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PIKfyve-specific inhibitors restrict replication of multiple coronaviruses in vitro but not in a murine model of COVID-19.
Logue, James; Chakraborty, Arup R; Johnson, Robert; Goyal, Girija; Rodas, Melissa; Taylor, Louis J; Baracco, Lauren; McGrath, Marisa E; Haupt, Robert; Furlong, Brooke A; Soong, Mercy; Prabhala, Pranav; Horvath, Viktor; Carlson, Kenneth E; Weston, Stuart; Ingber, Donald E; DePamphilis, Melvin L; Frieman, Matthew B.
  • Logue J; Department of Microbiology and Immunology, University of Maryland, School of Medicine, 685 West Baltimore St, Baltimore, MD, 21201, USA.
  • Chakraborty AR; Center for Pathogen Research, University of Maryland, School of Medicine, 685 West Baltimore St, Baltimore, MD, 21201, USA.
  • Johnson R; Division of Developmental Biology, National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, MD, 20892-2790, USA.
  • Goyal G; Department of Microbiology and Immunology, University of Maryland, School of Medicine, 685 West Baltimore St, Baltimore, MD, 21201, USA.
  • Rodas M; Center for Pathogen Research, University of Maryland, School of Medicine, 685 West Baltimore St, Baltimore, MD, 21201, USA.
  • Taylor LJ; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.
  • Baracco L; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.
  • McGrath ME; Department of Microbiology and Immunology, University of Maryland, School of Medicine, 685 West Baltimore St, Baltimore, MD, 21201, USA.
  • Haupt R; Center for Pathogen Research, University of Maryland, School of Medicine, 685 West Baltimore St, Baltimore, MD, 21201, USA.
  • Furlong BA; Department of Microbiology and Immunology, University of Maryland, School of Medicine, 685 West Baltimore St, Baltimore, MD, 21201, USA.
  • Soong M; Center for Pathogen Research, University of Maryland, School of Medicine, 685 West Baltimore St, Baltimore, MD, 21201, USA.
  • Prabhala P; Department of Microbiology and Immunology, University of Maryland, School of Medicine, 685 West Baltimore St, Baltimore, MD, 21201, USA.
  • Horvath V; Center for Pathogen Research, University of Maryland, School of Medicine, 685 West Baltimore St, Baltimore, MD, 21201, USA.
  • Carlson KE; Department of Microbiology and Immunology, University of Maryland, School of Medicine, 685 West Baltimore St, Baltimore, MD, 21201, USA.
  • Weston S; Center for Pathogen Research, University of Maryland, School of Medicine, 685 West Baltimore St, Baltimore, MD, 21201, USA.
  • Ingber DE; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.
  • DePamphilis ML; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.
  • Frieman MB; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.
Commun Biol ; 5(1): 808, 2022 08 12.
Article in English | MEDLINE | ID: covidwho-1991682
ABSTRACT
The ongoing COVID-19 pandemic has claimed more than 6 million lives and continues to test the world economy and healthcare systems. To combat this pandemic, the biological research community has shifted efforts to the development of medical countermeasures, including vaccines and therapeutics. However, to date, the only small molecules approved for the treatment of COVID-19 in the United States are the nucleoside analogue Remdesivir and the protease inhibitor Paxlovid, though multiple compounds have received Emergency Use Authorization and many more are currently being tested in human efficacy trials. One such compound, Apilimod, is being considered as a COVID-19 therapeutic in a Phase II efficacy trial. However, at the time of writing, there are no published efficacy data in human trials or animal COVID-19 models. Here we show that, while Apilimod and other PIKfyve inhibitors have potent antiviral activity in various cell lines against multiple human coronaviruses, these compounds worsen disease in a COVID-19 murine model when given prophylactically or therapeutically.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Drug Treatment Type of study: Randomized controlled trials Topics: Vaccines Limits: Animals / Humans Language: English Journal: Commun Biol Year: 2022 Document Type: Article Affiliation country: S42003-022-03766-2

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Drug Treatment Type of study: Randomized controlled trials Topics: Vaccines Limits: Animals / Humans Language: English Journal: Commun Biol Year: 2022 Document Type: Article Affiliation country: S42003-022-03766-2