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.
【저자키워드】 SARS-CoV-2, Innate immunity, angiotensin converting enzyme 2, Spike protein, Surfactant protein D, human pulmonary collectins, 【초록키워드】 Treatment, coronavirus, SARS-CoV, SARS-COV-2 infection, Human, spike glycoprotein, animal models, in vitro, influenza A, viral entry, immune, hACE2, Receptor binding domain, serum, Surveillance, cells, HCoV-229E, Pathogens, respiratory, in vivo, inhibitor, epithelial, binding, innate immune, Interaction, Ex vivo, acute respiratory syndrome, enzyme, therapeutic potential, protective role, S1 protein, previous study, viral pathogen, SARS-CoV-2 S1, mucosal surface, highlight, reported, the patient, composed, inhibited, suggested, expressing, reduction in, 16HBE, CRD, HEK293T cell, overexpressing, pseudotyped lentiviral particle, RLU, 【제목키워드】 spike, Human, Particle, surfactant, bind, Act,