protease (M(pro)) without extensive and time-consuming medicinal chemistry. CDD-1714, the initial three-building-block screening hit (molecular weight [MW] = 542.5 g/mol), was a potent inhibitor (inhibition constant [K(i)] = 20 nM). CDD-1713, a smaller two-building-block analog (MW = 353.3 g/mol) of CDD-1714, is a reversible covalent inhibitor of M(pro) (K(i) = 45 nM) that binds in the protease pocket, has specificity over human proteases, and shows in vitro efficacy in a SARS-CoV-2 infectivity model. Subsequently, key regions of CDD-1713 that were necessary for inhibitory activity were identified and a potent (K(i) = 37 nM), smaller (MW = 323.4 g/mol), and metabolically more stable analog (CDD-1976) was generated. Thus, screening of DNA-encoded chemical libraries can accelerate the discovery of efficacious drug-like inhibitors of emerging viral disease targets. Twit Text FOAVip DNA-encoded chemistry technology yields expedient access to SARS-CoV-2 M(pro) inhibitors ????Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=34426525 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34426525 #FOAvip English Wikipedia <ref>{{Cite pmid|34426525}}</ref> DNA-encoded chemistry technology yields expedient access to SARS-CoV-2 M(pro) inhibitors #MMPMID34426525 Chamakuri S; Lu S; Ucisik MN; Bohren KM; Chen YC; Du HC; Faver JC; Jimmidi R; Li F; Li JY; Nyshadham P; Palmer SS; Pollet J; Qin X; Ronca SE; Sankaran B; Sharma KL; Tan Z; Versteeg L; Yu Z; Matzuk MM; Palzkill T; Young DW Proc Natl Acad Sci U S A 2021[Sep]; 118 (36): ä PMID34426525show ga Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed more than 4 million humans globally, but there is no bona fide Food and Drug Administration-approved drug-like molecule to impede the COVID-19 pandemic. The sluggish pace of traditional therapeutic discovery is poorly suited to producing targeted treatments against rapidly evolving viruses. Here, we used an affinity-based screen of 4 billion DNA-encoded molecules en masse to identify a potent class of virus-specific inhibitors of the SARS-CoV-2 main protease (M(pro)) without extensive and time-consuming medicinal chemistry. CDD-1714, the initial three-building-block screening hit (molecular weight [MW] = 542.5 g/mol), was a potent inhibitor (inhibition constant [K(i)] = 20 nM). CDD-1713, a smaller two-building-block analog (MW = 353.3 g/mol) of CDD-1714, is a reversible covalent inhibitor of M(pro) (K(i) = 45 nM) that binds in the protease pocket, has specificity over human proteases, and shows in vitro efficacy in a SARS-CoV-2 infectivity model. Subsequently, key regions of CDD-1713 that were necessary for inhibitory activity were identified and a potent (K(i) = 37 nM), smaller (MW = 323.4 g/mol), and metabolically more stable analog (CDD-1976) was generated. Thus, screening of DNA-encoded chemical libraries can accelerate the discovery of efficacious drug-like inhibitors of emerging viral disease targets. |Animals[MESH] |COVID-19 Drug Treatment[MESH] |COVID-19/virology[MESH] |Cells, Cultured[MESH] |Coronavirus 3C Proteases/*antagonists & inhibitors/*genetics/metabolism[MESH] |Dose-Response Relationship, Drug[MESH] |Drug Discovery/*methods[MESH] |Enzyme Activation[MESH] |Genetic Engineering[MESH] |Humans[MESH] |Models, Molecular[MESH] |Molecular Conformation[MESH] |Molecular Structure[MESH] |Protease Inhibitors/*chemistry/*pharmacology[MESH] |SARS-CoV-2/*drug effects/*genetics/metabolism[MESH] |Structure-Activity Relationship[MESH]DNA-encoded chemistry technology yields expedient access to SARS-CoV-2(epmc).pdf DeepDyve Pubget Overpricing