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A Recombinant Fragment of Human Surfactant Protein D Binds Spike Protein and Inhibits Infectivity and Replication of SARS-CoV-2 in Clinical Samples.
Madan, Taruna; Biswas, Barnali; Varghese, Praveen M; Subedi, Rambhadur; Pandit, Hrishikesh; Idicula-Thomas, Susan; Kundu, Indra; Rooge, Sheetalnath; Agarwal, Reshu; Tripathi, Dinesh M; Kaur, Savneet; Gupta, Ekta; Gupta, Sanjeev K; Kishore, Uday.
  • Madan T; Department of Innate Immunity, and.
  • Biswas B; Department of Innate Immunity, and.
  • Varghese PM; Biosciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge, United Kingdom.
  • Subedi R; School of Biosciences and Technology, Vellore Institute of Technology, Vellore, India.
  • Pandit H; Department of Innate Immunity, and.
  • Idicula-Thomas S; Department of Innate Immunity, and.
  • Kundu I; Biomedical Informatics Centre, ICMR-National Institute for Research in Reproductive Health, Mumbai, India.
  • Rooge S; Biomedical Informatics Centre, ICMR-National Institute for Research in Reproductive Health, Mumbai, India.
  • Agarwal R; Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, Delhi, India.
  • Tripathi DM; Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, Delhi, India.
  • Kaur S; Department of Virology, Institute of Liver and Biliary Sciences, Delhi, India; and.
  • Gupta E; Department of Virology, Institute of Liver and Biliary Sciences, Delhi, India; and.
  • Gupta SK; Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, Delhi, India.
  • Kishore U; Intrust Consulting, Mumbai, India.
Am J Respir Cell Mol Biol ; 65(1): 41-53, 2021 07.
Article in English | MEDLINE | ID: covidwho-1158161
Preprint
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ABSTRACT
Coronavirus disease (COVID-19) is an acute infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human SP-D (surfactant protein D) is known to interact with the spike protein of SARS-CoV, but its immune surveillance against SARS-CoV-2 is not known. The current 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 the spike protein of SARS-CoV-2 and human ACE-2 (angiotensin-converting enzyme 2) receptor was predicted via docking analysis. The inhibition of interaction between the 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 assessed by measuring the expression of RdRp gene of the virus using quantitative PCR. In silico interaction studies indicated that three amino acid residues in the receptor-binding domain of spike protein 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; symptomatic, n = 8) and negative control samples (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) in Vero cells. An approximately two-fold reduction in viral infectivity was also observed after treatment with 1.67 µM rfhSP-D. These results conclusively demonstrate that the rfhSP-D mediated calcium independent interaction 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 significantly reduced SARS-CoV-2 infection and replication in vitro.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Virus Replication / Pulmonary Surfactant-Associated Protein D / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 Type of study: Observational study / Prognostic study Limits: Adult / Animals / Female / Humans / Male Language: English Journal: Am J Respir Cell Mol Biol Journal subject: Molecular Biology Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Virus Replication / Pulmonary Surfactant-Associated Protein D / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 Type of study: Observational study / Prognostic study Limits: Adult / Animals / Female / Humans / Male Language: English Journal: Am J Respir Cell Mol Biol Journal subject: Molecular Biology Year: 2021 Document Type: Article