The SARS-CoV-2 Spike protein has a broad tropism for mammalian ACE2 proteins

SARS Coronavirus 2 (SARS-CoV-2) emerged in late 2019, leading to the Coronavirus Disease 2019 (COVID-19) pandemic that continues to cause significant global mortality in human populations. Given its sequence similarity to SARS-CoV, as well as related coronaviruses circulating in bats, SARS-CoV-2 is thought to have originated in Chiroptera species in China. However, whether the virus spread directly to humans or through an intermediate host is currently unclear, as is the potential for this virus to infect companion animals, livestock, and wildlife that could act as viral reservoirs. Using a combination of surrogate entry assays and live virus, we demonstrate that, in addition to human angiotensin-converting enzyme 2 (ACE2), the Spike glycoprotein of SARS-CoV-2 has a broad host tropism for mammalian ACE2 receptors, despite divergence in the amino acids at the Spike receptor binding site on these proteins. Of the 22 different hosts we investigated, ACE2 proteins from dog, cat, and cattle were the most permissive to SARS-CoV-2, while bat and bird ACE2 proteins were the least efficiently used receptors. The absence of a significant tropism for any of the 3 genetically distinct bat ACE2 proteins we examined indicates that SARS-CoV-2 receptor usage likely shifted during zoonotic transmission from bats into people, possibly in an intermediate reservoir. Comparison of SARS-CoV-2 receptor usage to the related coronaviruses SARS-CoV and RaTG13 identified distinct tropisms, with the 2 human viruses being more closely aligned. Finally, using bioinformatics, structural data, and targeted mutagenesis, we identified amino acid residues within the Spike–ACE2 interface, which may have played a pivotal role in the emergence of SARS-CoV-2 in humans. The apparently broad tropism of SARS-CoV-2 at the point of viral entry confirms the potential risk of infection to a wide range of companion animals, livestock, and wildlife.

A study using a combination of surrogate entry assays and live virus suggests that SARS-CoV-2 may have a broad host-range, revealing that the virus''s spike protein can use a broad range of host ACE2 receptors to enter cells and that the sequence of this protein might have changed during the zoonotic jump into humans.     

Comparative studies of social behavior in Callicebus and Saimiri: Behavioral and physiological responses of established pairs to unfamiliar pairs

The influences of cage size and novelty on the behavior of Galago senegalensis braccatus were examined in two captive groups (five adults and one immature per group) having similarly furnished but unequally sized cages. One group experienced expansion, and the other experienced contraction of space. Each group experienced the novelty of a new cage and return to its old cage. Exploration, nonsocial activity, and social sniffing behaviors were most frequent in both groups during the novelty phase independent of cage size. These behaviors remained elevated after return to the original cage. This pattern indicated that novelty, not space, was responsible for these behavioral changes. The increase in social sniffing indicated that group members may use olfactory cues to recognize each other, expecially when the setting is novel. In both groups, frequencies of displacements and chases were highest in the smaller space. Group differences in behavior prior to cage change also influenced a group's response to change.     

Quantitation of o-, m- and p-cresol and deuterated analogs in human urine by gas chromatography with electron capture detection

A gas chromatographic method for the analysis of cresol metabolites of toluene and [²H₈]toluene in urine was developed. Cresol glucuronides and sulfates in urine were hydrolyzed with β-glucuronidase and arylsulfatase. Following extraction with tert.-butyl methyl ether and solvent exchange into benzene, the cresols were derivatized with heptafluorobutyric anhydride to form the heptafluorobutyrate esters. The derivatives were analyzed by gas chromatography with electron capture detection. Chromatographic resolution was achieved between all cresol isomers and their ²H₇ analogs. Calibration ranged from 0.001 to 500 μg/ml. Recoveries were 55–97% and showed no trend with respect to analyte concentration. Within-day precision of analyses of benchmark urine samples had a coefficient of variation of less than 4%. The assay sensitivity was limited by chromatographic background but was sufficient for quantification of the unlabeled cresols in urine from men with only environmental exposure to toluene. Average levels in urine samples from 45 men were 0.023, 0.054 and 37 μg/ml for o-, m- and p-cresol, respectively.     

Site preparation impacts on soil biotic and abiotic properties,weed control,and native grass establishment

In severely degraded systems active restoration is required to overcome legacies of past land use and to create conditions that promote the establishment of target plant communities. While our understanding of the importance of soil microbial communities in ecological restoration is growing, few studies have looked at the impacts different site preparation techniques have on these communities. We trialed four methods of site preparation: fire, top‐soil removal (TSR; removal of top 50 mm of soil), slashing (vegetation cut to 30 mm, biomass removed), and carbon (C; as sugar and saw‐dust) addition, and quantified resulting soil bacterial communities using DNA metabarcoding. We compared the effectiveness of these techniques to reduce weed biomass, improve native grass establishment, and induce changes in soil nutrient availability. TSR was the most effective technique, leading to a reduction in both available nutrients and competition from weeds. In comparison, the remaining methods had little or no effect on weed biomass, native grass establishment, or soil nutrient availability. Both TSR and C addition resulted in changes in the soil bacterial community. These changes have the potential to alter plant community assembly in many ways, such as via nutrient acquisition, pathogenic effects, nutrient cycling, and decomposition. We recommend TSR for ecological restoration of old‐fields and suggest it is a much more effective technique than burning, slashing, or C addition. Restoration practitioners should consider how their management techniques may influence the soil biota and, in turn, affect restoration outcomes.     

The synthesis and biological evaluation of non-peptidic matrix metalloproteinase inhibitors.

Novel sulfonamide matrix metalloproteinase inhibitors of general formula (9) were synthesised by a route involving a stereoselective conjugate addition reaction. Enzyme selectivity was found to be dependant on the nature of the sulfonamide substituents. Compounds (9f, 9q) are potent selective collagenase inhibitors with good oral bioavailability.