Bats of different species play a major role in the emergence and transmission of highly pathogenic viruses including Ebola virus, SARS-like coronavirus and the henipaviruses. These viruses require proteolytic activation of surface envelope glycoproteins needed for entry, and cellular cathepsins have been shown to be involved in proteolysis of glycoproteins from these distinct virus families. Very little is currently known about the available proteases in bats. To determine whether the utilization of cathepsins by bat-borne viruses is related to the nature of proteases in their natural hosts, we examined proteolytic processing of several viral fusion proteins in cells derived from two fruit bat species, Pteropus alecto and Rousettus aegyptiacus. Our work shows that fruit bat cells have homologs of cathepsin and furin proteases capable of cleaving and activating both the cathepsin-dependent Hendra virus F and the furin-dependent parainfluenza virus 5 F proteins. Sequence analysis comparing Pteropus alecto furin and cathepsin L to proteases from other mammalian species showed a high degree of conservation; however significant amino acid variation occurs at the C-terminus of Pteropus alecto furin. Further analysis of furin-like proteases from fruit bats revealed that these proteases are catalytically active and resemble other mammalian furins in their response to a potent furin inhibitor. However, kinetic analysis suggests that differences may exist in the cellular localization of furin between different species. Collectively, these results indicate that the unusual role of cathepsin proteases in the life cycle of bat-borne viruses is not due to the lack of active furin-like proteases in these natural reservoir species; however, differences may exist between furin proteases present in fruit bats compared to furins in other mammalian species, and these differences may impact protease usage for viral glycoprotein processing.

Polyphenolic compounds including a number of natural products such as resveratrol, curcumin, catechin derivatives, and nordihydroguaiaretic acid have effects on the assembly of Aβ fibrils and oligomers as well as on fibril morphology. Based on a lead structure obtained from a screen of a small molecule diversity library, simple benzoic acid derivatives distinguished by the number and position of hydroxyls on the aromatic ring displayed different abilities to dissociate pre-formed biotinyl-Aβ(1–42) oligomers. The 2, 3-, 2, 5-, and 3, 4- dihydroxybenzoic acid (DHBA) isomers were active oligomer dissociators. The remaining DHBA isomers and the monohydroxy and unsubstituted benzoic acids were inactive and did not compete with the active compounds to block oligomer dissociation. None of the compounds blocked oligomer assembly, indicating that they do not interact with monomeric Aβ to shift the oligomer-monomer equilibrium. Dissociating activity was not associated with quinone redox cycling capacity of the compounds. Gallic acid (3, 4, 5-trihydroxybenzoic acid) stabilized biotinyl-Aβ(1–42) oligomers against intrinsic dissociation and blocked the effects of the active dissociators, independent of the concentration of dissociator. A model for the mechanism of action of the DHBA dissociators proposes that these compounds destabilize oligomer structure promoting progressive monomer dissociation rather than fissioning oligomers into smaller, but still macromolecular species. Gallic acid blocks dissociation by stabilizing oligomers against this process.

In the selection of candidates for post-combustion CO 2 absorption, solvent degradation has become a general concern due to the significant impact on operational cost and the intention to use thermal compression from high temperature stripping to minimize the overall process energy. In this research, structural analogs of amino acid salts, alkanolamines and diamines were thermally degraded in order to explore their thermal stability from a structural standpoint. Functional groups, amine orders and steric effect were investigated for their impact on amine thermal degradation. Primary amines with chain structures showed a thermal stability trend as diamine > alkanolamine > amino acid salt. For alknolamine and diamine structural isomers, the primary amines are more stable than the secondary amines. Steric hindrance around the amine group was shown to play a positive role in protecting amines against thermal degradation.

No abstract