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Boschi, C.

Publications and source records attributed to Boschi, C..

4 recordsLinked to original sources

Five-year (2017-2022) evolutionary dynamics of human coronavirus OC43 in southern France based on whole genome next-generation sequencing

HCoV-OC43 genomes and their evolution are scarcely studied worldwide and in France with only 361 genomes available as of October 2023. Here we implemented an in-house PCR amplification system to obtain retrospectively by next-generation sequencing then analyze HCoV-OC43 genomes for infections diagnosed with this virus in southern France between 02/2017 and 10/2022. Multiplex PCR amplification using a set of in-house primers designed using the Gemi software was carried out on residues of HCoV-OC43 RNA-positive nasopharyngeal samples, before next-generation sequencing (NGS) using Illumina technology on a NovaSeq 6000 instrument. HCoV-OC43 genome assembly, bioinformatic analyses, and phylogeny reconstruction were then carried out using CLC Genomics, Mafft, BioEdit, Nextstrain, Nextclade, MEGA, iTOL and RDP4 softwares. A total of 34 PCR primer pairs were designed for amplification then NGS of HCoV-OC43 genomes. A total of 185 genomes were obtained, 17, 79 and 89 belonging to genotypes G, J and K, respectively. These three genotypes circulated exclusively or co-circulated according to the year. A total of 303, 940, and 1,300 amino acid substitutions were detected in genotype G, J and K, respectively, compared with reference genomes of the same genotype dating back to 2017-2018. Possible recombinations were detected for 10 HCoV-OC43 genomes classified in genotypes K or J. Overall, the present study more than doubled the set of HCoV-OC43 genomes available worldwide for the 2017-2022 period, and contributed to the monitoring of the HCoV-OC43 evolutionary dynamics.

microbiology↗

SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19 Morbidities and Therapeutics and for Vaccine Adverse Effects

Experimental findings for SARS-CoV-2 related to the glycan biochemistry of coronaviruses indicate that attachments from spike protein to glycoconjugates on the surfaces of red blood cells (RBCs), other blood cells and endothelial cells are key to the infectivity and morbidity of COVID-19. To provide further insight into these glycan attachments and their potential clinical relevance, the classic hemagglutination (HA) assay was applied using spike protein from the Wuhan, Alpha, Delta and Omicron B.1.1.529 lineages of SARS-CoV-2 mixed with human RBCs. The electrostatic potential of the central region of spike protein from these four lineages was studied through molecular modeling simulations. Inhibition of spike protein-induced HA was tested using the macrocyclic lactone ivermectin (IVM), which is indicated to bind strongly to SARS-CoV-2 spike protein glycan sites. The results of these experiments were, first, that spike protein from these four lineages of SARS-CoV-2 induced HA. Omicron induced HA at a significantly lower threshold concentration of spike protein than for the three prior lineages and was much more electropositive on its central spike protein region. IVM blocked HA when added to RBCs prior to spike protein and reversed HA when added afterwards. These results validate and extend prior findings on the role of glycan bindings of viral spike protein in COVID-19. They furthermore suggest therapeutic options using competitive glycan-binding agents such as IVM and may help elucidate rare serious adverse effects (AEs) associated with COVID-19 mRNA vaccines which use spike protein as the generated antigen.

biochemistry↗

Sequencing of Monkeypox virus from infected patients reveals viral genomes with APOBEC3-like editing, gene inactivation, and bacterial agents of skin superinfection

An epidemic of Monkeypox virus (MPX virus) infections has arisen in May 2022 in non-endemic countries particularly in Europe among men having sex with men, whose extent is unprecedented. Since May 2022 we implemented MPX virus diagnosis by real-time PCR at university hospitals of Marseille, southern France. Here, we performed DNA metagenomic analyses of clinical samples from MPX virus-infected patients between June and July 2022, using next-generation sequencing with Illumina or Nanopore technologies. Twenty-five samples from 25 patients were studied. This allowed obtaining a MPX virus genome for 18 patients, essentially from genital skin lesions and rectal swabbing. All 18 genomes were classified in the MPX virus B.1 lineage, and we delineated five sublineages (A-E). We detected a high number of mutations (66-73) scattered along the MPX virus genomes relatively to the genome obtained from a human in Nigeria in 2018. Some non-synonymous mutations occurred in genes encoding central proteins, among which transcription factors and core and envelope proteins. They included two mutations that truncate RNA polymerase subunit RPO132 and a phospholipase D-like protein, which suggests gene inactivation. In addition, we identified that a large majority of nucleotide substitutions (94%) in the 18 MPX virus genomes were G>A or C>T, suggesting the action of human APOBEC3 enzymes. Finally, while we did not detect reads matching with main bacterial agents of sexually transmitted infections, >1,000 reads identified Staphylococcus aureus and Streptococcus pyogenes for 7 and 17 samples, respectively. These findings warrant a close genomic monitoring of MPX virus to get a better picture of this virus genetic evolution and mutational patterns, and they point out the common presence in monkeypox lesions of bacterial agents of skin superinfection, which warrants a close clinical monitoring in monkeypox patients.

microbiology↗

Omicron variant escapes therapeutic mAbs contrary to eight prior main VOC

Monocolonal antibodies (mAbs) are currently used for active immunization of COVID-19 in immunocompromised patients. We herein show that in spite there are variations in susceptibility to available mAbs that are authorized for clinical use in France tested on the original B.1.1 virus and 9 variants of concern or of interest, the cocktail casirivimab/imdevimab (REGN-CoV-2) showed a major synergistic effect. However, none of the four mAbs either alone or in combination neutralized the new Omicron variant. Our data strongly warrant a reinforcement of protective measures against infection for immunocompromised patients.

microbiology↗