Targeting the Ubiquitylation and ISGylation Machinery for the Treatment of COVID-19.

Ubiquitylation and ISGylation are protein post-translational modifications (PTMs) and two of the main events involved in the activation of pattern recognition receptor (PRRs) signals allowing the host defense response to viruses. As with similar viruses, SARS-CoV-2, the virus causing COVID-19, hijacks these pathways by removing ubiquitin and/or ISG15 from proteins using a protease called PLpro, but also by interacting with enzymes involved in ubiquitin/ISG15 machinery. These enable viral replication and avoidance of the host immune system. In this review, we highlight potential points of therapeutic intervention in ubiquitin/ISG15 pathways involved in key host-pathogen interactions, such as PLpro, USP18, TRIM25, CYLD, A20, and others that could be targeted for the treatment of COVID-19, and which may prove effective in combatting current and future vaccine-resistant variants of the disease.

Crystal structures and hydrogen-bonding analysis of a series of benzamide complexes of zinc(II) chloride.

Ionic co-crystals are co-crystals between organic mol-ecules and inorganic salt coformers. Co-crystals of pharmaceuticals are of inter-est to help control polymorph formation and potentially improve stability and other physical properties. We describe the preparation, crystal structures, and hydrogen bonding of five different 2:1 benzamide or tolu-amide/zinc(II) chloride co-crystal salts, namely, bis-(benzamide-κO)di-chlorido-zinc(II), [ZnCl2(C7H7NO)2], di-chlor-ido-bis-(2-methyl-benzamide-κO)zinc(II), [ZnCl2(C8H9NO)2], di-chlorido-bis-(3-methyl-benzamide-κO)zinc(II), [ZnCl2(C8H9NO)2], di-chlorido-bis-(4-methyl-benzamide-κO)zinc(II), [ZnCl2(C8H9NO)2], and di-chlorido-bis-(4-hy-droxy-benzamide-κO)zinc(II), [ZnCl2(C7H7NO2)2]. All of the complexes contain hydrogen bonds between the amide N-H group and the amide carbonyl oxygen atoms or the chlorine atoms, forming extended networks.