In:
The Journal of Immunology, The American Association of Immunologists, Vol. 208, No. 1_Supplement ( 2022-05-01), p. 111.28-111.28
Abstract:
The outbreak of infectious severe and acute respiratory syndrome (SARS)-CoV-2 which induces coronavirus disease 19 (COVID-19) causes patients to develop acute respiratory distress syndrome (ARDS) and death by triggering uncontrolled immune responses. Dysregulated immune responses impair healthy organs by over-production of pro-inflammatory cytokines, which are called “cytokine storm”. In this study, an improved cell-permeable nuclear import inhibitor (iCP-NI) has been developed by fusing sequence-optimized advanced macromolecule transduction domains (aMTDs) and nuclear localization sequence (NLS) originated from human NF-κB to treat the cytokine storm mediated organ failure and death in COVID-19. Intracellularly delivered NLS inhibits the transport of various inflammation-associated transcription factors (IATFs) such as NF-κB, NFAT, AP-1 and STAT1/3 which results in suppressed expression of pro-inflammatory cytokines. In brief, iCP-NI decreased the lethality of RNA virus infection mimetic pneumonitis animals by protecting the lung structure from inflammation-mediated destruction via reduction of the inflammatory cytokines in the lung. Continuously, iCP-NI significantly attenuates the severity of the SARS-CoV-2 infected syrian hamster model. The inhibition of viral replication is proved with quantitative PCR by reducing the level of RdRp gene (log7.04 vs log5.79). Likewise, the levels of inflammatory cytokines such as TNF-α and IL-17A in the lungs are significantly decreased and thereby, the lung structures are protected from inflammation-mediated damages. As a result, the iCP-NI could be developed as a novel medicine to cure various inflammatory diseases including COVID-19.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.208.Supp.111.28
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2022
detail.hit.zdb_id:
1475085-5
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