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Title: | Human Surfactant Protein D Binds Spike protein and acts as an entry inhibitor of SARS-CoV-2 Pseudotyped viral particles |
Authors: | Hsieh, M-H Beirag, N Murugaiah, V Chou, Y-C Kuo, W-S Kao, H-F Madan, T Kishore, U Wang, J-Y |
Keywords: | innate immunity;SARS-COV-2;spike protein;angiotensin converting enzyme 2;human pulmonary collectins;Surfactant Protein D |
Issue Date: | 14-May-2021 |
Publisher: | Frontiers Media |
Citation: | Hsieh, M.-H., Beirag, N., Murugaiah, V., Chou, Y.-C., Kuo, W.-S., Kao, H.-F., Madan, T., Kishore, U. and Wang, J.-Y. (2021) 'Human Surfactant Protein D Binds Spike Protein and Acts as an Entry Inhibitor of SARS-CoV-2 Pseudotyped Viral Particles', Frontiers in Immunology, 12, 641360, pp. 1 - 11. doi: 10.3389/fimmu.2021.641360. |
Abstract: | Copyright © 2021 Hsieh, Beirag, Murugaiah, Chou, Kuo, Kao, Madan, Kishore and Wang. Human SP-D is a potent innate immune molecule whose presence at pulmonary mucosal surfaces allows its role in immune surveillance against pathogens. Higher levels of serum SP-D have been reported in the patients with severe acute respiratory syndrome coronavirus (SARS-CoV). Studies have suggested the ability of human SP-D to recognise spike glycoprotein of SARS-CoV; its interaction with HCoV-229E strain leads to viral inhibition in human bronchial epithelial (16HBE) cells. Previous studies have reported that a recombinant fragment of human SP-D (rfhSP-D) composed of 8 Gly-X-Y repeats, neck and CRD region, can act against a range of viral pathogens including influenza A Virus and Respiratory Syncytial Virus in vitro, in vivo and ex vivo. In this context, this study was aimed at examining the likely protective role of rfhSP-D against SARS-CoV-2 infection. rfhSP-D showed a dose-responsive binding to S1 spike protein of SARS-CoV-2 and its receptor binding domain. Importantly, rfhSP-D inhibited interaction of S1 protein with the HEK293T cells overexpressing human angiotensin converting enzyme 2 (hACE2). The protective role of rfhSP-D against SARS-CoV-2 infection as an entry inhibitor was further validated by the use of pseudotyped lentiviral particles expressing SARS-CoV-2 S1 protein; ~0.5 RLU fold reduction in viral entry was seen following treatment with rfhSP-D (10 µg/ml). These results highlight the therapeutic potential of rfhSP-D in SARS-CoV-2 infection and merit pre-clinical studies in animal models. |
Description: | Data Availability Statement: The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. |
URI: | https://bura.brunel.ac.uk/handle/2438/22606 |
DOI: | https://doi.org/10.3389/fimmu.2021.641360 |
Other Identifiers: | 641360 |
Appears in Collections: | Dept of Life Sciences Research Papers |
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