The main protease (Mpro) is a prime target for anti-SARS-CoV-2 drugs. Herein, we describe the structure-based covalent modifications that generate new nonpeptidic covalent Mpro inhibitors. The compounds exhibit strong inhibition against Mpro at submicromolar levels. The deuterated lead compound exhibits submicromolar antiviral activity against wild-type SARS-CoV-2 and Omicron variants. Biolayer interferometry analysis indicates a strong binding affinity for Mpro. The mass spectrometry results confirm the covalent bonding of the compound with the cysteine residue of Mpro. Taken together, the data may support the deuterated compound as a new lead for developing anti-SARS-CoV-2 drugs and further reveal the feasibility of using chloroacetyl for structure-based covalent drug design.
Honglei Bao, Ling-Chen Sun, Shilin Gong et al.· ACS Bio & Med Chem Au· 0 citations
In this work, red-fluorescent silver nanoclusters (MMTA@Ag NCs) with aggregation-induced emission (AIE) properties were synthesized via a facile one-pot strategy at room temperature using 2-mercapto-4-methyl-5-thiazoleacetic acid (MMTA) as the capping ligand. The as-prepared Ag NCs initially exhibited weak fluorescence in aqueous solution with a quantum yield of only 0.0037. Upon the introduction of Mn2+, the metal ions acted as electrostatic bridges by coordinating with the carboxylate groups (-COO-) on the NCs surface, triggering significant aggregation of the nanoclusters. This aggregation effectively restricted intramolecular motion, leading to a remarkable "turn-on" fluorescence enhancement with a 100-fold increase in quantum yield to 0.38. Based on this AIE mechanism, a novel fluorescent sensing platform for Mn2+ detection was established. The method exhibited a satisfactory linear response over the Mn2+ concentration range of 0.01-0.50 µmol L-1 with a low detection limit of 9.79 nmol L-1 and excellent selectivity over other interfering ions. The proposed method was successfully applied to the determination of Mn2+ in milk samples, with satisfactory recoveries ranging from 99.0% to 106.2% and RSD below 2.7%. Furthermore, a highly luminescent PVA composite film was fabricated using the MMTA@Ag NCs-Mn2+ system, demonstrating promising potential in anti-counterfeiting applications.
By moving beyond generic strategies for BBB penetration to address the distinctive pharmacotherapeutic shortcomings of depression, engineered nanomedicine holds great promise for advancing next-generation antidepressant therapies that achieve rapid onset, precise intervention, and comprehensive improvement in patient quality of life.
Mijia Zhang, En-Yao He, Y. Xiong et al.· Advanced Healthcare Material...· 0 citations
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