Use my Search Websuite to scan PubMed, PMCentral, Journal Hosts and Journal Archives, FullText. Kick-your-searchterm to multiple Engines kick-your-query now !>

A dictionary by aggregated review articles of nephrology, medicine and the life sciences Your one-stop-run pathway from word to the immediate pdf of peer-reviewed on-topic knowledge.

10.1016/j.compbiolchem.2020.107292 http://scihub22266oqcxt.onion/10.1016/j.compbiolchem.2020.107292 32485652!7253975!32485652     free     free     free Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 276.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 276.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 276.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 276.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 276.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 276.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Comput+Biol+Chem 2020 ; 87 (ä): 107292 Nephropedia Template TP {{tp|p=32485652|t=2020. Interaction of the prototypical alpha-ketoamide inhibitor with the SARS-CoV-2 main protease active site in silico: Molecular dynamic simulations highlight the stability of the ligand-protein complex |pdf=|usr=}}{{32485652}} gab.com Text Interaction of the prototypical alpha-ketoamide inhibitor with the SARS-CoV-2 main protease active site in silico: Molecular dynamic simulations highlight the stability of the ligand-protein complex JO: Comput Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=32485652 #FOAvip The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes an illness known as COVID-19, which has been declared a global pandemic with over 2 million confirmed cases and 137,000 deaths in 185 countries and regions at the time of writing (16 April 2020), over a quarter of these cases being in the United States. In the absence of a vaccine, or an approved effective therapeutic, there is an intense interest in repositioning available drugs or designing small molecule antivirals. In this context, in silico modelling has proven to be an invaluable tool. An important target is the SARS-CoV-2 main protease (M(pro)), involved in processing translated viral proteins. Peptidomimetic alpha-ketoamides represent prototypical inhibitors of M(pro). A recent attempt at designing a compound with enhanced pharmacokinetic properties has resulted in the synthesis and evaluation of the alpha-ketoamide 13b analogue. Here, we performed molecular docking and molecular dynamics simulations to further characterize the interaction of alpha-ketoamide 13b with the active site of the SARS-CoV-2 M(pro). We included the widely used antibiotic, amoxicillin, for comparison. Our findings indicate that alpha-ketoamide 13b binds more tightly (predicted GlideScore = -8.7 and -9.2?kcal/mol for protomers A and B, respectively), to the protease active site compared to amoxicillin (-5.0 and -4.8?kcal/mol). Further, molecular dynamics simulations highlight the stability of the interaction of the alpha-ketoamide 13b ligand with the SARS-CoV-2 M(pro) (DeltaG = -25.2 and -22.3?kcal/mol for protomers A and B). In contrast, amoxicillin interacts unfavourably with the protease (DeltaG = +32.8?kcal/mol for protomer A), with unbinding events observed in several independent simulations. Overall, our findings are consistent with those previously observed, and highlight the need to further explore the alpha-ketoamides as potential antivirals for this ongoing COVID-19 pandemic. Twit Text FOAVip Interaction of the prototypical alpha-ketoamide inhibitor with the SARS-CoV-2 main protease active site in silico: Molecular dynamic simulations highlight the stability of the ligand-protein complex ????Comput Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=32485652 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32485652 #FOAvip English Wikipedia <ref>{{Cite pmid|32485652}}</ref> Interaction of the prototypical alpha-ketoamide inhibitor with the SARS-CoV-2 main protease active site in silico: Molecular dynamic simulations highlight the stability of the ligand-protein complex #MMPMID32485652 Liang J; Pitsillou E; Karagiannis C; Darmawan KK; Ng K; Hung A; Karagiannis TC Comput Biol Chem 2020[May]; 87 (ä): 107292 PMID32485652show ga The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes an illness known as COVID-19, which has been declared a global pandemic with over 2 million confirmed cases and 137,000 deaths in 185 countries and regions at the time of writing (16 April 2020), over a quarter of these cases being in the United States. In the absence of a vaccine, or an approved effective therapeutic, there is an intense interest in repositioning available drugs or designing small molecule antivirals. In this context, in silico modelling has proven to be an invaluable tool. An important target is the SARS-CoV-2 main protease (M(pro)), involved in processing translated viral proteins. Peptidomimetic alpha-ketoamides represent prototypical inhibitors of M(pro). A recent attempt at designing a compound with enhanced pharmacokinetic properties has resulted in the synthesis and evaluation of the alpha-ketoamide 13b analogue. Here, we performed molecular docking and molecular dynamics simulations to further characterize the interaction of alpha-ketoamide 13b with the active site of the SARS-CoV-2 M(pro). We included the widely used antibiotic, amoxicillin, for comparison. Our findings indicate that alpha-ketoamide 13b binds more tightly (predicted GlideScore = -8.7 and -9.2?kcal/mol for protomers A and B, respectively), to the protease active site compared to amoxicillin (-5.0 and -4.8?kcal/mol). Further, molecular dynamics simulations highlight the stability of the interaction of the alpha-ketoamide 13b ligand with the SARS-CoV-2 M(pro) (DeltaG = -25.2 and -22.3?kcal/mol for protomers A and B). In contrast, amoxicillin interacts unfavourably with the protease (DeltaG = +32.8?kcal/mol for protomer A), with unbinding events observed in several independent simulations. Overall, our findings are consistent with those previously observed, and highlight the need to further explore the alpha-ketoamides as potential antivirals for this ongoing COVID-19 pandemic. äInteraction of the prototypical alpha-ketoamide inhibitor with the SAR(epmc).pdf DeepDyve Pubget Overpricing