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 Mani; Kaur, Simranpreet; Gupta, Ekta; Gupta, Sanjeev K.; Kishore, Uday

doi:10.1101/2020.12.18.423415

Cited by 4 publications

(1 citation statement)

References 33 publications

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“…The recombinant fragment of human lung surfactant protein D (rfhSP-D) is reported to be more potent than remdesivir, an antiviral, in inhibiting the replication and infectivity of SARS-CoV-2 and the activity is found to mediated through down regulation of RdRp gene expression ( Hsieh et al, 2021 ; Madan et al, 2021 ).…”

Section: Pulmonary Surfactants In Covid-19mentioning

confidence: 99%

The Role of Pulmonary Surfactants in the Treatment of Acute Respiratory Distress Syndrome in COVID-19

Wang

et al. 2021

Front. Pharmacol.

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Lung alveolar type-II (AT-II) cells produce pulmonary surfactant (PS), consisting of proteins and lipids. The lipids in PS are primarily responsible for reducing the air-fluid surface tension inside the alveoli of the lungs and to prevent atelectasis. The proteins are of two types: hydrophilic and hydrophobic. Hydrophilic surfactants are primarily responsible for opsonisation, thereby protecting the lungs from microbial and environmental contaminants. Hydrophobic surfactants are primarily responsible for respiratory function. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters the lungs through ACE-2 receptors on lungs and replicates in AT-II cells leading to the etiology of Coronavirus disease – 2019 (COVID-19). The SARS-CoV-2 virus damages the AT-II cells and results in decreased production of PS. The clinical symptoms of acute respiratory distress syndrome (ARDS) in COVID-19 patients are like those of neonatal respiratory distress syndrome (NRDS). The PS treatment is first-line treatment option for NRDS and found to be well tolerated in ARDS patients with inconclusive efficacy. Over the past 70°years, a lot of research is underway to produce natural/synthetic PS and developing systems for delivering PS directly to the lungs, in addition to finding the association between PS levels and respiratory illnesses. In the present COVID-19 pandemic situation, the scientific community all over the world is searching for the effective therapeutic options to improve the clinical outcomes. With a strong scientific and evidence-based background on role of PS in lung homeostasis and infection, few clinical trials were initiated to evaluate the functions of PS in COVID-19. Here, we connect the data on PS with reference to pulmonary physiology and infection with its possible therapeutic benefit in COVID-19 patients.

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Section: Pulmonary Surfactants In Covid-19mentioning

confidence: 99%

The Role of Pulmonary Surfactants in the Treatment of Acute Respiratory Distress Syndrome in COVID-19

Wang

et al. 2021

Front. Pharmacol.

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Inhalations with surfactant-BL in the late respiratory phase of COVID-19 in the patient with a severe course of the disease

Kudinova

Pasynkova²,

Аkimenko

2022

Tuberk. bolezni lëgk.

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The patient with severe viral-bacterial pneumonia and veriﬁed COVID-19 was successfully treated with surfactant therapy in the late respiratory phase of the disease, surfactant therapy was used to reduce the degree of hypoxemia and accelerate the weaning from non-invasive mechanical ventilation (NIMV). The native surfactant was administered with inhalations at the dose of 75 mg 2times a day on the 5th day of NIMV since SpO2 values persisted to be 92-93% and did not improve. Positive changes were observed after 4 inhalations: SpO2 reached 95% and then remained within the range of 94-97% with FiO2 90%. In total, the patient received 10 inhalations, then she was gradually transferred to breathing through an oronasal mask with humidiﬁed oxygen.

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SP-A and SP-D: Dual Functioning Immune Molecules With Antiviral and Immunomodulatory Properties

2021

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Surfactant proteins A (SP-A) and D (SP-D) are soluble innate immune molecules which maintain lung homeostasis through their dual roles as anti-infectious and immunomodulatory agents. SP-A and SP-D bind numerous viruses including influenza A virus, respiratory syncytial virus (RSV) and human immunodeficiency virus (HIV), enhancing their clearance from mucosal points of entry and modulating the inflammatory response. They also have diverse roles in mediating innate and adaptive cell functions and in clearing apoptotic cells, allergens and other noxious particles. Here, we review how the properties of these first line defense molecules modulate inflammatory responses, as well as host-mediated immunopathology in response to viral infections. Since SP-A and SP-D are known to offer protection from viral and other infections, if their levels are decreased in some disease states as they are in severe asthma and chronic obstructive pulmonary disease (COPD), this may confer an increased risk of viral infection and exacerbations of disease. Recombinant molecules of SP-A and SP-D could be useful in both blocking respiratory viral infection while also modulating the immune system to prevent excessive inflammatory responses seen in, for example, RSV or coronavirus disease 2019 (COVID-19). Recombinant SP-A and SP-D could have therapeutic potential in neutralizing both current and future strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus as well as modulating the inflammation-mediated pathology associated with COVID-19. A recombinant fragment of human (rfh)SP-D has recently been shown to neutralize SARS-CoV-2. Further work investigating the potential therapeutic role of SP-A and SP-D in COVID-19 and other infectious and inflammatory diseases is indicated.

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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

Cited by 4 publications

References 33 publications

The Role of Pulmonary Surfactants in the Treatment of Acute Respiratory Distress Syndrome in COVID-19

The Role of Pulmonary Surfactants in the Treatment of Acute Respiratory Distress Syndrome in COVID-19

Inhalations with surfactant-BL in the late respiratory phase of COVID-19 in the patient with a severe course of the disease

SP-A and SP-D: Dual Functioning Immune Molecules With Antiviral and Immunomodulatory Properties

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