ABSTRACT
SARS-CoV-2 has a zoonotic origin and was transmitted to humans via an undetermined intermediate host, leading to infections in humans and other mammals. To enter host cells, the viral spike protein (S-protein) binds to its receptor, ACE2, and is then processed by TMPRSS2. Whilst receptor binding contributes to the viral host range, S-protein:ACE2 complexes from other animals have not been investigated widely. To predict infection risks, we modelled S-protein:ACE2 complexes from 215 vertebrate species, calculated changes in the energy of the complex caused by mutations in each species, relative to human ACE2, and correlated these changes with COVID-19 infection data. We also analysed structural interactions to better understand the key residues contributing to affinity. We predict that mutations are more detrimental in ACE2 than TMPRSS2. Finally, we demonstrate phylogenetically that human SARS-CoV-2 strains have been isolated in animals. Our results suggest that SARS-CoV-2 can infect a broad range of mammals, but few fish, birds or reptiles. Susceptible animals could serve as reservoirs of the virus, necessitating careful ongoing animal management and surveillance.
Subject(s)
Peptidyl-Dipeptidase A/chemistry , Phylogeny , Spike Glycoprotein, Coronavirus/chemistry , Angiotensin-Converting Enzyme 2 , Animals , Betacoronavirus/classification , Betacoronavirus/genetics , Humans , Mammals , Molecular Docking Simulation , Mutation , Peptidyl-Dipeptidase A/classification , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Protein Binding , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolismABSTRACT
The blood supply of the growth plate has been described in the late 50s and early 60s, and there was controversial discussion about the existence of transphyseal vessels. The vascular supply of growth plate and epiphysis of the proximal tibia was reinvestigated using a modern technique, the Mercox-perfusion method, in six sheep aged 6-24 weeks. A comparison was made among pure perfusion specimens, the corrosion casts, and histological sections. The metaphyseal, epiphyseal, and perichondral blood supply systems were confirmed. However, there was evidence of regular transphyseal anastomoses between the metaphyseal and epiphyseal system. Based on the histological arrangement of the blood vessels, the arterial blood flow would appear to be from the metaphysis to the epiphysis. The existence of transphyseal arterial vessels originating metaphyseally and seen both in cast preparations and histological sections was added to the present description of the blood supply of the growth plate. Age-related differences in the vascularization of the growth plate were not found in this study.
