Biological characterization of AB-343, a novel and potent SARS-CoV-2 M inhibitor with pan-coronavirus activity.

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.

Rational Design of Macrocyclic Noncovalent Inhibitors of SARS-CoV-2 M from a DNA-Encoded Chemical Library Screening Hit That Demonstrate Potent Inhibition against Pan-Coronavirus Homologues and Nirmatrelvir-Resistant Variants.

The recent global COVID-19 pandemic has highlighted treatments for coronavirus infection as an unmet medical need. The main protease (M) has been an important target for the development of SARS-CoV-2 direct-acting antivirals. Nirmatrelvir as a covalent M inhibitor was the first such approved therapy.

Strategies and Tactics for Site Specific Deuterium Incorporation at Each Available Carbon Atom of α-Pinene.

The development of several unique strategies and tactics for the synthesis of α-pinene isotopologues that has culminated in access to all eight possible isomers with deuterium incorporated selectively at each available carbon atom is described. Access to this library of isotopologues provides new tools to more fully investigate the atmospheric autoxidation of α-pinene, a complex process that plays a major role in the formation of secondary organic aerosol in the Earth's atmosphere.

Genome Mining and Metabolomics Uncover a Rare d-Capreomycidine Containing Natural Product and Its Biosynthetic Gene Cluster.

We report the metabolomics-driven genome mining of a new cyclic-guanidino incorporating non-ribosomal peptide synthetase (NRPS) gene cluster and full structure elucidation of its associated hexapeptide product, faulknamycin. Structural studies unveiled that this natural product contained the previously unknown (,)-stereoisomer of capreomycidine, d-capreomycidine. Furthermore, heterologous expression of the identified gene cluster successfully reproduces faulknamycin production without an observed homologue of VioD, the pyridoxal phosphate (PLP)-dependent enzyme found in all previous l-capreomycidine biosynthesis.

Ion Mobility Mass Spectrometry as an Efficient Tool for Identification of Streptorubin B in M145.

Ion mobility spectrometry was utilized to corroborate the identity of streptorubin B () as the natural product produced by . Natural product was initially assigned as butylcycloheptylprodigiosin (), and only relatively recently was this assignment clarified. We present additional evidence of this assignment by comparing collisional cross sections (Ω) of synthetic standards of , , and metacycloprodigiosin () to the cyclic prodiginine produced by .

Synthesis and surface spectroscopy of α-pinene isotopologues and their corresponding secondary organic material.

Atmospheric aerosol-cloud interactions remain among the least understood processes within the climate system, leaving large uncertainties in the prediction of future climates. In particular, the nature of the surfaces of aerosol particles formed from biogenic terpenes, such as α-pinene, is poorly understood despite the importance of surface phenomena in their formation, growth, radiative properties, and ultimate fate. Herein we report the coupling of a site-specific deuterium labeling strategy with vibrational sum frequency generation (SFG) spectroscopy to probe the surface C-H oscillators in α-pinene-derived secondary organic aerosol material (SOM) generated in an atmospheric flow tube reactor.

Structure-Activity Relationship-based Optimization of Small Temporin-SHf Analogs with Potent Antibacterial Activity.

Short antimicrobial peptides represent attractive compounds for the development of new antibiotic agents. Previously, we identified an ultrashort hydrophobic and phenylalanine-rich peptide, called temporin-SHf, representing the smallest natural amphibian antimicrobial peptide known to date. Here, we report on the first structure-activity relationship study of this peptide.

Enantioselective synthesis of metacycloprodigiosin via the "Wasserman pyrrole".

A concise, nine-step enantioselective total synthesis of metacycloprodigiosin is reported. The synthesis provides increased step-efficiency over the previous racemic and enantioselective syntheses of this compound. Key features of the work include investigations into a convergent oxidative coupling reaction and subsequent ring-closing metathesis to deliver an advanced pyrrole intermediate we name the "Wasserman pyrrole" that can be converted to metacycloprodigiosin in one step.