Acid pro 7 completo
SARS-CoV-2 is the most devastating zoonotic coronavirus to infect humans following SARS-CoV-1 and MERS-CoV (Middle East respiratory syndrome) which emerged in 20, respectively 1. The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a global pandemic of coronavirus disease 2019 (COVID-19) with confirmed infection cases of over 140 million and 3 million fatalities as of April 2021. 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.
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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. Stronger M pro inhibition than ebselen and potent ability to rescue infected cells were observed for a number of derivatives. 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. An organoselenium drug called ebselen has been demonstrated to have potent M pro inhibition and antiviral activity. The main protease of SARS-CoV-2 (M pro), critical for viral replication, is a key target for therapeutic development. The SARS-CoV-2 pandemic has triggered global efforts to develop therapeutics.