The emerging COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised a global catastrophe. To date, there is no specific antiviral drug available to combat this virus, except the vaccine. In this study, the main protease (M
pro
) required for SARS-CoV-2 viral replication was expressed and purified. Thirty-six compounds were tested as inhibitors of SARS-CoV-2 M
pro
by fluorescence resonance energy transfer (FRET) technique. The half-maximal inhibitory concentration (IC
50
) values of Ebselen and Ebsulfur analogs were obtained to be in the range of 0.074-0.91 μM. Notably, the molecules containing furane substituent displayed higher inhibition against M
pro
, followed by Ebselen
1i
(IC
50
= 0.074 μM) and Ebsulfur
2k
(IC
50
= 0.11 μM). The action mechanism of
1i
and
2k
were characterized by enzyme kinetics, pre-incubation and jump dilution assays, as well as fluorescent labeling experiments, which suggested that both compounds covalently and irreversibly bind to M
pro
, while molecular docking suggested that
2k
formed an S–S bond with the Cys145 at the enzymatic active site. This study provides two very potent scaffolds Ebsulfur and Ebselen for the development of covalent inhibitors of M
pro
to combat COVID-19.
In addition to conductivity, recent evidence suggests that adhesive, self-healing, and antibacterial properties are also important aspects of wearable force sensors. However, preparation of hydrogel with these combined aspects in a facile strategy is still a challenge. In this paper, a simple method is proposed to obtain adhesive, conductive, self-healing, and antibacterial chitosan−polyoxometalate (POM) hydrogel. First, silicotungstic acid (SiW) was added into a chitosan solution to form a chitosan−silicotungstic acid (CS/ SiW) physical cross-link network. Second, the CS/SiW−poly(acrylamide) (PAM) double-network hydrogels were fabricated by the in situ polymerization of acrylamide (AM). The CS/SiW-PAM hydrogel indicated excellent repeatable adhesive capacity on the surface of various materials. The CS/SiW-PAM hydrogel also displayed highly sensitive conductivity upon strain. Moreover, the CS/SiW-PAM hydrogel had outstanding self-healing and antibacterial properties. As a result, it is envisioned that the present work will broaden the path for development of POM-based functional soft materials for various applications.
We report a promising NDM-1 inhibitor, disulfiram, which can covalently bind to NDM-1 by forming an S–S bond with the Cys208 residue. Cu(DTC)2 also inactivated NDM-1 through oxidizing the Zn(ii) thiolate site of the enzyme.
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