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Nucleolin mediates SARS-CoV-2 replication and viral-induced apoptosis of host cells.
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.
  • Merino VF; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: vmerino1@jhmi.edu.
  • Yan Y; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Ordonez AA; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: aordone2@jhmi.edu.
  • Bullen CK; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Lee A; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Saeki H; Department of Human Pathology, Faculty of Medicine, Juntendo University, Tokyo, Japan.
  • Ray K; Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA; Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
  • Huang T; Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Jain SK; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Pomper MG; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Antiviral Res ; 211: 105550, 2023 03.
Article in English | MEDLINE | ID: covidwho-2220438
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Prognostic study Topics: Variants Limits: Humans Language: English Journal: Antiviral Res Year: 2023 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Prognostic study Topics: Variants Limits: Humans Language: English Journal: Antiviral Res Year: 2023 Document Type: Article