Human Defensins Inhibit SARS-CoV-2 Infection by Blocking Viral Entry.

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101509722 Publication Model: Electronic Cited Medium: Internet ISSN: 1999-4915 (Electronic) Linking ISSN: 19994915 NLM ISO Abbreviation: Viruses Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI
    • Subject Terms:
      Defensins/*pharmacology ; SARS-CoV-2/*drug effects ; Virus Internalization/*drug effects; A549 Cells ; Caco-2 Cells ; Defensins/classification ; Epithelial Cells/virology ; HEK293 Cells ; HeLa Cells ; Humans ; SARS-CoV-2/physiology
    • Abstract:
      Innate immunity during acute infection plays a critical role in the disease severity of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and is likely to contribute to COVID-19 disease outcomes. Defensins are highly abundant innate immune factors in neutrophils and epithelial cells, including intestinal Paneth cells, and exhibit antimicrobial and immune-modulatory activities. In this study, we investigated the effects of human α- and β-defensins and RC101, a θ-defensin analog, on SARS-CoV-2 infection. We found that human neutrophil peptides (HNPs) 1-3, human defensin (HD) 5 and RC101 exhibited potent antiviral activity against pseudotyped viruses expressing SARS-CoV-2 spike proteins. HNP4 and HD6 had weak anti-SARS-CoV-2 activity, whereas human β-defensins (HBD2, HBD5 and HBD6) had no effect. HNP1, HD5 and RC101 also inhibited infection by replication-competent SARS-CoV-2 viruses and SARS-CoV-2 variants. Pretreatment of cells with HNP1, HD5 or RC101 provided some protection against viral infection. These defensins did not have an effect when provided post-infection, indicating their effect was directed towards viral entry. Indeed, HNP1 inhibited viral fusion but not the binding of the spike receptor-binding domain to hACE2. The anti-SARS-CoV-2 effect of defensins was influenced by the structure of the peptides, as linear unstructured forms of HNP1 and HD5 lost their antiviral function. Pro-HD5, the precursor of HD5, did not block infection by SARS-CoV-2. High virus titers overcame the effect of low levels of HNP1, indicating that defensins act on the virion. HNP1, HD5 and RC101 also blocked viral infection of intestinal and lung epithelial cells. The protective effects of defensins reported here suggest that they may be useful additives to the antivirus arsenal and should be thoroughly studied.
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    • Grant Information:
      R01 AI036478 United States AI NIAID NIH HHS; R01 AI129862 United States AI NIAID NIH HHS; 82030062 National Natural Science Foundation of China-Henan Joint Fund; R01AI36948, R01AI053668 National Institute of Allergy and Infectious Diseases; R01 AI053668 United States AI NIAID NIH HHS
    • Contributed Indexing:
      Keywords: SARS-CoV-2; antimicrobial peptides; defensins
    • Accession Number:
      0 (Defensins)
    • Publication Date:
      Date Created: 20210702 Date Completed: 20210715 Latest Revision: 20211130
    • Publication Date:
      20240105
    • Accession Number:
      PMC8310277
    • Accession Number:
      10.3390/v13071246
    • Accession Number:
      34206990