Interspecies transmission of SARS CoV-2 with special emphasis on viral mutations and ACE-2 receptor homology roles.

COVID-19 outbreak was first reported in 2019, Wuhan, China. The spillover of the disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), to a wide range of pet, zoo, wild, and farm animals has emphasized potential zoonotic and reverse zoonotic viral transmission. Furthermore, it has evoked inquiries about susceptibility of different animal species to SARS-CoV-2 infection and role of these animals as viral reservoirs. Therefore, studying susceptible and non-susceptible hosts for SARS-CoV-2 infection could give a better understanding for the virus and will help in preventing further outbreaks. Here, we review structural aspects of SARS-CoV-2 spike protein, the effect of the different mutations observed in the spike protein, and the impact of ACE2 receptor variations in different animal hosts on inter-species transmission. Moreover, the SARS-CoV-2 spillover chain was reviewed. Combination of SARS-CoV-2 high mutation rate and homology of cellular ACE2 receptors enable the virus to transcend species barriers and facilitate its transmission between humans and animals.

Mutations of the SARS-CoV-2 Spike Glycoprotein Detected in Cats and Their Effect on Its Structure and Function.

The high frequency of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) mutations and homology of the Angiotensin-Converting Enzyme-2 (ACE2) cell receptors in various hosts help the virus transcend species barriers. In this study, we investigated the mutations of the SARS-CoV-2 spike glycoprotein detected in cats and their effect on its structure and function. Interestingly, some of these mutations are reported here in cats for the first time. Structural analysis showed seven residue substitutions in the spike glycoprotein. Four of the detected mutations are located on the spike surface, which are critical interaction points for neutralizing antibodies. Furthermore, three of the reported mutations could facilitate viral binding to the ACE2 host receptor, influence S1/S2 cleavage, destabilize the ß-hairpin structure of the S2 and enhance viral infectivity. Structural modeling and phylogenic analysis of the ACE2 receptor provided an indication of the binding capacity of the virus to the specific cell receptors of different species and hosts. The presented work highlights the effects of the residue substitutions on viral evasion, infectivity and possibility of SARS-CoV-2 spillover between humans and cats. In addition, the work paves the way for in-depth molecular investigation into the relationship between SARS-CoV-2 receptor binding and host susceptibility.

Statistical mechanical prediction of ligand perturbation to RNA secondary structure and application to riboswitches.

The realization that noncoding RNA is implicated in numerous cellular processes, makes it imperative to understand and predict RNA-folding. RNA secondary structure prediction is more tractable than tertiary structure or protein structure. Yet insights into RNA structure-function relationships are complicated by coupling between RNA-folding and ligand-binding. Here, perturbations to equilibrium secondary structure conformational distributions for two riboswitches are calculated in the presence of bound cognate ligands. This work incorporates a key factor coupling ligand binding to RNA conformation but not considered in most previous calculations: the differential affinity of the ligand for a range of RNA-folding intermediates. Significant shifts in the free energy landscape (FEL) due to the ligand occur for transcripts of lengths corresponding to the "decision window," following transcription of the so-called anti-terminator helix. The results suggest how ligand perturbation can stabilize the formation of an intermediate conformation, readily facilitating terminator hairpin formation in the full-length riboswitch.

Electron Tomography: A Three-Dimensional Analytic Tool for Hard and Soft Materials Research.

Three-dimensional (3D) structural analysis is essential to understand the relationship between the structure and function of an object. Many analytical techniques, such as X-ray diffraction, neutron spectroscopy, and electron microscopy imaging, are used to provide structural information. Transmission electron microscopy (TEM), one of the most popular analytic tools, has been widely used for structural analysis in both physical and biological sciences for many decades, in which 3D objects are projected into two-dimensional (2D) images. In many cases, 2D-projection images are insufficient to understand the relationship between the 3D structure and the function of nanoscale objects. Electron tomography (ET) is a technique that retrieves 3D structural information from a tilt series of 2D projections, and is gradually becoming a mature technology with sub-nanometer resolution. Distinct methods to overcome sample-based limitations have been separately developed in both physical and biological science, although they share some basic concepts of ET. This review discusses the common basis for 3D characterization, and specifies difficulties and solutions regarding both hard and soft materials research. It is hoped that novel solutions based on current state-of-the-art techniques for advanced applications in hybrid matter systems can be motivated.

Characterization of the host-guest complex of a curcumin analog with ß-cyclodextrin and ß-cyclodextrin-gemini surfactant and evaluation of its anticancer activity.

BACKGROUND: Curcumin analogs, including the novel compound NC 2067, are potent cytotoxic agents that suffer from poor solubility, and hence, low bioavailability. Cyclodextrin-based carriers can be used to encapsulate such agents. In order to understand the interaction between the two molecules, the physicochemical properties of the host-guest complexes of NC 2067 with ß-cyclodextrin (CD) or ß-cyclodextrin-gemini surfactant (CDgemini surfactant) were investigated for the first time. Moreover, possible supramolecular structures were examined in order to aid the development of new drug delivery systems. Furthermore, the in vitro anticancer activity of the complex of NC 2067 with CDgemini surfactant nanoparticles was demonstrated in the A375 melanoma cell line. METHODS: Physicochemical properties of the complexes formed of NC 2067 with CD or CDgemini surfactant were investigated by synchrotron-based powder X-ray diffraction, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. Synchrotron-based small- and wide-angle X-ray scattering and size measurements were employed to assess the supramolecular morphology of the complex formed by NC 2067 with CDgemini surfactant. Lastly, the in vitro cell toxicity of the formulations toward A375 melanoma cells at various drug-to-carrier mole ratios were measured by cell viability assay. RESULTS: Physical mixtures of NC 2067 and CD or CDgemini surfactant showed characteristics of the individual components, whereas the complex of NC 2067 and CD or CDgemini surfactant presented new structural features, supporting the formation of the host-guest complexes. Complexes of NC 2067 with CDgemini surfactants formed nanoparticles having sizes of 100-200 nm. NC 2067 retained its anticancer activity in the complex with CDgemini surfactant for different drug-to-carrier mole ratios, with an IC50 (half-maximal inhibitory concentration) value comparable to that for NC 2067 without the carrier. CONCLUSION: The formation of host-guest complexes of NC 2067 with CD or CDgemini surfactant has been confirmed and hence the CDgemini surfactant shows good potential to be used as a delivery system for anticancer agents.

Identification of novel conserved functional motifs across most Influenza A viral strains.

BACKGROUND: Influenza A virus poses a continuous threat to global public health. Design of novel universal drugs and vaccine requires a careful analysis of different strains of Influenza A viral genome from diverse hosts and subtypes. We performed a systematic in silico analysis of Influenza A viral segments of all available Influenza A viral strains and subtypes and grouped them based on host, subtype, and years isolated, and through multiple sequence alignments we extrapolated conserved regions, motifs, and accessible regions for functional mapping and annotation. RESULTS: Across all species and strains 87 highly conserved regions (conservation percentage > = 90%) and 19 functional motifs (conservation percentage = 100%) were found in PB2, PB1, PA, NP, M, and NS segments. The conservation percentage of these segments ranged between 94-98% in human strains (the most conserved), 85-93% in swine strains (the most variable), and 91-94% in avian strains. The most conserved segment was different in each host (PB1 for human strains, NS for avian strains, and M for swine strains). Target accessibility prediction yielded 324 accessible regions, with a single stranded probability > 0.5, of which 78 coincided with conserved regions. Some of the interesting annotations in these regions included sites for protein-protein interactions, the RNA binding groove, and the proton ion channel. CONCLUSIONS: The influenza virus has evolved to adapt to its host through variations in the GC content and conservation percentage of the conserved regions. Nineteen universal conserved functional motifs were discovered, of which some were accessible regions with interesting biological functions. These regions will serve as a foundation for universal drug targets as well as universal vaccine design.