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We report molecular interactions and inhibition of the main protease (MPro) of SARS-CoV-2, a key enzyme involved in the viral life cycle. By using a thiadiazolidinone (TDZD) derivative as a chemical probe, we explore the conformational dynamics of MPro via docking protocols and molecular dynamics simulations in all-atom detail. We reveal the local and global dynamics of MPro in the presence of this inhibitor and confirm the inhibition of the enzyme with an IC50 value of 1.39 ± 0.22 μM, which is comparable to other known inhibitors of this enzyme. 

Post-synthetic phase transfer ligand exchange has been established as a simple, reliable, and versatile method for the synthesis of chiral, optically active colloidal nanocrystals displaying circular dichroism (CD) and circularly polarized luminescence (CPL). Herein we present a water-free and purification-free cyclohexane → methanol ligand exchange system that led to the synthesis of stable, non-aggregating chiral and fluorescent cadmium sulfide quantum dots (CdS QDs). Absorption and emission studies revealed that the carboxylate capping ligands can tune the band gap by up to 65 meV as well as control the band gap and deep trap emission pathways. The CD data revealed that the addition of a 2nd stereogenic center did not automatically lead to an increase of the CD anisotropy of QDs, but rather match/mismatch cooperativity effects must be considered in the transfer of the chirality from the capping ligands to the achiral nanocrystals. Variation in position of the functional groups as well as the chemical identity of the functional groups impacted both the shape and anisotropy of the induced CD spectra and revealed the importance of the functional groups’ coordination and polarity on the binding geometry and induced chiroptical properties. Finally, we describe the first example where CD spectra of QDs capped with the same ligand and dissolved in the same solvent displayed very different spectral profiles. This work provides deeper insight into induced CD of QDs and paves the path to rational design of chiral nanomaterials. 

The highly infectious disease COVID-19 caused by the Betacoronavirus SARS-CoV-2 poses a severe threat to humanity and demands the redirection of scientific efforts and criteria to organized research projects. The international COVID19-NMR consortium seeks to provide such new approaches by gathering scientific expertise worldwide. In particular, making available viral proteins and RNAs will pave the way to understanding the SARS-CoV-2 molecular components in detail. The research in COVID19-NMR and the resources provided through the consortium are fully disclosed to accelerate access and exploitation. NMR investigations of the viral molecular components are designated to provide the essential basis for further work, including macromolecular interaction studies and high-throughput drug screening. Here, we present the extensive catalog of a holistic SARS-CoV-2 protein preparation approach based on the consortium’s collective efforts. We provide protocols for the large-scale production of more than 80% of all SARS-CoV-2 proteins or essential parts of them. Several of the proteins were produced in more than one laboratory, demonstrating the high interoperability between NMR groups worldwide. For the majority of proteins, we can produce isotope-labeled samples of HSQC-grade. Together with several NMR chemical shift assignments made publicly available on covid19-nmr.com , we here provide highly valuable resources for the production of SARS-CoV-2 proteins in isotope-labeled form.