Structural Characterization of SARS-CoV-2: Where We Are, and Where We Need to Be

Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China

(2020) Aiping Wu et al.   Cell Host & Microbe

Virus against virus: a potential treatment for 2019-nCov (SARS-CoV-2) and other RNA viruses

(2020) Tuan M. Nguyen et al.   CELL RESEARCH

Coronavirus Infections—More Than Just the Common Cold

(2020) Catharine I. Paules et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

The 2019‐new coronavirus epidemic: Evidence for virus evolution

(2020) Domenico Benvenuto et al.   JOURNAL OF MEDICAL VIROLOGY

COVID‐2019: The role of the nsp2 and nsp3 in its pathogenesis

(2020) Silvia Angeletti et al.   JOURNAL OF MEDICAL VIROLOGY

α-Ketoamides as Broad-Spectrum Inhibitors of Coronavirus and Enterovirus Replication: Structure-Based Design, Synthesis, and Activity Assessment

(2020) Linlin Zhang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

(2020) Chaolin Huang et al.   LANCET

A new coronavirus associated with human respiratory disease in China

(2020) Fan Wu et al.   NATURE

Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2

(2020) Renhong Yan et al.   SCIENCE

Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

(2020) Daniel Wrapp et al.   SCIENCE

RNA N6-Methyladenosine Modifications and the Immune Response

(2020) Ya-Nan Wang et al.   Journal of Immunology Research

Structural basis for RNA replication by the SARS-CoV-2 polymerase

(2020) Quan Wang et al.   CELL

Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2

(2020) Qihui Wang et al.   CELL

Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

(2020) Alexandra C. Walls et al.   CELL

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

(2020) Markus Hoffmann et al.   CELL

Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion

(2020) Shuai Xia et al.   CELL RESEARCH

SARS ‐CoV‐2 receptor ACE 2 and TMPRSS 2 are primarily expressed in bronchial transient secretory cells

(2020) Soeren Lukassen et al.   EMBO JOURNAL

Genotype and phenotype of COVID-19: Their roles in pathogenesis

(2020) Leila Mousavizadeh et al.   JOURNAL OF MICROBIOLOGY IMMUNOLOGY AND INFECTION

A Multibasic Cleavage Site in the Spike Protein of SARS-CoV-2 Is Essential for Infection of Human Lung Cells

(2020) Markus Hoffmann et al.   MOLECULAR CELL

A human neutralizing antibody targets the receptor binding site of SARS-CoV-2

(2020) Rui Shi et al.   NATURE

Human neutralizing antibodies elicited by SARS-CoV-2 infection

(2020) Bin Ju et al.   NATURE

Structure of replicating SARS-CoV-2 polymerase

(2020) Hauke S. Hillen et al.   NATURE

Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor

(2020) Jun Lan et al.   NATURE

A SARS-CoV-2 protein interaction map reveals targets for drug repurposing

(2020) David E. Gordon et al.   NATURE

Structural basis of receptor recognition by SARS-CoV-2

(2020) Jian Shang et al.   NATURE

Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors

(2020) Zhenming Jin et al.   NATURE

Structural basis for the inhibition of SARS-CoV-2 main protease by antineoplastic drug carmofur

(2020) Zhenming Jin et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Crystal structure of Nsp15 endoribonuclease NendoU from SARS‐CoV ‐2

(2020) Youngchang Kim et al.   PROTEIN SCIENCE

Controversies around the function of LARP1

(2020) Andrea J. Berman et al.   RNA Biology

Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease

(2020) Wenhao Dai et al.   SCIENCE

Structure of the RNA-dependent RNA polymerase from COVID-19 virus

(2020) Yan Gao et al.   SCIENCE

Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors

(2020) Linlin Zhang et al.   SCIENCE

Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir

(2020) Wanchao Yin et al.   SCIENCE

A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV

(2020) Meng Yuan et al.   SCIENCE

Novel Immunoglobulin Domain Proteins Provide Insights into Evolution and Pathogenesis of SARS-CoV-2-Related Viruses

(2020) Yongjun Tan et al.   mBio

Structural and biochemical characterization of nsp12-nsp7-nsp8 core polymerase complex from SARS-CoV-2

(2020) Qi Peng et al.   Cell Reports

Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites

(2020) Sisi Kang et al.   Acta Pharmaceutica Sinica B

A Structural View of SARS-CoV-2 RNA Replication Machinery: RNA Synthesis, Proofreading and Final Capping

(2020) Maria Romano et al.   Cells

Variant analysis of SARS-CoV-2 genomes

(2020) Takahiko Koyama et al.   BULLETIN OF THE WORLD HEALTH ORGANIZATION

The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity

(2020) Qianqian Li et al.   CELL

Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies

(2020) Christopher O. Barnes et al.   CELL

Structural Basis for Helicase-Polymerase Coupling in the SARS-CoV-2 Replication-Transcription Complex

(2020) James Chen et al.   CELL

Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients’ B Cells

(2020) Yunlong Cao et al.   CELL

Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike

(2020) Jiandong Huo et al.   Cell Host & Microbe

Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease

(2020) Chunlong Ma et al.   CELL RESEARCH

The ORF3a protein of SARS-CoV-2 induces apoptosis in cells

(2020) Yujie Ren et al.   Cellular & Molecular Immunology

Inhibition of SARS-CoV-2 by type I and type III interferons

(2020) Ulrike Felgenhauer et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Interferon-β-1a Inhibition of Severe Acute Respiratory Syndrome–Coronavirus 2 In Vitro When Administered After Virus Infection

(2020) Nicola Clementi et al.   JOURNAL OF INFECTIOUS DISEASES

Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike

(2020) Lihong Liu et al.   NATURE

Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report

(2020)   NEW ENGLAND JOURNAL OF MEDICINE

Architecture and self‐assembly of the SARS‐CoV ‐2 nucleocapsid protein

(2020) Qiaozhen Ye et al.   PROTEIN SCIENCE

A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2

(2020) Xiangyang Chi et al.   SCIENCE

Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients

(2020) Jérôme Hadjadj et al.   SCIENCE

Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2

(2020) Matthias Thoms et al.   SCIENCE

Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail

(2020) Johanna Hansen et al.   SCIENCE

Distinct conformational states of SARS-CoV-2 spike protein

(2020) Yongfei Cai et al.   SCIENCE

Activation and evasion of type I interferon responses by SARS-CoV-2

(2020) Xiaobo Lei et al.   Nature Communications

Structural plasticity of SARS-CoV-2 3CL Mpro active site cavity revealed by room temperature X-ray crystallography

(2020) Daniel W. Kneller et al.   Nature Communications

Interplay between SARS-CoV-2 and the type I interferon response

(2020) Margarida Sa Ribero et al.   PLoS Pathogens

Crystal Structure of the SARS-CoV-2 Non-structural Protein 9, Nsp9

(2020) Dene R. Littler et al.   iScience

TMPRSS2 and furin are both essential for proteolytic activation of SARS-CoV-2 in human airway cells

(2020) Dorothea Bestle et al.   Life Science Alliance

Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology

(2020) Luca Piccoli et al.   CELL

Structures and distributions of SARS-CoV-2 spike proteins on intact virions

(2020) Zunlong Ke et al.   NATURE

SARS-CoV-2 Nsp1 binds the ribosomal mRNA channel to inhibit translation

(2020) Katharina Schubert et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges

(2020) Beata Turoňová et al.   SCIENCE

Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein

(2020) Christine Toelzer et al.   SCIENCE

Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms

(2020) M. Alejandra Tortorici et al.   SCIENCE

The ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 inhibit type I interferon signaling pathway

(2020) Jin-Yan Li et al.   VIRUS RESEARCH

SARS-CoV-2 ORF3b Is a Potent Interferon Antagonist Whose Activity Is Increased by a Naturally Occurring Elongation Variant

(2020) Yoriyuki Konno et al.   Cell Reports

Prohibitins: A Critical Role in Mitochondrial Functions and Implication in Diseases

(2019) Anna Signorile et al.   Cells

The stress granule protein G3BP1 binds viral dsRNA and RIG-I to enhance IFN-β response

(2019) Susana Soo-Yeon Kim et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Coronavirus envelope protein: current knowledge

(2019) Dewald Schoeman et al.   Virology Journal

G3BP1 and G3BP2 regulate translation of interferon-stimulated genes: IFITM1, IFITM2 and IFITM3 in the cancer cell line MCF7

(2019) Umber Alam et al.   MOLECULAR AND CELLULAR BIOCHEMISTRY

Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors

(2019) Robert N. Kirchdoerfer et al.   Nature Communications

Nucleocapsid protein recruitment to replication-transcription complexes plays a crucial role in coronaviral life cycle

(2019) Yingying Cong et al.   JOURNAL OF VIROLOGY

Nsp3 of coronaviruses: Structures and functions of a large multi-domain protein

(2018) Jian Lei et al.   ANTIVIRAL RESEARCH

Structural model of the SARS coronavirus E channel in LMPG micelles

(2018) Wahyu Surya et al.   BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES

The essential role of mitochondrial dynamics in antiviral immunity

(2018) Seong-Jun Kim et al.   MITOCHONDRION

An “Old” protein with a new story: Coronavirus endoribonuclease is important for evading host antiviral defenses

(2018) Xufang Deng et al.   VIROLOGY

Structural and biochemical characterization of endoribonuclease Nsp15 encoded by Middle East respiratory syndrome coronavirus

(2018) Lianqi Zhang et al.   JOURNAL OF VIROLOGY

Origin and evolution of pathogenic coronaviruses

(2018) Jie Cui et al.   NATURE REVIEWS MICROBIOLOGY

Dynamin-related protein 1 has membrane constricting and severing abilities sufficient for mitochondrial and peroxisomal fission

(2018) Sukrut C. Kamerkar et al.   Nature Communications

Structure and Function of Viral Deubiquitinating Enzymes

(2017) Ben A. Bailey-Elkin et al.   JOURNAL OF MOLECULAR BIOLOGY

Structural Analysis of Porcine Reproductive and Respiratory Syndrome Virus Non-structural Protein 7α (NSP7α) and Identification of Its Interaction with NSP9

(2017) Jiaping Chen et al.   Frontiers in Microbiology

Dengue Virus Perturbs Mitochondrial Morphodynamics to Dampen Innate Immune Responses

(2016) Laurent Chatel-Chaix et al.   Cell Host & Microbe

The changing landscape of membrane protein structural biology through developments in electron microscopy

(2016) Shaun Rawson et al.   MOLECULAR MEMBRANE BIOLOGY

The Conserved Coronavirus Macrodomain Promotes Virulence and Suppresses the Innate Immune Response during Severe Acute Respiratory Syndrome Coronavirus Infection

(2016) Anthony R. Fehr et al.   mBio

Structure, Function, and Evolution of Coronavirus Spike Proteins

(2016) Fang Li   Annual Review of Virology

Multifaceted role of prohibitin in cell survival and apoptosis

(2015) Ya-Ting Peng et al.   APOPTOSIS

Middle East Respiratory Syndrome Coronavirus: Another Zoonotic Betacoronavirus Causing SARS-Like Disease

(2015) Jasper F. W. Chan et al.   CLINICAL MICROBIOLOGY REVIEWS

Transmembrane serine protease TMPRSS2 activates hepatitis C virus infection

(2015) Mariko Esumi et al.   HEPATOLOGY

Structural Insights into Mitochondrial Antiviral Signaling Protein (MAVS)-Tumor Necrosis Factor Receptor-associated Factor 6 (TRAF6) Signaling

(2015) Zhubing Shi et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Severe Acute Respiratory Syndrome Coronavirus ORF7a Inhibits Bone Marrow Stromal Antigen 2 Virion Tethering through a Novel Mechanism of Glycosylation Interference

(2015) Justin K. Taylor et al.   JOURNAL OF VIROLOGY

Coronavirus nonstructural protein 1: Common and distinct functions in the regulation of host and viral gene expression

(2015) Krishna Narayanan et al.   VIRUS RESEARCH

Host cell proteases: Critical determinants of coronavirus tropism and pathogenesis

(2015) Jean Kaoru Millet et al.   VIRUS RESEARCH

Inferring the hosts of coronavirus using dual statistical models based on nucleotide composition

(2015) Qin Tang et al.   Scientific Reports

How RIG-I like receptors activate MAVS

(2015) Bin Wu et al.   Current Opinion in Virology

Severe acute respiratory syndrome coronavirus protein 6 mediates ubiquitin-dependent proteosomal degradation of N-Myc (and STAT) interactor

(2015) Weijia Cheng et al.   VIROLOGICA SINICA

Accessory proteins of SARS-CoV and other coronaviruses

(2014) Ding Xiang Liu et al.   ANTIVIRAL RESEARCH

The SARS coronavirus nucleocapsid protein – Forms and functions

(2014) Chung-ke Chang et al.   ANTIVIRAL RESEARCH

The SARS-coronavirus membrane protein induces apoptosis via interfering with PDK1–PKB/Akt signalling

(2014) Ho Tsoi et al.   BIOCHEMICAL JOURNAL

CoronavirusNsp10, a Critical Co-factor for Activation of Multiple Replicative Enzymes

(2014) Mickaël Bouvet et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

SARS-Coronavirus Open Reading Frame-9b Suppresses Innate Immunity by Targeting Mitochondria and the MAVS/TRAF3/TRAF6 Signalosome

(2014) Chong-Shan Shi et al.   JOURNAL OF IMMUNOLOGY

The Host Protease TMPRSS2 Plays a Major Role in In Vivo Replication of Emerging H7N9 and Seasonal Influenza Viruses

(2014) K. Sakai et al.   JOURNAL OF VIROLOGY

Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein

(2014) Jean Kaoru Millet et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Membrane rearrangements mediated by coronavirus nonstructural proteins 3 and 4

(2014) Marne C. Hagemeijer et al.   VIROLOGY

The Coronavirus Nucleocapsid Is a Multifunctional Protein

(2014) Ruth McBride et al.   Viruses-Basel

Characterization of a Critical Interaction between the Coronavirus Nucleocapsid Protein and Nonstructural Protein 3 of the Viral Replicase-Transcriptase Complex

(2013) K. R. Hurst et al.   JOURNAL OF VIROLOGY

TMPRSS2 and ADAM17 Cleave ACE2 Differentially and Only Proteolysis by TMPRSS2 Augments Entry Driven by the Severe Acute Respiratory Syndrome Coronavirus Spike Protein

(2013) A. Heurich et al.   JOURNAL OF VIROLOGY

Middle East Respiratory Syndrome Coronavirus (MERS-CoV): Announcement of the Coronavirus Study Group

(2013) R. J. de Groot et al.   JOURNAL OF VIROLOGY

Severe Acute Respiratory Syndrome Coronavirus Nonstructural Proteins 3, 4, and 6 Induce Double-Membrane Vesicles

(2013) M. M. Angelini et al.   mBio

MAVS recruits multiple ubiquitin E3 ligases to activate antiviral signaling cascades

(2013) Siqi Liu et al.   eLife

Severe Acute Respiratory Syndrome Coronavirus Protein nsp1 Is a Novel Eukaryotic Translation Inhibitor That Represses Multiple Steps of Translation Initiation

(2012) K. G. Lokugamage et al.   JOURNAL OF VIROLOGY

Discovery of Seven Novel Mammalian and Avian Coronaviruses in the Genus Deltacoronavirus Supports Bat Coronaviruses as the Gene Source of Alphacoronavirus and Betacoronavirus and Avian Coronaviruses as the Gene Source of Gammacoronavirus and Deltacoronavirus

(2012) P. C. Y. Woo et al.   JOURNAL OF VIROLOGY

HIV-1, ubiquitin and ubiquitin-like proteins: the dialectic interactions of a virus with a sophisticated network of post-translational modifications

(2011) Martine Biard-Piechaczyk et al.   BIOLOGY OF THE CELL

Biochemical and Structural Insights into the Mechanisms of SARS Coronavirus RNA Ribose 2′-O-Methylation by nsp16/nsp10 Protein Complex

(2011) Yu Chen et al.   PLoS Pathogens

SARS Coronavirus nsp1 Protein Induces Template-Dependent Endonucleolytic Cleavage of mRNAs: Viral mRNAs Are Resistant to nsp1-Induced RNA Cleavage

(2011) Cheng Huang et al.   PLoS Pathogens

A structural analysis of M protein in coronavirus assembly and morphology

(2010) Benjamin W. Neuman et al.   JOURNAL OF STRUCTURAL BIOLOGY

Deubiquitinating and Interferon Antagonism Activities of Coronavirus Papain-Like Proteases

(2010) M. A. Clementz et al.   JOURNAL OF VIROLOGY

Interactions of SARS Coronavirus Nucleocapsid Protein with the host cell proteasome subunit p42

(2010) Qin Wang et al.   Virology Journal

Coronavirus Genomics and Bioinformatics Analysis

(2010) Patrick C. Y. Woo et al.   Viruses-Basel

In Vitro Reconstitution of SARS-Coronavirus mRNA Cap Methylation

(2010) Mickaël Bouvet et al.   PLoS Pathogens

Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing

(2010) Lance D. Eckerle et al.   PLoS Pathogens

The ion channel activity of the SARS-coronavirus 3a protein is linked to its pro-apoptotic function

(2009) Chak-Ming Chan et al.   INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY

Severe Acute Respiratory Syndrome Coronavirus nsp9 Dimerization Is Essential for Efficient Viral Growth

(2009) Z. J. Miknis et al.   JOURNAL OF VIROLOGY

Severe Acute Respiratory Syndrome Coronavirus Papain-Like Protease Ubiquitin-Like Domain and Catalytic Domain Regulate Antagonism of IRF3 and NF- B Signaling

(2009) M. Frieman et al.   JOURNAL OF VIROLOGY

Severe Acute Respiratory Syndrome Coronavirus Nonstructural Protein 2 Interacts with a Host Protein Complex Involved in Mitochondrial Biogenesis and Intracellular Signaling

(2009) C. T. Cornillez-Ty et al.   JOURNAL OF VIROLOGY

Viral avoidance and exploitation of the ubiquitin system

(2009) Felix Randow et al.   NATURE CELL BIOLOGY

A two-pronged strategy to suppress host protein synthesis by SARS coronavirus Nsp1 protein

(2009) Wataru Kamitani et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Functional screen reveals SARS coronavirus nonstructural protein nsp14 as a novel cap N7 methyltransferase

(2009) Y. Chen et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Mutagenesis of the transmembrane domain of the SARS coronavirus spike glycoprotein: refinement of the requirements for SARS coronavirus cell entry

(2009) Jeroen Corver et al.   Virology Journal

Structure and Inhibition of the SARS Coronavirus Envelope Protein Ion Channel

(2009) Konstantin Pervushin et al.   PLoS Pathogens

ISG15 Inhibits Nedd4 Ubiquitin E3 Activity and Enhances the Innate Antiviral Response

(2008) Oxana A. Malakhova et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Glycogen Synthase Kinase-3 Regulates the Phosphorylation of Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein and Viral Replication

(2008) Chia-Hsin Wu et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Multiple Nucleic Acid Binding Sites and Intrinsic Disorder of Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein: Implications for Ribonucleocapsid Protein Packaging

(2008) C.-K. Chang et al.   JOURNAL OF VIROLOGY

The M, E, and N Structural Proteins of the Severe Acute Respiratory Syndrome Coronavirus Are Required for Efficient Assembly, Trafficking, and Release of Virus-Like Particles

(2008) Y. L. Siu et al.   JOURNAL OF VIROLOGY

The Transmembrane Domain of the Severe Acute Respiratory Syndrome Coronavirus ORF7b Protein Is Necessary and Sufficient for Its Retention in the Golgi Complex

(2008) S. R. Schaecher et al.   JOURNAL OF VIROLOGY

Cathepsin L Functionally Cleaves the Severe Acute Respiratory Syndrome Coronavirus Class I Fusion Protein Upstream of Rather than Adjacent to the Fusion Peptide

(2008) B. J. Bosch et al.   JOURNAL OF VIROLOGY

Severe Acute Respiratory Syndrome Coronavirus nsp1 Suppresses Host Gene Expression, Including That of Type I Interferon, in Infected Cells

(2008) K. Narayanan et al.   JOURNAL OF VIROLOGY

Proteomics Analysis Unravels the Functional Repertoire of Coronavirus Nonstructural Protein 3

(2008) B. W. Neuman et al.   JOURNAL OF VIROLOGY

The SARS-Coronavirus PLnc domain of nsp3 as a replication/transcription scaffolding protein

(2008) Isabelle Imbert et al.   VIRUS RESEARCH