Structural and Evolutionary Insights Into the Binding of Host Receptors by the Rabies Virus Glycoprotein.

Rabies represents a typical model for spillover of zoonotic viral diseases among multiple hosts. Understanding the success of rabies virus (RV) in switching hosts requires the analysis of viral evolution and host interactions. In this study, we have investigated the structural and sequence analysis of host receptors among different RV susceptible host species. Our extensive bioinformatic analysis revealed the absence of the integrin plexin domain in the integrin ß1 (ITGB1) receptor of the black fruit bats in the current annotation of the genome. Interestingly, the nicotinic acetyl choline receptor (nAChR) interaction site with the glycoprotein (G) of RV was conserved among different species. To study the interaction dynamics between RV-G protein and the RV receptors, we constructed and analyzed structures of RV receptors and G proteins using homology modeling. The molecular docking of protein-protein interaction between RV-G protein and different host receptors highlighted the variability of interacting residues between RV receptors of different species. These in silico structural analysis and interaction mapping of viral protein and host receptors establish the foundation to understand complex entry mechanisms of RV entry, which may facilitate the understanding of receptor mediated spillover events in RV infections and guide the development of novel vaccines to contain the infection.

Artificial Intelligence-Assisted Loop Mediated Isothermal Amplification (AI-LAMP) for Rapid Detection of SARS-CoV-2.

Until vaccines and effective therapeutics become available, the practical solution to transit safely out of the current coronavirus disease 19 (CoVID-19) lockdown may include the implementation of an effective testing, tracing and tracking system. However, this requires a reliable and clinically validated diagnostic platform for the sensitive and specific identification of SARS-CoV-2. Here, we report on the development of a de novo, high-resolution and comparative genomics guided reverse-transcribed loop-mediated isothermal amplification (LAMP) assay. To further enhance the assay performance and to remove any subjectivity associated with operator interpretation of results, we engineered a novel hand-held smart diagnostic device. The robust diagnostic device was further furnished with automated image acquisition and processing algorithms and the collated data was processed through artificial intelligence (AI) pipelines to further reduce the assay run time and the subjectivity of the colorimetric LAMP detection. This advanced AI algorithm-implemented LAMP (ai-LAMP) assay, targeting the RNA-dependent RNA polymerase gene, showed high analytical sensitivity and specificity for SARS-CoV-2. A total of ~200 coronavirus disease (CoVID-19)-suspected NHS patient samples were tested using the platform and it was shown to be reliable, highly specific and significantly more sensitive than the current gold standard qRT-PCR. Therefore, this system could provide an efficient and cost-effective platform to detect SARS-CoV-2 in resource-limited laboratories.

Enhanced protection against FMDV in cattle after prime- boost vaccination based on mucosal and inactivated FMD vaccine.

Improved immunization and control strategies and platforms are greatly needed for foot and mouth disease virus (FMDV) and mucosal vaccines propose an effective strategy for the control FMDV by blocking viral entry. In this study, several immunization strategies, using two FMDV vaccine formulations, including Montanide ISA 206 oil-based FMD inactivated vaccine and Montanide IMS 1313 VG N PR-based concentrated semi-purified FMD mucosal vaccine, were applied. Results of intranasal immunization with the prepared FMD mucosal vaccine, given once or twice, induced IgA levels in both nasal and salivary secretions besides a high response of lymphocyte proliferation with protection levels reaching 20% and 40%, respectively, in a challenge trial in cattle. Immunization with Montanide 206 inactivated FMD vaccine was capable of inducing 80% protection whereas prime-boost strategy based on the administration of mucosal vaccine followed by inactivated vaccine appeared to be the most potent strategy by achieving 100% protection against an FMDV challenge. Indeed, the study reports the efficacy of the prepared IMS 1313 FMD mucosal vaccine and the possible use of this vaccine in the context of different vaccination strategies to control FMDV.