Pathophysiological mechanisms of liver injury in COVID-19

The recent outbreak of coronavirus disease 2019 (COVID‐19), caused by the Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) has resulted in a world‐wide pandemic. Disseminated lung injury with the development of acute respiratory distress syndrome (ARDS) is the main cause of mortality in COVID‐19. Although liver failure does not seem to occur in the absence of pre‐existing liver disease, hepatic involvement in COVID‐19 may correlate with overall disease severity and serve as a prognostic factor for the development of ARDS. The spectrum of liver injury in COVID‐19 may range from direct infection by SARS‐CoV‐2, indirect involvement by systemic inflammation, hypoxic changes, iatrogenic causes such as drugs and ventilation to exacerbation of underlying liver disease. This concise review discusses the potential pathophysiological mechanisms for SARS‐CoV‐2 hepatic tropism as well as acute and possibly long‐term liver injury in COVID‐19

Recognition of ASF1 Using Hydrocarbon Constrained Peptides

Inhibition of the histone H3-ASF1 (anti-silencing function 1) protein-protein interaction (PPI) represents a potential approach for treatment of numerous cancers. As an α-helix mediated PPI, constraint of the key histone H3 helix (residues 118-135) represents a strategy through which chemical probes might be elaborated to test this hypothesis. In this work variant H3118-135 peptides bearing pentenyl glycine residues at i and i + 4 positions were constrained by olefin metathesis. Biophysical analyses revealed that promotion of a bioactive helical conformation depends on the position at which the constraint is introduced, but that potency of binding towards ASF1 is unaffected by the constraint and instead that enthalpy-entropy compensation occurs

Cover Feature: Recognition of ASF1 by Using Hydrocarbon‐Constrained Peptides (ChemBioChem 7/2019)

The cover feature picture shows how inhibition of the histone H3‐ASF1 (anti‐silencing function 1) protein–protein interaction (PPI) represents a potential approach for the treatment of numerous cancers. To pursue this goal, a hydrocarbon constraint was used to pre‐organize the histone H3 peptide in α‐helical conformation; despite conferring protection against proteolysis, this constrained peptide unexpectedly exhibited enthalpy–entropy compensation in comparison to the natural sequence, in its binding of ASF1. More information can be found in the communication by F. Ochsenbein, A. J. Wilson et al. on page 891 in Issue 7, 2019 (DOI: 10.1002/cbic.201800633)