9GLV

Crystal structure of SARS-CoV-2 Mpro with AB-343.

これはPDB形式変換不可エントリーです。

9GLV の概要

• エントリーDOI: 10.2210/pdb9glv/pdb
• 分子名称: 3C-like proteinase nsp5, (1S,3S,4S)-N-[(2S)-1-azanylidene-3-[(3S)-5,5-dimethyl-2-oxidanylidene-pyrrolidin-3-yl]propan-2-yl]-2-[(2R)-3-cyclobutyl-2-[2,2,2-tris(fluoranyl)ethanoylamino]propanoyl]-5,5-bis(fluoranyl)-2-azabicyclo[2.2.2]octane-3-carboxamide, CHLORIDE ION, ... (6 entities in total)
• 機能のキーワード: protein, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 69178.10

構造登録者

Prasad, A.,Blaesse, M.,Maskos, K.,Steinbacher, S.,Konz Makino, D.L. (登録日: 2024-08-28, 公開日: 2024-12-04, 最終更新日: 2024-12-11)

主引用文献

McGovern-Gooch, K.R.,Mani, N.,Gotchev, D.,Ardzinski, A.,Kowalski, R.,Sheraz, M.,Micolochick Steuer, H.M.,Tercero, B.,Wang, X.,Wasserman, A.,Chen, C.Y.,von Konig, K.,Maskos, K.,Prasad, A.,Blaesse, M.,Bergmann, A.,Konz Makino, D.L.,Fan, K.Y.,Kultgen, S.G.,Lindstrom, A.,Nguyen, D.,Vega, M.,Wang, X.,Bracci, N.,Weiss, S.R.,Cole, A.G.,Lam, A.M.,Cuconati, A.,Sofia, M.J.
Biological characterization of AB-343, a novel and potent SARS-CoV-2 M pro inhibitor with pan-coronavirus activity.
Antiviral Res., 232:106038-106038, 2024

PubMed Abstract: Since the SARS-CoV-2 outbreak, there have been ongoing efforts to identify antiviral molecules with broad coronavirus activity to combat COVID-19. SARS-CoV-2's main protease (M) is responsible for processing the viral polypeptide into non-structural proteins essential for replication. Here, we present the biological characterization of AB-343, a covalent small-molecule inhibitor of SARS-CoV-2 M with potent activity in both cell-based (EC = 0.018 μM) and enzymatic (K = 0.0028 μM) assays. AB-343 also demonstrated excellent inhibition of M of other human coronaviruses, including those from the alpha (229E and NL63) and beta (SARS-CoV, MERS, OC43, and HKU1) families, suggesting the compound could be active against future coronaviruses. No change in AB-343 potency was observed against M of SARS-CoV-2 variants of concern, including Omicron, suggesting that AB-343 could be developed as a treatment against currently circulating coronaviruses. AB-343 also remained active against several M variants which confer significant resistance to nirmatrelvir and ensitrelvir, which are presently the only M inhibitors authorized for the treatment of COVID-19, further supporting the evaluation of AB-343 as a novel and potent therapeutic for COVID-19 and other coronaviruses.

PubMed: 39577571
DOI: 10.1016/j.antiviral.2024.106038

実験手法

X-RAY DIFFRACTION (1.93 Å)