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Nidoviruses form a phylogenetically compact but diverse group of enveloped positive-stranded RNA viruses with the largest RNA genome known. They infect a broad range of hosts, including humans, other mammals, birds, fish, and shrimp. Nidovirus infection starts by binding to a receptor on the cell surface, and fusion of the viral and cellular membranes mediated by one of the major surface glycoproteins. Following genome uncoating, the translation of the two overlapping replicase open reading frames (ORFs) yields two large polyprotein precursors that undergo autoproteolysis to produce the mature nonstructural proteins that eventually assemble into a membrane-bound, replication–transcription complex. The complex, which also contains several cellular proteins, mediates negative-strand RNA synthesis, amplification of the genome RNA, and production of a nested set of subgenomic messenger RNAs (sg mRNAs). Whereas nidovirus genome replication proceeds through the synthesis of a full-length negative-strand RNA, transcription involves the synthesis of subgenome-length, negative-strand templates for mRNA synthesis. In arteriviruses and coronaviruses, and probably bafiniviruses, transcription involves a mechanism of discontinuous negative-strand synthesis (template switch) to equip each subgenomic RNA with a 5′ common leader sequence identical to the genomic 5′ end. Except for the largest torovirus sg RNA, torovirus and ronivirus sgRNAs do not share such a common leader sequence and discontinuous RNA synthesis does not appear to be involved in this case. New nidovirus particles are assembled in the cytoplasm. There is increasing evidence that nidovirus infections modify a variety of host cell functions and structures, and induce a variety of immune and stress responses.

O-Acetylation is a common modification of sialic acids that can occur at carbons 4-, 7-, 8-, and/or 9. Acetylated sialosides are employed as receptors by several betacoronaviruses and toroviruses, and by influenza C and D viruses. The molecular basis by which these viruses recognize specific O-acetylated sialosides is poorly understood, and it is unknown how viruses have evolved to recognize specific O-acetylated sialosides expressed by their host. Here, we describe a chemoenzymatic approach that can readily provide sialoglycan analogues in which acetyl esters at C4 and/or C7 are replaced by stabilizing acetamide moieties. The analogues and their natural counterparts were used to examine the ligand requirements of the lectin domain of coronaviral hemagglutinin-esterases (HEs). It revealed that HEs from viruses targeting different host species exhibit different requirements for O-acetylation. It also showed that ester-to-amide perturbation results in decreased or loss of binding. STD NMR and molecular modeling of the complexes of the HE of BCoV with the acetamido analogues and natural counterparts revealed that binding is governed by the complementarity between the acetyl moieties of the sialosides and the hydrophobic patches of the lectin. The precise spatial arrangement of these elements is important, and an ester-to-amide perturbation results in substantial loss of binding. Molecular Dynamics simulations with HEs from coronaviruses infecting other species indicate that these viruses have adapted their HE specificity by the incorporation of hydrophobic or hydrophilic elements to modulate acetyl ester recognition.

Eukaryotic cells, when exposed to environmental or internal stress, activate the integrated stress response (ISR) to restore homeostasis and promote cell survival. Specific stress stimuli prompt dedicated stress kinases to phosphorylate eukaryotic initiation factor 2 (eIF2). Phosphorylated eIF2 (p-eIF2) in turn sequesters the eIF2-specific guanine exchange factor eIF2B to block eIF2 recycling, thereby halting translation initiation and reducing global protein synthesis. To circumvent stress-induced translational shutdown, viruses encode ISR antagonists. Those identified so far prevent or reverse eIF2 phosphorylation. We now describe two viral proteins-one from a coronavirus and the other from a picornavirus-that have independently acquired the ability to counteract the ISR at its very core by acting as a competitive inhibitor of p-eIF2-eIF2B interaction. This allows continued formation of the eIF2-GTP-Met-tRNAi ternary complex and unabated global translation at high p-eIF2 levels that would otherwise cause translational arrest. We conclude that eIF2 and p-eIF2 differ in their interaction with eIF2B to such effect that p-eIF2-eIF2B association can be selectively inhibited.

Coronaviridae Study Group of the International Committee on Taxonomy of Viruses* The present outbreak of a coronavirus-associated acute respiratory disease called coronavirus disease 19 (COVID-19) is the third documented spillover of an animal coronavirus to humans in only two decades that has resulted in a major epidemic. The Coronaviridae Study Group (CSG) of the International Committee on Taxonomy of Viruses, which is responsible for developing the classification of viruses and taxon nomenclature of the family Coronaviridae, has assessed the placement of the human pathogen, tentatively named 2019-nCoV, within the Coronaviridae. Based on phylogeny, taxonomy and established practice, the CSG recognizes this virus as forming a sister clade to the prototype human and bat severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus, and designates it as SARS-CoV-2. In order to facilitate communication, the CSG proposes to use the following naming convention for individual isolates: SARS- CoV-2/host/location/isolate/date. While the full spectrum of clinical manifestations associated with SARS-CoV-2 infections in humans remains to be determined, the independent zoonotic transmission of SARS-CoV and SARS-CoV-2 highlights the need for studying viruses at the species level to complement research focused on individual pathogenic viruses of immediate significance. This will improve our understanding of virus–host interactions in an ever-changing environment and enhance our preparedness for future outbreaks. pon U a viral outbreak, it is important to rapidly establish whether the outbreak is caused by a new or a previously known virus (Box 1), as this helps decide which approaches and actions are most appropriate to detect the causative agent, con- trol its transmission and limit potential consequences of the epi- demic. The assessment of virus novelty also has implications for virus naming and, on a different timescale, helps to define research priorities in virology and public health. For many human virus infections such as influenza virus 1 or norovirus 2 infections, well-established and internationally approved methods, standards and procedures are in place to identify and name the causative agents of these infections and report this infor- mation promptly to public health authorities and the general public. In outbreaks involving newly emerged viruses, the situation may be different, and appropriate procedures to deal with these viruses need to be established or refined with high priority. Here, we present an assessment of the genetic relatedness of the newly identified human coronavirus 3, provisionally named 2019- nCoV, to known coronaviruses, and detail the basis for (re)naming this virus severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), which will be used hereafter. Given the public interest in nam- ing newly emerging viruses and the diseases caused by these viruses in humans, we will give a brief introduction to virus discovery and classification — specifically the virus species concept — and the roles of different bodies, such as the World Health Organization (WHO) and the International Committee on Taxonomy of Viruses (ICTV), in this process. We hope this will help readers to better understand the scientific approach we have taken to arrive at this name, and we will also discuss implications of this analysis and naming decision. Classifying and naming viruses and virus species Defining the novelty of viruses is one of the topics that virus classification deals with. The classification of RNA viruses needs to consider their inherent genetic variability, which often results in two or more viruses with non-identical but similar genome sequences being regarded as variants of the same virus. This immediately poses the question of how much difference to an existing group is large enough to recognize the candidate virus as a member of a new, distinct group. This question is answered in best practice by evaluating the degree of relatedness of the candidate virus to previously identified viruses infecting the same host or established monophy- letic groups of viruses, often known as genotypes or clades, which may or may not include viruses of different hosts. This is formally addressed in the framework of the official classification of virus taxonomy and is overseen and coordinated by the ICTV 4. Viruses are clustered in taxa in a hierarchical scheme of ranks in which the spe- cies represents the lowest and most populous rank containing the least diverged groups (taxa) of viruses (Box 2). The ICTV maintains a Study Group for each virus family. The Study Groups are respon- sible for assigning viruses to virus species and taxa of higher ranks, such as subgenera, genera and subfamilies. In this context they play an important role in advancing the virus species concept and highlighting its significance 5. Virus nomenclature is a formal system of names used to label viruses and taxa. The fact that there are names for nearly all viruses within a species is due to the historical perception of viruses as causative agents of specific diseases in specific hosts, and to the way we usually catalogue and classify newly discovered viruses, which increasingly includes viruses that have not been linked to any known disease in their respective hosts (Box 1). The WHO, an agency of the United Nations, coordinates international public health activities aimed at combating, containing and mitigating the consequences of communicable diseases—including major virus epidemics—and is responsible for naming disease(s) caused by newly emerging human viruses. In doing so, the WHO often takes the traditional approach of linking names of specific diseases to viruses (Box 1) and *A list of authors and their affiliations appears at the end of the paper. assessing virus novelty by an apparent failure to detect the causative agent using established diagnostic assays. Apart from disease, geography and the organism from which a given virus was isolated also dominate the nomenclature, occasionally engraving connections that may be accidental (rather than typical) or even stigmatizing, which should be avoided. Establishing a universal nomenclature for viruses was one of the major tasks of the ICTV when it was founded more than 50 years ago 4. When the species rank was established in the taxonomy of viruses 6, ICTV’s responsibility for naming viruses was shifted to naming and establishing species. ICTV Study Groups may also be involved in virus naming on a case-by-case basis as an extension of their official remit, as well as using the special expertise of their members. As virus species names are often very similar to the name of the founding member of the respective species, they are frequently confused in the literature with names of individual viruses in this species. The species name is italicized, starts with a capital letter and should not be spelled in an abbreviated form 7; hence the species name Severe acute respiratory syndrome-related coronavirus. In contrast, this convention does not apply to virus names, hence severe acute respiratory syndrome coronavirus, or SARS-CoV, as it is widely known., Published as part of Gorbalenya, Alexander E., Baker, Susan C., Baric, Ralph S., de Groot, Raoul J., Drosten, Christian, Gulyaeva, Anastasia A., Haagmans, Bart L., Lauber, Chris, Leontovich, Andrey M., Neuman, Benjamin W., Penzar, Dmitry, Perlman, Stanley, Poon, Leo L. M., Samborskiy, Dmitry V., Sidorov, Igor A., Sola, Isabel & Ziebuhr, John, 2020, The species Severe acute respiratory syndromerelated coronavirus: classifying 2019 - nCoV and naming it SARS-CoV- 2, pp. 536-544 in Nature Microbiology 5 on pages 536-537, DOI: 10.1038/s41564-020-0695-z, http://zenodo.org/record/3725837, {"references":["1. Krammer, F. et al. Influenza. Nat. Rev. Dis. Primers 4, 3 (2018).","2. Zheng, D. P. et al. Norovirus classification and proposed strain nomenclature. Virology 346, 312 - 323 (2006).","3. Wu, A. et al. 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