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1.
Nucleic Acids Res ; 49(13): 7695-7712, 2021 07 21.
Article in English | MEDLINE | ID: covidwho-1298980

ABSTRACT

The multidomain non-structural protein 3 (Nsp3) is the largest protein encoded by coronavirus (CoV) genomes and several regions of this protein are essential for viral replication. Of note, SARS-CoV Nsp3 contains a SARS-Unique Domain (SUD), which can bind Guanine-rich non-canonical nucleic acid structures called G-quadruplexes (G4) and is essential for SARS-CoV replication. We show herein that the SARS-CoV-2 Nsp3 protein also contains a SUD domain that interacts with G4s. Indeed, interactions between SUD proteins and both DNA and RNA G4s were evidenced by G4 pull-down, Surface Plasmon Resonance and Homogenous Time Resolved Fluorescence. These interactions can be disrupted by mutations that prevent oligonucleotides from folding into G4 structures and, interestingly, by molecules known as specific ligands of these G4s. Structural models for these interactions are proposed and reveal significant differences with the crystallographic and modeled 3D structures of the SARS-CoV SUD-NM/G4 interaction. Altogether, our results pave the way for further studies on the role of SUD/G4 interactions during SARS-CoV-2 replication and the use of inhibitors of these interactions as potential antiviral compounds.


Subject(s)
COVID-19/virology , Coronavirus Papain-Like Proteases/metabolism , G-Quadruplexes , Protein Interaction Domains and Motifs , SARS-CoV-2 , Amino Acid Sequence , Coronavirus Papain-Like Proteases/chemistry , Humans , Ligands , Models, Molecular , Protein Binding , Protein Conformation , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , Spectrum Analysis , Structure-Activity Relationship , Virus Replication
2.
Nat Commun ; 12(1): 3025, 2021 05 21.
Article in English | MEDLINE | ID: covidwho-1237997

ABSTRACT

Assessment of the cumulative incidence of SARS-CoV-2 infections is critical for monitoring the course and extent of the COVID-19 epidemic. Here, we report estimated seroprevalence in the French population and the proportion of infected individuals who developed neutralising antibodies at three points throughout the first epidemic wave. Testing 11,000 residual specimens for anti-SARS-CoV-2 IgG and neutralising antibodies, we find nationwide seroprevalence of 0.41% (95% CI: 0.05-0.88) mid-March, 4.14% (95% CI: 3.31-4.99) mid-April and 4.93% (95% CI: 4.02-5.89) mid-May 2020. Approximately 70% of seropositive individuals have detectable neutralising antibodies. Infection fatality rate is 0.84% (95% CI: 0.70-1.03) and increases exponentially with age. These results confirm that the nationwide lockdown substantially curbed transmission and that the vast majority of the French population remained susceptible to SARS-CoV-2 in May 2020. Our study shows the progression of the first epidemic wave and provides a framework to inform the ongoing public health response as viral transmission continues globally.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , COVID-19/epidemiology , COVID-19/virology , Child , Child, Preschool , Epidemics , Female , France/epidemiology , Humans , Infant , Infant, Newborn , Male , Middle Aged , Prevalence , SARS-CoV-2/physiology , Seroepidemiologic Studies , Young Adult
3.
Eur J Immunol ; 51(1): 180-190, 2021 01.
Article in English | MEDLINE | ID: covidwho-1023283

ABSTRACT

Although the COVID-19 pandemic peaked in March/April 2020 in France, the prevalence of infection is barely known. Using high-throughput methods, we assessed herein the serological response against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of 1847 participants working in three sites of an institution in Paris conurbation. In May-July 2020, 11% (95% confidence interval [CI]: 9.7-12.6) of serums were positive for IgG against the SARS-CoV-2 N and S proteins, and 9.5% (95% CI: 8.2-11.0) were neutralizer in pseudo-typed virus assays. The prevalence of seroconversion was 11.6% (95% CI: 10.2-13.2) when considering positivity in at least one assay. In 5% of RT-qPCR positive individuals, no systemic IgGs were detected. Among immune individuals, 21% had been asymptomatic. Anosmia (loss of smell) and ageusia (loss of taste) occurred in 52% of the IgG-positive individuals and in 3% of the negative ones. In contrast, 30% of the anosmia-ageusia cases were seronegative, suggesting that the true prevalence of infection may have reached 16.6%. In sera obtained 4-8 weeks after the first sampling, anti-N and anti-S IgG titers and neutralization activity in pseudo-virus assay declined by 31%, 17%, and 53%, resulting thus in half-life of 35, 87, and 28 days, respectively. The population studied is representative of active workers in Paris. The short lifespan of the serological systemic responses suggests an underestimation of the true prevalence of infection.


Subject(s)
Antibodies, Viral/blood , COVID-19/blood , COVID-19/immunology , Adult , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/epidemiology , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Male , Pandemics , Paris/epidemiology , Seroepidemiologic Studies , Time Factors
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