Strategies of rational and structure-driven vaccine design for Arenaviruses.

The COVID-19 outbreak has highlighted the importance of pandemic preparedness for the prevention of future health crises. One virus family with high pandemic potential are Arenaviruses, which have been detected almost worldwide, particularly in Africa and the Americas. These viruses are highly understudied and many questions regarding their structure, replication and tropism remain unanswered, making the design of an efficacious and molecularly-defined vaccine challenging. We propose that structure-driven computational vaccine design will contribute to overcome these challenges. Computational methods for stabilization of viral glycoproteins or epitope focusing have made progress during the last decades and particularly during the COVID-19 pandemic, and have proven useful for rational vaccine design and the establishment of novel diagnostic tools. In this review, we summarize gaps in our understanding of Arenavirus molecular biology, highlight challenges in vaccine design and discuss how structure-driven and computationally informed strategies will aid in overcoming these obstacles.

Backbone chemical shift and secondary structure assignments for mouse siderocalin.

The lipocalin protein family is a structurally conserved group of proteins with a variety of biological functions defined by their ability to bind small molecule ligands and interact with partner proteins. One member of this family is siderocalin, a protein found in mammals. Its role is discussed in inflammatory processes, iron trafficking, protection against bacterial infections and oxidative stress, cell migration, induction of apoptosis, and cancer. Though it seems to be involved in numerous essential pathways, the exact mechanisms are often not fully understood. The NMR backbone assignments for the human siderocalin and its rat ortholog have been published before. In this work we describe the backbone NMR assignments of siderocalin for another important model organism, the mouse - data that might become important for structure-based drug discovery. Secondary structure elements were predicted based on the assigned backbone chemical shifts using TALOS-N and CSI 3.0, revealing a high content of beta strands and one prominent alpha helical region. Our findings correlate well with the known crystal structure and the overall conserved fold of the lipocalin family.

Truck Platooning Under Real Traffic Conditions: First Insights on Behavioral Adaptations and Gap Preference of Professional Drivers.

OBJECTIVE: The aim of the study was to investigate (1) how different gap sizes are perceived by professional truck drivers under real traffic conditions and (2) whether semi-automated platoon driving leads to changes in driving behavior of subsequent manual driving. BACKGROUND: Platoon driving is a current branch in the development of automated driving in which two or more vehicles build a convoy. The lead vehicle is controlled manually while following vehicles are electronically coupled to it and drive semi-automated with small gaps in order to achieve a better traffic flow and potential fuel savings. METHOD: In a real road experiment, 10 trained professional truck drivers completed a total of 33 test drives with a two-truck platoon on the German highway A9 with a gap size of either 15 or 21 m, in the leading and the following vehicle. RESULTS: (1) The drivers experienced both gap sizes as comfortable and preferred the smaller gap size of 15 m. (2) Both gap sizes led to significantly higher standard deviation of lane position in post- compared to pre-platoon driving. No significant difference in distance keepings in post- compared to pre-platoon driving occurred. Qualitative data give hints on difficulties, when switching back to regular truck driving. CONCLUSION: The results implicate that small gap sizes are perceived as comfortable by drivers and that platoon driving has an influence on subsequent manual driving. APPLICATION: Countermeasures to behavioral adaptations should be considered in order to ensure a safe conduction of platoon driving.