SARS-CoV-2 deregulates the vascular and immune functions of brain pericytes via spike protein

Spike-specific antibodies are central to effective COVID19 immunity. Research efforts have focused on antibodies that neutralize the ACE2-Spike interaction but not on non-neutralizing antibodies. Antibody-dependent phagocytosis is an immune mechanism enhanced by opsonization, where typically, more bound antibodies trigger a stronger phagocyte response. Here, we show that Spike-specific antibodies, dependent on concentration, can either enhance or reduce Spike-bead phagocytosis by monocytes independently of the antibody neutralization potential. Surprisingly, we find that both convalescent patient plasma and patient-derived monoclonal antibodies lead to maximum opsonization already at low levels of bound antibodies and is reduced as antibody binding to Spike protein increases. Moreover, we show that this Spike-dependent modulation of opsonization seems to affect the outcome in an experimental SARS-CoV-2 infection model. These results suggest that the levels of anti-Spike antibodies could influence monocyte-mediated immune functions and propose that non-neutralizing antibodies could confer protection to SARS-CoV-2 infection by mediating phagocytosis.

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Learned Placebo Effects in the Immune System

Zeitschrift für Psychologie ◽

10.1027/2151-2604/a000184 ◽

2014 ◽

Vol 222 (3) ◽

pp. 148-153 ◽

Cited By ~ 2

Author(s):

Sabine Vits ◽

Manfred Schedlowski

Keyword(s):

Nervous System ◽

Immune System ◽

Associative Learning ◽

Placebo Response ◽

Immunosuppressive Drug ◽

Immune Functions ◽

Placebo Effects ◽

New Therapeutic Approaches ◽

Biological Variables ◽

Experimental Approaches

Associative learning processes are one of the major neuropsychological mechanisms steering the placebo response in different physiological systems and end organ functions. Learned placebo effects on immune functions are based on the bidirectional communication between the central nervous system (CNS) and the peripheral immune system. Based on this “hardware,” experimental evidence in animals and humans showed that humoral and cellular immune functions can be affected by behavioral conditioning processes. We will first highlight and summarize data documenting the variety of experimental approaches conditioning protocols employed, affecting different immunological functions by associative learning. Taking a well-established paradigm employing a conditioned taste aversion model in rats with the immunosuppressive drug cyclosporine A (CsA) as an unconditioned stimulus (US) as an example, we will then summarize the efferent and afferent communication pathways as well as central processes activated during a learned immunosuppression. In addition, the potential clinical relevance of learned placebo effects on the outcome of immune-related diseases has been demonstrated in a number of different clinical conditions in rodents. More importantly, the learned immunosuppression is not restricted to experimental animals but can be also induced in humans. These data so far show that (i) behavioral conditioned immunosuppression is not limited to a single event but can be reproduced over time, (ii) immunosuppression cannot be induced by mere expectation, (iii) psychological and biological variables can be identified as predictors for this learned immunosuppression. Together with experimental approaches employing a placebo-controlled dose reduction these data provide a basis for new therapeutic approaches to the treatment of diseases where a suppression of immune functions is required via modulation of nervous system-immune system communication by learned placebo effects.

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First antibody against COVID-19 spike protein enters phase I

Nature Reviews Drug Discovery ◽

10.1038/d41573-020-00108-x ◽

2020 ◽

Vol 19 (7) ◽

pp. 435-435

Author(s):

Asher Mullard

Keyword(s):

Phase I ◽

Spike Protein

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Effect of thiolic-antioxidant ingestion on the relation between exploratory activity and immune functions in adult mice

Immunology Letters ◽

10.1016/s0165-2478(97)88754-8 ◽

1997 ◽

Vol 56 (1-3) ◽

pp. 470

Author(s):

M De la Fuente

Keyword(s):

Exploratory Activity ◽

Immune Functions ◽

Adult Mice

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Effects of combined acute versus chronic aerobic and resistance exercises on HbA1c, cardiovascular and immune functions in type 2 diabetic condition

Endocrine Abstracts ◽

10.1530/endoabs.43.oc3 ◽

2016 ◽

Author(s):

Sam Ibeneme ◽

Obed Azubuike ◽

Georgian Ibeneme ◽

Ifeoma Okoye ◽

Gerhard Fortwengel ◽

...

Keyword(s):

Immune Functions ◽

Resistance Exercises ◽

Type 2 Diabetic

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Novel Innate Immune Functions Revealed by Dynamic, Real-Time Live Imaging of Bacterial Infections

Critical Reviews™ in Immunology ◽

10.1615/critrevimmunol.v30.i2.10 ◽

2010 ◽

Vol 30 (2) ◽

pp. 107-117 ◽

Cited By ~ 4

Author(s):

Keira Melican ◽

Jorrit Boekel ◽

Monica Ryden-Aulin ◽

Agneta Richter-Dahlfors

Keyword(s):

Real Time ◽

Bacterial Infections ◽

Live Imaging ◽

Innate Immune ◽

Immune Functions

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Thermodynamics of the interaction between the spike protein of severe acute respiratory syndrome- coronavirus-2 and the receptor of human angiotensin converting enzyme 2. Effects of possible ligands

10.26434/chemrxiv.12186624.v3 ◽

2020 ◽

Author(s):

Cristina Garcia-Iriepa ◽

Cecilia Hognon ◽

Antonio Francés-Monerris ◽

Isabel Iriepa ◽

Tom Miclot ◽

...

Keyword(s):

Angiotensin Converting Enzyme ◽

Molecular Mechanisms ◽

Molecular Design ◽

Binding Free Energy ◽

Transmembrane Protein ◽

Spike Protein ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2 ◽

Rational Molecular Design ◽

Rational Evaluation

<div><p>Since the end of 2019, the coronavirus SARS-CoV-2 has caused more than 180,000 deaths all over the world, still lacking a medical treatment despite the concerns of the whole scientific community. Human Angiotensin-Converting Enzyme 2 (ACE2) was recently recognized as the transmembrane protein serving as SARS-CoV-2 entry point into cells, thus constituting the first biomolecular event leading to COVID-19 disease. Here, by means of a state-of-the-art computational approach, we propose a rational evaluation of the molecular mechanisms behind the formation of the complex and of the effects of possible ligands. Moreover, binding free energy between ACE2 and the active Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein is evaluated quantitatively, assessing the molecular mechanisms at the basis of the recognition and the ligand-induced decreased affinity. These results boost the knowledge on the molecular grounds of the SARS-CoV-2 infection and allow to suggest rationales useful for the subsequent rational molecular design to treat severe COVID-19 cases.</p></div>

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Sitagliptin: a potential drug for the treatment of SARS-CoV-2?

10.31222/osf.io/78mbt ◽

2020 ◽

Author(s):

Sanaa Bardaweel

Keyword(s):

Clinical Trials ◽

Drug Discovery ◽

Antimalarial Drug ◽

Drug Repurposing ◽

Spike Protein ◽

Diabetic Patients ◽

Potential Drug ◽

Chemokine Production ◽

Drug Discovery And Development ◽

Sequence Identity

Recently, an outbreak of fatal coronavirus, SARS-CoV-2, has emerged from China and is rapidly spreading worldwide. As the coronavirus pandemic rages, drug discovery and development become even more challenging. Drug repurposing of the antimalarial drug chloroquine and its hydroxylated form had demonstrated apparent effectiveness in the treatment of COVID-19 associated pneumonia in clinical trials. SARS-CoV-2 spike protein shares 31.9% sequence identity with the spike protein presents in the Middle East Respiratory Syndrome Corona Virus (MERS-CoV), which infects cells through the interaction of its spike protein with the DPP4 receptor found on macrophages. Sitagliptin, a DPP4 inhibitor, that is known for its antidiabetic, immunoregulatory, anti-inflammatory, and beneficial cardiometabolic effects has been shown to reverse macrophage responses in MERS-CoV infection and reduce CXCL10 chemokine production in AIDS patients. We suggest that Sitagliptin may be beneficial alternative for the treatment of COVID-19 disease especially in diabetic patients and patients with preexisting cardiovascular conditions who are already at higher risk of COVID-19 infection.

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