Chapter 2: What Is Life?

The question "What is life?" has existed since the beginning of recorded history. However, the scientific and philosophical contexts of this question have changed and been refined as advancements in technology have revealed both fine details and broad connections in the network of life on Earth. Understanding the framework of the question "What is life?" is central to formulating other questions such as "Where else could life be?" and "How do we search for life elsewhere?" While many of these questions are addressed throughout the Astrobiology Primer 3.0, this chapter gives historical context for defining life, highlights conceptual characteristics shared by all life on Earth as well as key features used to describe it, discusses why it matters for astrobiology, and explores both challenges and opportunities for finding an informative operational definition.

Chapter 1: The Astrobiology Primer 3.0.

The Astrobiology Primer 3.0 (ABP3.0) is a concise introduction to the field of astrobiology for students and others who are new to the field of astrobiology. It provides an entry into the broader materials in this supplementary issue of Astrobiology and an overview of the investigations and driving hypotheses that make up this interdisciplinary field. The content of this chapter was adapted from the other 10 articles in this supplementary issue and thus represents the contribution of all the authors who worked on these introductory articles. The content of this chapter is not exhaustive and represents the topics that the authors found to be the most important and compelling in a dynamic and changing field.

Structural Analysis of Monomeric RNA-Dependent Polymerases Revisited.

In the past few years, our understanding of the RNA virosphere has changed dramatically due to the growth and spurt of metagenomics, exponentially increasing the number of RNA viral sequences, and providing a better understanding of their range of potential hosts. As of today, the only conserved protein among RNA viruses appears to be the monomeric RNA-dependent RNA polymerase. This enzyme belongs to the right-hand DNA-and RNA polymerases, which also includes reverse transcriptases and eukaryotic replicative DNA polymerases. The ubiquity of this protein in RNA viruses makes it a unique evolutionary marker and an appealing broad-spectrum antiviral target. In this work pairwise structural comparisons of viral RdRps and RTs were performed, including tertiary structures that have been obtained in the last few years. The resulting phylogenetic tree shows that the RdRps from (+)ss- and dsRNA viruses might have been recruited several times throughout the evolution of mobile genetic elements. RTs also display multiple evolutionary routes. We have identified a structural core comprising the entire palm, a large moiety of the fingers and the N-terminal helices of the thumb domain, comprising over 300 conserved residues, including two regions that we have named the "knuckles" and the "hypothenar eminence". The conservation of an helix bundle in the region preceding the polymerase domain confirms that (-)ss and dsRNA Reoviruses' polymerases share a recent ancestor. Finally, the inclusion of DNA polymerases into our structural analyses suggests that monomeric RNA-dependent polymerases might have diverged from B-family polymerases.

Two short low complexity regions (LCRs) are hallmark sequences of the Delta SARS-CoV-2 variant spike protein.

Low complexity regions (LCRs) are protein sequences formed by a set of compositionally biased residues. LCRs are extremely abundant in cellular proteins and have also been reported in viruses, where they may partake in evasion of the host immune system. Analyses of 28,231 SARS-CoV-2 whole proteomes and of 261,051 spike protein sequences revealed the presence of four extremely conserved LCRs in the spike protein of several SARS-CoV-2 variants. With the exception of Iota, where it is absent, the Spike LCR-1 is present in the signal peptide of 80.57% of the Delta variant sequences, and in other variants of concern and interest. The Spike LCR-2 is highly prevalent (79.87%) in Iota. Two distinctive LCRs are present in the Delta spike protein. The Delta Spike LCR-3 is present in 99.19% of the analyzed sequences, and the Delta Spike LCR-4 in 98.3% of the same set of proteins. These two LCRs are located in the furin cleavage site and HR1 domain, respectively, and may be considered hallmark traits of the Delta variant. The presence of the medically-important point mutations P681R and D950N in these LCRs, combined with the ubiquity of these regions in the highly contagious Delta variant opens the possibility that they may play a role in its rapid spread.

Sofosbuvir as a potential alternative to treat the SARS-CoV-2 epidemic.

As of today, there is no antiviral for the treatment of the SARS-CoV-2 infection, and the development of a vaccine might take several months or even years. The structural superposition of the hepatitis C virus polymerase bound to sofosbuvir, a nucleoside analog antiviral approved for hepatitis C virus infections, with the SARS-CoV polymerase shows that the residues that bind to the drug are present in the latter. Moreover, a multiple alignment of several SARS-CoV-2, SARS and MERS-related coronaviruses polymerases shows that these residues are conserved in all these viruses, opening the possibility to use sofosbuvir against these highly infectious pathogens.

A yellow flag on the horizon: The looming threat of yellow fever to North America.

OBJECTIVES: Yellow fever virus historically was a frequent threat to American and European coasts. Medical milestones such as the discovery of mosquitoes as vectors and subsequently an effective vaccine significantly reduced its incidence, in spite of which, thousands of cases of this deathly disease still occur regularly in Sub-Saharan Africa and the Amazonian basin in South America, which are usually not reported. An urban outbreak in Angola, consecutive years of increasing incidence near major Brazilian cities, and imported cases in China, South America and Europe, have brought this virus back to the global spotlight. The aim of this article is to underline that the preventive YFV measures, such as vaccination, need to be carefully revised in order to minimize the risks of new YFV outbreaks, especially in urban or immunologically vulnerable places. Furthermore, this article highlights the diverse factors that have favored the spread of other Aedes spp.-associated arboviral diseases like Dengue, Chikungunya and Zika, to northern latitudes causing epidemics in the United States and Europe, emphasizing the possibility that YFV might follow the path of these viruses unless enhanced surveillance and efficient control systems are urgently initiated.