scholarly journals A Recombinant Fragment of Human Surfactant Protein D Binds Spike Protein and Inhibits Infectivity and Replication of SARS-CoV-2 in Clinical Samples

2021 ◽  
Author(s):  
Taruna Madan ◽  
Barnali Biswas ◽  
Praveen M. Varghese ◽  
Rambhadur Subedi ◽  
Hrishikesh Pandit ◽  
...  
Keyword(s):  
Surfactant Protein ◽  
Spike Protein ◽  
Clinical Samples ◽  
Surfactant Protein D ◽  
Recombinant Fragment

scholarly journals A recombinant fragment of Human surfactant protein D binds Spike protein and inhibits infectivity and replication of SARS-CoV-2 in clinical samples

2020 ◽  
Author(s):  
Taruna Madan ◽  
Barnali Biswas ◽  
Praveen M. Varghese ◽  
Rambhadur Subedi ◽  
Hrishikesh Pandit ◽  
...  
Keyword(s):  
Immune Surveillance ◽  
Cell Receptor ◽  
Surfactant Protein ◽  
Spike Protein ◽  
Clinical Samples ◽  
Surfactant Protein D ◽  
Amino Acid Residues ◽  
Recombinant Fragment ◽  
Acute Infectious Disease

AbstractRationaleCOVID-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.ObjectiveThis 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.MethodsrfhSP-D interaction 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.Measurements and Main ResultsIn-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 5μM 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 5μM rfhSP-D.ConclusionsThese 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.

scholarly journals A Recombinant Fragment of Human Surfactant Protein D Lacking the Short Collagen-Like Stalk Fails to Correct Morphological Alterations in Lungs of SP-D Deficient Mice

2009 ◽  
Vol 292 (2) ◽  
pp. 183-189 ◽  
Author(s):  
Lars Knudsen ◽  
Katharina Wucherpfennig ◽  
Rose-Marie Mackay ◽  
Paul Townsend ◽  
Christian Mühlfeld ◽  
...  
Keyword(s):  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Recombinant Fragment ◽  
Morphological Alterations ◽  
Deficient Mice

Protective effects of a recombinant fragment of human surfactant protein D in a murine model of pulmonary hypersensitivity induced by dust mite allergens

2003 ◽  
Vol 86 (3) ◽  
pp. 299-307 ◽  
Author(s):  
Mamta Singh ◽  
Taruna Madan ◽  
Patrick Waters ◽  
Shreemanta K. Parida ◽  
P.Usha Sarma ◽  
...  
Keyword(s):  
Murine Model ◽  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Protective Effects ◽  
Recombinant Fragment ◽  
Dust Mite

Surfactant protein D increases phagocytosis and aggregation of pollen-allergen starch granules

2005 ◽  
Vol 288 (4) ◽  
pp. L692-L698 ◽  
Author(s):  
Veit J. Erpenbeck ◽  
Delphine C. Malherbe ◽  
Stefanie Sommer ◽  
Andreas Schmiedl ◽  
Wolfram Steinhilber ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Allergic Inflammation ◽  
Allergic Airway Inflammation ◽  
Surfactant Protein ◽  
Phleum Pratense ◽  
Surfactant Protein D ◽  
Starch Granules ◽  
Recombinant Fragment ◽  
Surfactant Lipid ◽  
Induced Aggregation

Recent studies have shown that surfactant components, in particular the collectins surfactant protein (SP)-A and -D, modulate the phagocytosis of various pathogens by alveolar macrophages. This interaction might be important not only for the elimination of pathogens but also for the elimination of inhaled allergens and might explain anti-inflammatory effects of SP-A and SP-D in allergic airway inflammation. We investigated the effect of surfactant components on the phagocytosis of allergen-containing pollen starch granules (PSG) by alveolar macrophages. PSG were isolated from Dactylis glomerata or Phleum pratense, two common grass pollen allergens, and incubated with either rat or human alveolar macrophages in the presence of recombinant human SP-A, SP-A purified from patients suffering from alveolar proteinosis, a recombinant fragment of human SP-D, dodecameric recombinant rat SP-D, or the commercially available surfactant preparations Curosurf and Alveofact. Dodecameric rat recombinant SP-D enhanced binding and phagocytosis of the PSG by alveolar macrophages, whereas the recombinant fragment of human SP-D, SP-A, or the surfactant lipid preparations had no effect. In addition, recombinant rat SP-D bound to the surface of the PSG and induced aggregation. Binding, aggregation, and enhancement of phagocytosis by recombinant rat SP-D was completely blocked by EDTA and inhibited by d-maltose and to a lesser extent by d-galactose, indicating the involvement of the carbohydrate recognition domain of SP-D in these functions. The modulation of allergen phagocytosis by SP-D might play an important role in allergen clearance from the lung and thereby modulate the allergic inflammation of asthma.

scholarly journals Membrane Interactome of a Recombinant Fragment of Human Surfactant Protein D Reveals GRP78 as a Novel Binding Partner in PC3, a Metastatic Prostate Cancer Cell Line

2021 ◽  
Vol 11 ◽  
Author(s):  
Gargi Thakur ◽  
Gajanan Sathe ◽  
Indra Kundu ◽  
Barnali Biswas ◽  
Poonam Gautam ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Prostate Cancer Cell ◽  
Cancer Cell Line ◽  
Prostate Cancer Cell Line ◽  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Recombinant Fragment ◽  
Binding Partner

Surfactant protein-D (SP-D), a member of the collectin family has been shown to induce apoptosis in cancer cells. SP-D is composed of an N-terminal collagen-like domain and a calcium-dependent carbohydrate recognition domain (CRD). Recently, we reported that a recombinant fragment of human SP-D (rfhSP-D), composed of homotrimeric CRD region, induced intrinsic apoptotic pathway in prostate cancer cells. Here, we analyzed the membrane interactome of rfhSP-D in an androgen-independent prostate cancer cell line, PC3, by high resolution mass spectrometry and identified 347 proteins. Computational analysis of PPI network of this interactome in the context of prostate cancer metastasis and apoptosis revealed Glucose Regulated Protein of 78 kDa (GRP78) as an important binding partner of rfhSP-D. Docking studies suggested that rfhSP-D (CRD) bound to the substrate-binding domain of glycosylated GRP78. This was further supported by the observations that human recombinant GRP78 interfered with the binding of rfhSP-D to anti-SP-D polyclonal antibodies; GRP78 also significantly inhibited the binding of recombinant full-length human SP-D with a monoclonal antibody specific to the CRD in a dose-dependent manner. We conclude that the interaction with rfhSP-D is likely to interfere with the pro-survival signaling of GRP78.

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