Nucleolin mediates SARS-CoV-2 replication and viral-induced apoptosis of host cells

Host-oriented antiviral therapeutics are promising treatment options to combat COVID-19 and its emerging variants. However, relatively little is known about the cellular proteins hijacked by SARS-CoV-2 for its replication. Here we show that SARS-CoV-2 induces expression and cytoplasmic translocation...

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Bibliographic Details
Published in:Antiviral research 2023-03, Vol.211, p.105550-105550, Article 105550
Main Authors: Merino, Vanessa F., Yan, Yu, Ordonez, Alvaro A., Bullen, C. Korin, Lee, Albert, Saeki, Harumi, Ray, Krishanu, Huang, Tao, Jain, Sanjay K., Pomper, Martin G.
Format: Article
Language:English
Subjects:
Apoptosis
Aptamer
COVID
COVID-19
DNA Helicases
Humans
Nucleolin
Nucleoprotein
Phosphoproteins - metabolism
Poly-ADP-Ribose Binding Proteins
RNA Helicases - metabolism
RNA Recognition Motif Proteins
SARS-CoV-2
SARS-CoV-2 - metabolism
Virus Replication
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Summary:Host-oriented antiviral therapeutics are promising treatment options to combat COVID-19 and its emerging variants. However, relatively little is known about the cellular proteins hijacked by SARS-CoV-2 for its replication. Here we show that SARS-CoV-2 induces expression and cytoplasmic translocation of the nucleolar protein, nucleolin (NCL). NCL interacts with SARS-CoV-2 viral proteins and co-localizes with N-protein in the nucleolus and in stress granules. Knockdown of NCL decreases the stress granule component G3BP1, viral replication and improved survival of infected host cells. NCL mediates viral-induced apoptosis and stress response via p53. SARS-CoV-2 increases NCL expression and nucleolar size and number in lungs of infected hamsters. Inhibition of NCL with the aptamer AS-1411 decreases viral replication and apoptosis of infected cells. These results suggest nucleolin as a suitable target for anti-COVID therapies. Mechanisms of nucleolin-mediated SARS-CoV-2 infection: 1. SARS-CoV-2 induces nucleolar to cytoplasmic translocation of nucleolin; In the cytoplasm, nucleolin interacts with the viral nucleoprotein and host G3BP1 in stress granules and increases viral proliferation via a direct increase in translation of replication proteins such as G3BP1 (2), nucleoprotein and RdRp (3); Nucleolin mediates viral-induction of apoptosis (4) and cell cycle arrest (5) via stimulation of p53 and Rb. [Display omitted]
ISSN:0166-3542
1872-9096
DOI:10.1016/j.antiviral.2023.105550