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Title: | A recombinant fragment of Human surfactant protein D binds Spike protein and inhibits infectivity and replication of SARS-CoV-2 in clinical samples |
Authors: | Madan, T Biswas, B Varghese, PM Subedi, R Pandit, H Idicula-Thomas, S Kundu, I Rooge, S Agarwal, R Tripathi, DM Kaur, S Gupta, E Gupta, SK Kishore, U |
Keywords: | surfactant protein D;SARS-CoV-2;COVID-19;spike protein;entry inhibition |
Issue Date: | 30-Mar-2021 |
Publisher: | American Thoracic Society |
Citation: | Madan, T., Biswas, B., Varghese, P.M., Subedi, R., Pandit, H., Idicula-Thomas, S., Kundu, I., Rooge, S.B., Aggarwal, R., Tripathi, D., Kaur, S. (2021) 'A recombinant fragment of Human surfactant protein D binds Spike protein and inhibits infectivity and replication of SARS-CoV-2 in clinical samples', American Journal of Respiratory Cell and Molecular Biology, 65 (1), pp. 41-53. doi: 10.1165/rcmb.2021-0005OC. |
Abstract: | COVID -19 is an acute infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Human surfactant protein D (SP-D) is known to interact with spike protein of SARS-CoV, but its immune-surveillance against SARS-CoV-2 is not known. The study aimed to examine the potential of a recombinant fragment of human SP-D (rfhSP-D) as an inhibitor of replication and infection of SARS-CoV-2. The interaction of rfhSP-D with spike protein of SARS-CoV-2 and hACE-2 receptor was predicted via docking analysis. The inhibition of interaction between spike protein and ACE-2 by rfhSP-D was confirmed using direct and indirect ELISA. The effect of rfhSP-D on replication and infectivity of SARS-CoV-2 from clinical samples was studied by measuring the expression of RdRp gene of the virus using qPCR. In-silico interaction studies indicated that three amino acid residues in the RBD of spike of SARS-CoV-2 were commonly involved in interacting with rfhSP-D and ACE-2. Studies using clinical samples of SARS-CoV-2 positive cases (asymptomatic, n=7 and symptomatic, n=8 and negative controls n=15) demonstrated that treatment with 1.67 µM rfhSP-D inhibited viral replication by ~5.5 fold and was more efficient than Remdesivir (100 µM). Approximately, a 2-fold reduction in viral infectivity was also observed after treatment with 1.67 µM rfhSP-D. These results conclusively demonstrate that the calcium independent rfhSP-D mediated inhibition of binding between the receptor binding domain of the S1 subunit of the SARS-CoV-2 spike protein and human ACE-2, its host cell receptor, and a significant reduction in SARS-CoV-2 infection and replication in-vitro. |
URI: | https://bura.brunel.ac.uk/handle/2438/22513 |
DOI: | https://doi.org/10.1165/rcmb.2021-0005OC |
ISSN: | 1044-1549 |
Appears in Collections: | Brunel Library Dept of Life Sciences Research Papers |
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