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10.1016/j.bioorg.2020.104619

http://scihub22266oqcxt.onion/10.1016/j.bioorg.2020.104619
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33450541!7784547!33450541
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suck abstract from ncbi


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pmid33450541      Bioorg+Chem 2021 ; 107 (ä): 104619
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  • Broad-spectrum antivirals of protoporphyrins inhibit the entry of highly pathogenic emerging viruses #MMPMID33450541
  • Lu S; Pan X; Chen D; Xie X; Wu Y; Shang W; Jiang X; Sun Y; Fan S; He J
  • Bioorg Chem 2021[Feb]; 107 (ä): 104619 PMID33450541show ga
  • Severe emerging and re-emerging viral infections such as Lassa fever, Avian influenza (AI), and COVID-19 caused by SARS-CoV-2 urgently call for new strategies for the development of broad-spectrum antivirals targeting conserved components in the virus life cycle. Viral lipids are essential components, and viral-cell membrane fusion is the required entry step for most unrelated enveloped viruses. In this paper, we identified a porphyrin derivative of protoporphyrin IX (PPIX) that showed broad antiviral activities in vitro against a panel of enveloped pathogenic viruses including Lassa virus (LASV), Machupo virus (MACV), and SARS-CoV-2 as well as various subtypes of influenza A viral strains with IC(50) values ranging from 0.91 +/- 0.25 muM to 1.88 +/- 0.34 muM. A mechanistic study using influenza A/Puerto Rico/8/34 (H1N1) as a testing strain showed that PPIX inhibits the infection in the early stage of virus entry through biophysically interacting with the hydrophobic lipids of enveloped virions, thereby inhibiting the entry of enveloped viruses into host cells. In addition, the preliminary antiviral activities of PPIX were further assessed by testing mice infected with the influenza A/Puerto Rico/8/34 (H1N1) virus. The results showed that compared with the control group without drug treatment, the survival rate and mean survival time of the mice treated with PPIX were apparently prolonged. These data encourage us to conduct further investigations using PPIX as a lead compound for the rational design of lipid-targeting antivirals for the treatment of infection with enveloped viruses.
  • |Animals[MESH]
  • |Antiviral Agents/chemical synthesis/metabolism/pharmacology/*therapeutic use[MESH]
  • |Arenaviruses, New World/drug effects[MESH]
  • |Chlorocebus aethiops[MESH]
  • |Dogs[MESH]
  • |Influenza A Virus, H1N1 Subtype/drug effects[MESH]
  • |Lassa virus/drug effects[MESH]
  • |Madin Darby Canine Kidney Cells[MESH]
  • |Male[MESH]
  • |Membrane Lipids/metabolism[MESH]
  • |Mice[MESH]
  • |Microbial Sensitivity Tests[MESH]
  • |Orthomyxoviridae Infections/*drug therapy[MESH]
  • |Protoporphyrins/chemical synthesis/metabolism/pharmacology/*therapeutic use[MESH]
  • |SARS-CoV-2/drug effects[MESH]
  • |Vero Cells[MESH]
  • |Viral Envelope/drug effects[MESH]


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