Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Nat+Commun 2021 ; 12 (1): 3061 Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Inhibition mechanism of SARS-CoV-2 main protease by ebselen and its derivatives #MMPMID34031399
Amporndanai K; Meng X; Shang W; Jin Z; Rogers M; Zhao Y; Rao Z; Liu ZJ; Yang H; Zhang L; O'Neill PM; Samar Hasnain S
Nat Commun 2021[May]; 12 (1): 3061 PMID34031399show ga
The SARS-CoV-2 pandemic has triggered global efforts to develop therapeutics. The main protease of SARS-CoV-2 (M(pro)), critical for viral replication, is a key target for therapeutic development. An organoselenium drug called ebselen has been demonstrated to have potent M(pro) inhibition and antiviral activity. We have examined the binding modes of ebselen and its derivative in M(pro) via high resolution co-crystallography and investigated their chemical reactivity via mass spectrometry. Stronger M(pro) inhibition than ebselen and potent ability to rescue infected cells were observed for a number of derivatives. A free selenium atom bound with cysteine of catalytic dyad has been revealed in crystallographic structures of M(pro) with ebselen and MR6-31-2 suggesting hydrolysis of the enzyme bound organoselenium covalent adduct and formation of a phenolic by-product, confirmed by mass spectrometry. The target engagement with selenation mechanism of inhibition suggests wider therapeutic applications of these compounds against SARS-CoV-2 and other zoonotic beta-corona viruses.