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SARS CoV-2 Nucleoprotein Enhances the Infectivity of Lentiviral Spike Particles.
Mishra, Tarun; Sreepadmanabh, M; Ramdas, Pavitra; Sahu, Amit Kumar; Kumar, Atul; Chande, Ajit.
  • Mishra T; Molecular Virology Laboratory, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, India.
  • Sreepadmanabh M; Molecular Virology Laboratory, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, India.
  • Ramdas P; Molecular Virology Laboratory, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, India.
  • Sahu AK; Molecular Virology Laboratory, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, India.
  • Kumar A; Structural Biology Laboratory, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, India.
  • Chande A; Molecular Virology Laboratory, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, India.
Front Cell Infect Microbiol ; 11: 663688, 2021.
Article in English | MEDLINE | ID: covidwho-1221939
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ABSTRACT
The establishment of SARS CoV-2 spike-pseudotyped lentiviral (LV) systems has enabled the rapid identification of entry inhibitors and neutralizing agents, alongside allowing for the study of this emerging pathogen in BSL-2 level facilities. While such frameworks recapitulate the cellular entry process in ACE2+ cells, they are largely unable to factor in supplemental contributions by other SARS CoV-2 genes. To address this, we performed an unbiased ORF screen and identified the nucleoprotein (N) as a potent enhancer of spike-pseudotyped LV particle infectivity. We further demonstrate that the spike protein is better enriched in virions when the particles are produced in the presence of N protein. This enrichment of spike renders LV particles more infectious as well as less vulnerable to the neutralizing effects of a human IgG-Fc fused ACE2 microbody. Importantly, this improvement in infectivity is observed with both wild-type spike protein as well as the D614G mutant. Our results hold important implications for the design and interpretation of similar LV pseudotyping-based studies.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Severe acute respiratory syndrome-related coronavirus / COVID-19 Limits: Humans Language: English Journal: Front Cell Infect Microbiol Year: 2021 Document Type: Article Affiliation country: Fcimb.2021.663688

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Severe acute respiratory syndrome-related coronavirus / COVID-19 Limits: Humans Language: English Journal: Front Cell Infect Microbiol Year: 2021 Document Type: Article Affiliation country: Fcimb.2021.663688