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10.3390/ijms21093099 http://scihub22266oqcxt.onion/10.3390/ijms21093099 32353978!7247150!32353978     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       Int+J+Mol+Sci 2020 ; 21 (9): ä Nephropedia Template TP {{tp|p=32353978|t=2020. Structural and Evolutionary Analysis Indicate That the SARS-CoV-2 Mpro Is a Challenging Target for Small-Molecule Inhibitor Design |pdf=|usr=}}{{32353978}} gab.com Text Structural and Evolutionary Analysis Indicate That the SARS-CoV-2 Mpro Is a Challenging Target for Small-Molecule Inhibitor Design JO: Int J Mol Sci http://www.kidney.de/pget.php?&tw=1&pmid=32353978 #FOAvip The novel coronavirus whose outbreak took place in December 2019 continues to spread at a rapid rate worldwide. In the absence of an effective vaccine, inhibitor repurposing or de novo drug design may offer a longer-term strategy to combat this and future infections due to similar viruses. Here, we report on detailed classical and mixed-solvent molecular dynamics simulations of the main protease (Mpro) enriched by evolutionary and stability analysis of the protein. The results were compared with those for a highly similar severe acute respiratory syndrome (SARS) Mpro protein. In spite of a high level of sequence similarity, the active sites in both proteins showed major differences in both shape and size, indicating that repurposing SARS drugs for COVID-19 may be futile. Furthermore, analysis of the binding site's conformational changes during the simulation time indicated its flexibility and plasticity, which dashes hopes for rapid and reliable drug design. Conversely, structural stability of the protein with respect to flexible loop mutations indicated that the virus' mutability will pose a further challenge to the rational design of small-molecule inhibitors. However, few residues contribute significantly to the protein stability and thus can be considered as key anchoring residues for Mpro inhibitor design. Twit Text FOAVip Structural and Evolutionary Analysis Indicate That the SARS-CoV-2 Mpro Is a Challenging Target for Small-Molecule Inhibitor Design ????Int J Mol Sci http://www.kidney.de/pget.php?&tw=1&pmid=32353978 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32353978 #FOAvip English Wikipedia <ref>{{Cite pmid|32353978}}</ref> Structural and Evolutionary Analysis Indicate That the SARS-CoV-2 Mpro Is a Challenging Target for Small-Molecule Inhibitor Design #MMPMID32353978 Bzowka M; Mitusinska K; Raczynska A; Samol A; Tuszynski JA; Gora A Int J Mol Sci 2020[Apr]; 21 (9): ä PMID32353978show ga The novel coronavirus whose outbreak took place in December 2019 continues to spread at a rapid rate worldwide. In the absence of an effective vaccine, inhibitor repurposing or de novo drug design may offer a longer-term strategy to combat this and future infections due to similar viruses. Here, we report on detailed classical and mixed-solvent molecular dynamics simulations of the main protease (Mpro) enriched by evolutionary and stability analysis of the protein. The results were compared with those for a highly similar severe acute respiratory syndrome (SARS) Mpro protein. In spite of a high level of sequence similarity, the active sites in both proteins showed major differences in both shape and size, indicating that repurposing SARS drugs for COVID-19 may be futile. Furthermore, analysis of the binding site's conformational changes during the simulation time indicated its flexibility and plasticity, which dashes hopes for rapid and reliable drug design. Conversely, structural stability of the protein with respect to flexible loop mutations indicated that the virus' mutability will pose a further challenge to the rational design of small-molecule inhibitors. However, few residues contribute significantly to the protein stability and thus can be considered as key anchoring residues for Mpro inhibitor design. |*Drug Design[MESH] |*Small Molecule Libraries[MESH] |Antiviral Agents/pharmacology[MESH] |Betacoronavirus/drug effects/*enzymology/genetics[MESH] |Binding Sites[MESH] |COVID-19[MESH] |Catalytic Domain[MESH] |Coronavirus 3C Proteases[MESH] |Coronavirus Infections[MESH] |Crystallography, X-Ray[MESH] |Cysteine Endopeptidases/*chemistry/genetics[MESH] |Drug Evaluation, Preclinical[MESH] |Evolution, Molecular[MESH] |Models, Molecular[MESH] |Molecular Dynamics Simulation[MESH] |Mutation[MESH] |Pandemics[MESH] |Pneumonia, Viral[MESH] |Protease Inhibitors/*pharmacology[MESH] |SARS-CoV-2[MESH] |Severe acute respiratory syndrome-related coronavirus/enzymology[MESH] |Solvents[MESH] |Thermodynamics[MESH]Structural and Evolutionary Analysis Indicate That the SARS-CoV-2 Mpro(epmc).pdf DeepDyve Pubget Overpricing