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Targeting Polyamines Inhibits Coronavirus Infection by Reducing Cellular Attachment and Entry.
Firpo, Mason R; Mastrodomenico, Vincent; Hawkins, Grant M; Prot, Matthieu; Levillayer, Laura; Gallagher, Tom; Simon-Loriere, Etienne; Mounce, Bryan C.
  • Firpo MR; Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois 60153, United States.
  • Mastrodomenico V; Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois 60153, United States.
  • Hawkins GM; Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois 60153, United States.
  • Prot M; G5 Evolutionary Genomics of RNA Viruses, Institut Pasteur, Paris 75015, France.
  • Levillayer L; Functional Genetics of Infectious Diseases Unit, Institut Pasteur, Paris 75015, France.
  • Gallagher T; Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois 60153, United States.
  • Simon-Loriere E; G5 Evolutionary Genomics of RNA Viruses, Institut Pasteur, Paris 75015, France.
  • Mounce BC; Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois 60153, United States.
ACS Infect Dis ; 7(6): 1423-1432, 2021 06 11.
Article in English | MEDLINE | ID: covidwho-1026808
ABSTRACT
Coronaviruses first garnered widespread attention in 2002 when the severe acute respiratory syndrome coronavirus (SARS-CoV) emerged from bats in China and rapidly spread in human populations. Since then, Middle East respiratory syndrome coronavirus (MERS-CoV) emerged and still actively infects humans. The recent SARS-CoV-2 outbreak and the resulting disease (coronavirus disease 2019, COVID19) have rapidly and catastrophically spread and highlighted significant limitations to our ability to control and treat infection. Thus, a basic understanding of entry and replication mechanisms of coronaviruses is necessary to rationally evaluate potential antivirals. Here, we show that polyamines, small metabolites synthesized in human cells, facilitate coronavirus replication and the depletion of polyamines with FDA-approved molecules significantly reduces coronavirus replication. We find that diverse coronaviruses, including endemic and epidemic coronaviruses, exhibit reduced attachment and entry into polyamine-depleted cells. We further demonstrate that several molecules targeting the polyamine biosynthetic pathway are antiviral in vitro. In sum, our data suggest that polyamines are critical to coronavirus replication and represent a highly promising drug target in the current and any future coronavirus outbreaks.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Middle East Respiratory Syndrome Coronavirus / COVID-19 Type of study: Experimental Studies Limits: Humans Language: English Journal: ACS Infect Dis Year: 2021 Document Type: Article Affiliation country: Acsinfecdis.0c00491

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Middle East Respiratory Syndrome Coronavirus / COVID-19 Type of study: Experimental Studies Limits: Humans Language: English Journal: ACS Infect Dis Year: 2021 Document Type: Article Affiliation country: Acsinfecdis.0c00491