ABSTRACT
The global emergency caused by the SARS-CoV-2 pandemics can only be solved with adequate preventive and therapeutic strategies, both currently missing. The electropositive Receptor Binding Domain (RBD) of SARS-CoV-2 spike protein with abundant {beta}-sheet structure serves as target for COVID-19 therapeutic drug design. Here, we discovered that ultrathin 2D CuInP2S6 (CIPS) nanosheets as a new agent against SARS-CoV-2 infection, which also able to promote viral host elimination. CIPS exhibits extremely high and selective binding capacity with the RBD of SARS-CoV-2 spike protein, with consequent inhibition of virus entry and infection in ACE2-bearing cells and human airway epithelial organoids. CIPS displays nano-viscous properties in selectively binding with spike protein (KD < 1 pM) with negligible toxicity in vitro and in vivo. Further, the CIPS-bound SARS-CoV-2 was quickly phagocytosed and eliminated by macrophages, suggesting CIPS could be successfully used to capture and facilitate the virus host elimination with possibility of triggering anti-viral immunization. Thus, we propose CIPS as a promising nanodrug for future safe and effective anti-SARS-CoV-2 therapy, as well as for use as disinfection agent and surface coating material to constrain the SARS-CoV-2 spreading.
ABSTRACT
Macrophages are the main effector cells of innate immunity and are involved in inflammatory and anti-infective processes. They also have an essential role in maintaining tissue homeostasis, supporting tissue development, and repairing tissue damage. Until few years ago, it was believed that tissue macrophages derived from circulating blood monocytes, which terminally differentiated in the tissue and unable to proliferate. Recent evidence in the biology of tissue macrophages has uncovered a series of immune and ontogenic features that had been neglected for long, despite old observations. These include origin, heterogeneity, proliferative potential (or self-renewal), polarization, and memory. In recent years, the number of publications on tissue resident macrophages has grown rapidly, highlighting the renewed interest of the immunologists for these key players of innate immunity. This mini-review aims to summarizing the new current knowledge in macrophage immunobiology, in order to offer a clear and immediate overview of the field.
Subject(s)
Biology , Homeostasis , Immunity, Innate , Macrophages , Memory , Monocytes , Population CharacteristicsABSTRACT
Objective:To study the effects of andrographolide on the expression of IL-18 related cytokines by peripheral blood monocytes.Methods:After treatment of andrographolide in different concentrations on LPS stimulated human peripheral blood mononuclear cells (PBMC) and LPS+IFN-γ/IL-4 activated magnetic bead-sorted monocytes (PBM),the transcription level of IL-18,IL-18BP,IL-18Rα and IL-18Rβ was detected by real-time RT-PCR;and secreted IL-18,IL-18BP and IL-1β,IL-1Rα by PBM was detected with ELISA.Results:Andrographolide regulated the transcription of IL-18 and IL-18BP in a dose-and time-dependent effect.Andrographolide up-regulated the transcription of IL-18BP in LPS stimulated PBMC,and increased the ratio of IL-18BP/IL-18.The ratio of IL-18BP/IL-18 rose from 9.60 to 214 in LPS+IFNγ activated PBM,and IL-1Rα/IL-1β declined from 9 200 to 6 520 in IL-4 activated PBM by andrographolide treatment.Conclusion:Andrographolide can regulate IL-18 related gene transcription and expression in activated peripheral blood monocytes,and inhibit the excessive expression of IL-18 during inflammation.
