Vaccines and therapeutics are urgently needed for the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we screen human monoclonal antibodies (mAb) targeting the receptor binding domain (RBD) of the viral spike protein via antibody library constructed from peripheral blood mononuclear cells of a convalescent patient. The CT-P59 mAb potently neutralizes SARS-CoV-2 isolates including the D614G variant without antibody-dependent enhancement effect. Complex crystal structure of CT-P59 Fab/RBD shows that CT-P59 blocks interaction regions of RBD for angiotensin converting enzyme 2 (ACE2) receptor with an orientation that is notably different from previously reported RBD-targeting mAbs. Furthermore, therapeutic effects of CT-P59 are evaluated in three animal models (ferret, hamster, and rhesus monkey), demonstrating a substantial reduction in viral titer along with alleviation of clinical symptoms. Therefore, CT-P59 may be a promising therapeutic candidate for COVID-19.

Reported herein is the metal-catalyzed regioselective C-H functionalization of quinoline N-oxides at the 8-position: direct iodination and amidation were developed using rhodium and iridium catalytic systems, respectively. Mechanistic study of the amidation revealed that the unique regioselectivity is achieved through the smooth formation of N-oxide-chelated iridacycle and that an acid additive plays a key role in the rate-determining protodemetalation step. While this approach of remote C-H activation using N-oxide as a directing group could readily be applied to a wide range of heterocyclic substrates under mild conditions with high functional group tolerance, an efficient synthesis of zinquin ester (a fluorescent zinc indicator) was demonstrated.

Background:The heterodimeric GTR GTPase is a key regulator in the amino acid mediated TORC1 pathway. Results: The structure of Gtr1p GTP -Gtr2p GDP reveals a large conformational change in comparison with that of Gtr1p GMPPNP -Gtr2p GMPPNP . Conclusion:The heterodimeric GTR GTPase serves as a novel molecular switch regulating the Raptor binding affinity. Significance: The structural information leads to a better understanding of the regulatory mechanism of the GTR GTPase.

The Rh(III)-catalyzed C-8 selective direct alkylation and alkynylation of quinoline N-oxides has been developed. The reactions proceeded highly efficiently at room temperature over a broad range of substrates with excellent regioselectivity and functional group tolerance. This development demonstrates the synthetic utility of the N-oxide directing group as a stepping stone for remote C-H functionalization of quinolines.