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The Zika virus (ZIKV) disease caused a public health emergency of international concern that started in February 2016. The overall number of ZIKV-related cases increased until November 2016, after which it declined sharply. While the evaluation of the potential risk and impact of future arbovirus epidemics remains challenging, intensified surveillance efforts along with a scale-up of ZIKV whole-genome sequencing provide an opportunity to understand the patterns of genetic diversity, evolution, and spread of ZIKV. However, a classification system that reflects the true extent of ZIKV genetic variation is lacking. Our objective was to characterize ZIKV genetic diversity and phylodynamics, identify genomic footprints of differentiation patterns, and propose a dynamic classification system that reflects its divergence levels. We analysed a curated dataset of 762 publicly available sequences spanning the full-length coding region of ZIKV from across its geographical span and collected between 1947 and 2021. The definition of genetic groups was based on comprehensive evolutionary dynamics analyses, which included recombination and phylogenetic analyses, within- and between-group pairwise genetic distances comparison, detection of selective pressure, and clustering analyses. Evidence for potential recombination events was detected in a few sequences. However, we argue that these events are likely due to sequencing errors as proposed in previous studies. There was evidence of strong purifying selection, widespread across the genome, as also detected for other arboviruses. A total of 50 sites showed evidence of positive selection, and for a few of these sites, there was amino acid (AA) differentiation between genetic clusters. Two main genetic clusters were defined, ZA and ZB, which correspond to the already characterized ‘African’ and ‘Asian’ genotypes, respectively. Within ZB, two subgroups, ZB.1 and ZB.2, represent the Asiatic and the American (and Oceania) lineages, respectively. ZB.1 is further subdivided into ZB.1.0 (a basal Malaysia sequence sampled in the 1960s and a recent Indian sequence), ZB.1.1 (South-Eastern Asia, Southern Asia, and Micronesia sequences), and ZB.1.2 (very similar sequences from the outbreak in Singapore). ZB.2 is subdivided into ZB.2.0 (basal American sequences and the sequences from French Polynesia, the putative origin of South America introduction), ZB.2.1 (Central America), and ZB.2.2 (Caribbean and North America). This classification system does not use geographical references and is flexible to accommodate potential future lineages. It will be a helpful tool for studies that involve analyses of ZIKV genomic variation and its association with pathogenicity and serve as a starting point for the public health surveillance and response to on-going and future epidemics and to outbreaks that lead to the emergence of new variants. publishersversion published

The ongoing coronavirus (CoV) disease 2019 (COVID-19) pandemic caused by infection with severe acute respiratory syndrome CoV 2 (SARS-CoV-2) is associated with substantial morbidity and mortality. Understanding the immunological and patho-logical processes of coronavirus diseases is crucial for the rational design of effective vaccines and therapies for COVID-19. Previous studies showed that 2'-O-methylation of the viral RNA cap structure is required to prevent the recognition of viral RNAs by intra-cellular innate sensors. Here, we demonstrate that the guanine N7-methylation of the 5' cap mediated by coronavirus nonstructural protein 14 (nsp14) contributes to viral evasion of the type I interferon (IFN-I)-mediated immune response and pathogenesis in mice. A Y414A substitution in nsp14 of the coronavirus mouse hepatitis virus (MHV) significantly decreased N7-methyltransferase activity and reduced guanine N7-methyla-tion of the 5' cap in vitro. Infection of myeloid cells with recombinant MHV harboring the nsp14-Y414A mutation (rMHV(nsp14-Y414A)) resulted in upregulated expression of IFN-I and ISG15 mainly via MDA5 signaling and in reduced viral replication compared to that of wild-type rMHV. rMHV(nsp14-Y414A) replicated to lower titers in livers and brains and exhibited an attenuated phenotype in mice. This attenuated phenotype was IFN-I de-pendent because the virulence of the rMHV(nsp14-Y414A) mutant was restored in Ifnar(-/-) mice. We further found that the comparable mutation (Y420A) in SARS-CoV-2 nsp14 (rSARS-CoV-2(nsp14-Y420A)) also significantly decreased N7-methyltransferase activity in vitro, and the mutant virus was attenuated in K18-human ACE2 transgenic mice. Moreover, infection with rSARS-CoV-2(nsp14-Y420A) conferred complete protection against subsequent and otherwise lethal SARS-CoV-2 infection in mice, indicating the vaccine potential of this mutant.IMPORTANCE Coronaviruses (CoVs), including SARS-CoV-2, the cause of COVID-19, use several strategies to evade the host innate immune responses. While the cap struc-ture of RNA, including CoV RNA, is important for translation, previous studies indi-cate that the cap also contributes to viral evasion from the host immune response. In this study, we demonstrate that the N7-methylated cap structure of CoV RNA is pivotal for virus immunoevasion. Using recombinant MHV and SARS-CoV-2 encoding an inactive N7-methyltransferase, we demonstrate that these mutant viruses are highly attenuated in vivo and that attenuation is apparent at very early times after infection. Virulence is restored in mice lacking interferon signaling. Further, we show that infection with virus defective in N7-methylation protects mice from lethal SARSCoV-2, suggesting that the N7-methylase might be a useful target in drug and vaccine development.

The genome sequence is the only characteristic readily obtainable for all known viruses, underlying the growing role of comparative genomics in organizing knowledge about viruses in a systematic evolution-aware way, known as virus taxonomy. Overseen by the International Committee on Taxonomy of Viruses (ICTV), development of virus taxonomy involves taxa demarcation at 15 ranks of a hierarchical classification, often in host-specific manner. Outside the ICTV remit, researchers assess fitting numerous unclassified viruses into the established taxa. They employ different metrics of virus clustering, basing on conserved domain(s), separation of viruses in rooted phylogenetic trees and pair-wise distance space. Computational approaches differ further in respect to methodology, number of ranks considered, sensitivity to uneven virus sampling, and visualization of results. Advancing and using computational tools will be critical for improving taxa demarcation across the virosphere and resolving rank origins in research that may also inform experimental virology. Copyrigh

Two pandemics of respiratory distress diseases associated with zoonotic introductions of the species Severe acute respiratory syndrome-related coronavirus in the human population during 21st century raised unprecedented interest in coronavirus research and assigned it unseen urgency. The two viruses responsible for the outbreaks, SARS-CoV and SARS-CoV-2, respectively, are in the spotlight, and SARSCoV-2 is the focus of the current fast-paced research. Its foundation was laid down by studies of many coronaand related viruses that collectively form the vast order Nidovirales. Comparative genomics of nidoviruses played a key role in this advancement over more than 30 years. It facilitated the transfer of knowledge from characterized to newly identified viruses, including SARS-CoV and SARS-CoV-2, as well as contributed to the dissection of the nidovirus proteome and identification of patterns of variations between different taxonomic groups, from species to families. This review revisits selected cases of protein conservation and variation that define nidoviruses, illustrates the remarkable plasticity of the proteome during nidovirus adaptation, and asks questions at the interface of the proteome and processes that are vital for nidovirus reproduction and could inform the ongoing research of SARS-CoV-2. (c) 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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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