Targeting intracellular Neu1 for coronavirus infection treatment

Darong Yang; Yin Wu; Isaac Turan; Joseph Keil; Kui Li; Michael H. Chen; Runhua Liu; Lizhong Wang; Xue-Long Sun; Guo-Yun Chen

iScience (Feb 2023)

Targeting intracellular Neu1 for coronavirus infection treatment

Darong Yang,
Yin Wu,
Isaac Turan,
Joseph Keil,
Kui Li,
Michael H. Chen,
Runhua Liu,
Lizhong Wang,
Xue-Long Sun,
Guo-Yun Chen

Affiliations

Darong Yang: Children’s Foundation Research Institute at Le Bonheur Children’s Hospital, Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103, USA
Yin Wu: Children’s Foundation Research Institute at Le Bonheur Children’s Hospital, Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103, USA
Isaac Turan: Department of Chemistry, Chemical and Biomedical Engineering and Center for Gene Regulation of Health and Disease (GRHD), Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44115, USA
Joseph Keil: Department of Chemistry, Chemical and Biomedical Engineering and Center for Gene Regulation of Health and Disease (GRHD), Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44115, USA
Kui Li: Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38103, USA
Michael H. Chen: Children’s Foundation Research Institute at Le Bonheur Children’s Hospital, Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103, USA
Runhua Liu: Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35233, USA; Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35233, USA
Lizhong Wang: Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35233, USA; Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35233, USA
Xue-Long Sun: Department of Chemistry, Chemical and Biomedical Engineering and Center for Gene Regulation of Health and Disease (GRHD), Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44115, USA; Corresponding author
Guo-Yun Chen: Children’s Foundation Research Institute at Le Bonheur Children’s Hospital, Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103, USA; Corresponding author

Journal volume & issue: Vol. 26, no. 2
p. 106037

Abstract

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Summary: There are currently no effective therapies for COVID-19 or antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and vaccines appear less effective against new SARS-CoV-2 variants; thus, there is an urgent need to understand better the virulence mechanisms of SARS-CoV-2 and the host response to develop therapeutic agents. Herein, we show that host Neu1 regulates coronavirus replication by controlling sialylation on coronavirus nucleocapsid protein. Coronavirus nucleocapsid proteins in COVID-19 patients and in coronavirus HCoV-OC43-infected cells were heavily sialylated; this sialylation controlled the RNA-binding activity and replication of coronavirus. Neu1 overexpression increased HCoV-OC43 replication, whereas Neu1 knockdown reduced HCoV-OC43 replication. Moreover, a newly developed Neu1 inhibitor, Neu5Ac2en-OAcOMe, selectively targeted intracellular sialidase, which dramatically reduced HCoV-OC43 and SARS-CoV-2 replication in vitro and rescued mice from HCoV-OC43 infection-induced death. Our findings suggest Neu1 inhibitors could be used to limit SARS-CoV-2 replication in patients with COVID-19, making Neu1 a potential therapeutic target for COVID-19 and future coronavirus pandemics.

classification description: virology

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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