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.

10.1002/iub.2465 http://scihub22266oqcxt.onion/10.1002/iub.2465 33749986!8250577!33749986     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       IUBMB+Life 2021 ; 73 (4): 670-675 Nephropedia Template TP {{tp|p=33749986|t=2021. Identification of mutation resistance coldspots for targeting the SARS-CoV2 main protease |pdf=|usr=}}{{33749986}} gab.com Text Identification of mutation resistance coldspots for targeting the SARS-CoV2 main protease JO: IUBMB Life http://www.kidney.de/pget.php?&tw=1&pmid=33749986 #FOAvip Mutations in the novel coronavirus SARS-CoV2 are the major concern as they might lead to drug/vaccine resistance. In the host cell, the virus largely depends on the main protease (M(pro) ) to regulate infection hence it is one of the most attractive targets for inhibitor design. However, >19,000 mutations in the M(pro) have already been reported. The mutations encompassing 282 amino acid positions and these "hotspots" might change the M(pro) structure, activity and potentially delay therapeutic strategies targeting M(pro) . Thus, here we identified 24 mutational "coldspots" where mutations have not been observed. We compared the structure-function relationship of these coldspots with several SARS-CoV2 M(pro) X-ray crystal structures. We found that three coldspot residues (Leu141, Phe185, and Gln192) help to form the active site, while seven (Gly2, Arg4, Tyr126, Lys137, Leu141, Leu286, and Leu287) contribute to dimer formation that is required for M(pro) activity. The surface of the dimer interface is more resistant to mutations compared to the active site. Interestingly, most of the coldspots are found in three clusters and forms conserved patterns when compared with other coronaviruses. Importantly, several conserved coldspots are available on the surface of the active site and at the dimer interface for targeting. The identification and short list of these coldspots offers a new perspective to target the SARS-CoV2 M(pro) while avoiding mutation-based drug resistance. Twit Text FOAVip Identification of mutation resistance coldspots for targeting the SARS-CoV2 main protease ????IUBMB Life http://www.kidney.de/pget.php?&tw=1&pmid=33749986 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33749986 #FOAvip English Wikipedia <ref>{{Cite pmid|33749986}}</ref> Identification of mutation resistance coldspots for targeting the SARS-CoV2 main protease #MMPMID33749986 Krishnamoorthy N; Fakhro K IUBMB Life 2021[Apr]; 73 (4): 670-675 PMID33749986show ga Mutations in the novel coronavirus SARS-CoV2 are the major concern as they might lead to drug/vaccine resistance. In the host cell, the virus largely depends on the main protease (M(pro) ) to regulate infection hence it is one of the most attractive targets for inhibitor design. However, >19,000 mutations in the M(pro) have already been reported. The mutations encompassing 282 amino acid positions and these "hotspots" might change the M(pro) structure, activity and potentially delay therapeutic strategies targeting M(pro) . Thus, here we identified 24 mutational "coldspots" where mutations have not been observed. We compared the structure-function relationship of these coldspots with several SARS-CoV2 M(pro) X-ray crystal structures. We found that three coldspot residues (Leu141, Phe185, and Gln192) help to form the active site, while seven (Gly2, Arg4, Tyr126, Lys137, Leu141, Leu286, and Leu287) contribute to dimer formation that is required for M(pro) activity. The surface of the dimer interface is more resistant to mutations compared to the active site. Interestingly, most of the coldspots are found in three clusters and forms conserved patterns when compared with other coronaviruses. Importantly, several conserved coldspots are available on the surface of the active site and at the dimer interface for targeting. The identification and short list of these coldspots offers a new perspective to target the SARS-CoV2 M(pro) while avoiding mutation-based drug resistance. |*Mutation[MESH] |Antiviral Agents/pharmacology[MESH] |COVID-19/*metabolism/virology[MESH] |Coronavirus 3C Proteases/chemistry/*genetics[MESH] |Crystallography, X-Ray[MESH] |Humans[MESH] |Protein Conformation[MESH]Identification of mutation resistance coldspots for targeting the SARS(epmc).pdf DeepDyve Pubget Overpricing