scholarly journals Structural assessment of SARS-CoV2 accessory protein ORF7a predicts LFA-1 and Mac-1 binding potential

2020 ◽  
Author(s):  
Zubair A Nizamudeen ◽  
Emma-Ruoqi Xu ◽  
Vivin Karthik ◽  
Mohamed Halawa ◽  
Kenton P Arkill ◽  
...  
Keyword(s):  
Binding Potential ◽  
Accessory Protein ◽  
Structural Homology ◽  
Human Immune System ◽  
Integrin Receptor ◽  
Structural Determinants ◽  
Docking Simulations ◽  
Mediated Effects ◽  
Integrin Binding Site ◽  
Human Immune

ORF7a is an accessory protein common to SARS-CoV1 and the recently discovered SARS-CoV2, which is causing the COVID19 pandemic. The ORF7a protein has a structural homology with ICAM-1 which binds to the T lymphocyte integrin receptor LFA-1. As COVID19 has a strong immune component as part of the disease, we sought to determine whether SARS-CoV2 would have a similar structural interaction with LFA-1. Using molecular docking simulations, we found that SARS-CoV2 ORF7a has the key structural determinants required to bind LFA-1 but also the related leukocyte integrin Mac-1, which is also known to be expressed by macrophages. Our study shows that SARS-CoV2 ORF7a protein has a conserved Ig immunoglobulin-like fold containing an integrin binding site that provides a mechanistic hypothesis for SARS-CoV2‘s interaction with the human immune system. This suggests that experimental investigation of ORF7a mediated effects on immune cells such as T lymphocytes and macrophages (leukocytes) could help understand the disease further and develop effective treatments.

Mother Culture, Meet Mother Nature

2018 ◽  
Author(s):  
Luc Faucher ◽  
Pierre Poirier
Keyword(s):  
Evolutionary Algorithms ◽  
Cultural Change ◽  
Evolutionary Information ◽  
Multiple Forms ◽  
Human Immune System ◽  
Units Of Selection ◽  
Pluralistic Approach ◽  
Human Immune ◽  
Plausible Theory ◽  
Different Time Scales

Research on the adaptive characteristics of the human immune system reveals that evolutionary algorithms are not strictly matters of replication. And research in genomics suggests that there is no a single source of evolutionary information that carries the same content in every environment. A plausible theory of cultural evolution must acknowledge the possibility that multiple selective algorithms are operating at different time-scales, on different units of selection, with different logical structures; but it must explain how different selective processes are interfaced to yield culturally stable phenomena. This paper advances an empirically plausible approach to memetics that recognizes a wider variety of evolutionary algorithms; and it advances a pluralistic approach to cultural change. Finally, it shows that multiple forms of processing, operating at different timescales, on different units of selection, collectively sustain the human capacity to form and use certain types of representations.

scholarly journals Metabolic Swifts Govern Normal and Malignant B Cell Lymphopoiesis

2021 ◽  
Vol 22 (15) ◽  
pp. 8269
Author(s):  
Aikaterini Poulaki ◽  
Stavroula Giannouli
Keyword(s):  
B Cell ◽  
B Lymphocytes ◽  
Control Program ◽  
Memory B Cells ◽  
Immunologic Memory ◽  
Human Immune System ◽  
B Cell Malignancies ◽  
Stringent Control ◽  
Human Immune ◽  
New Research

B lymphocytes are an indispensable part of the human immune system. They are the effective mediators of adaptive immunity and memory. To accomplish specificity against an antigen, and to establish the related immunologic memory, B cells differentiate through a complicated and strenuous training program that is characterized by multiple drastic genomic modifications. In order to avoid malignant transformation, these events are tightly regulated by multiple checkpoints, the vast majority of them involving bioenergetic alterations. Despite this stringent control program, B cell malignancies are amongst the top ten most common worldwide. In an effort to better understand malignant pathobiology, in this review, we summarize the metabolic swifts that govern normal B cell lymphopoiesis. We also review the existent knowledge regarding malignant metabolism as a means to unravel new research goals and/or therapeutic targets.

721 AT1412, a patient-derived CD9 antibody in preclinical development promoting tumor immune infiltration and inducing tumor rejection

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A763-A763
Author(s):  
Remko Schotte ◽  
Julien Villaudy ◽  
Martijn Kedde ◽  
Wouter Pos ◽  
Daniel Go ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Tumor Cells ◽  
Tumor Rejection ◽  
Human Immune System ◽  
Preclinical Development ◽  
High Affinity ◽  
Human Immune ◽  
A375 Melanoma

BackgroundAdaptive immunity to cancer cells forms a crucial part of cancer immunotherapy. Recently, the importance of tumor B-cell signatures were shown to correlate with melanoma survival. We investigated whether tumor-targeting antibodies could be isolated from a patient that cured (now 13 years tumor-free) metastatic melanoma following adoptive transfer of ex vivo expanded autologous T cells.MethodsPatient‘s peripheral blood B cells were isolated and tested for the presence of tumor-reactive B cells using AIMM’s immmortalisation technology. Antibody AT1412 was identified by virtue of its differential binding to melanoma cells as compared to healthy melanocytes. AT1412 binds the tetraspanin CD9, a broadly expressed protein involved in multiple cellular activities in cancer and induces ADCC and ADCP by effector cells.ResultsSpontaneous immune rejection of tumors was observed in human immune system (HIS) mouse models implanted with CD9 genetically-disrupted A375 melanoma (A375-CD9KO) tumor cells, while A375wt cells were not cleared. Most notably, no tumor rejection of A375-CD9KO tumors was observed in NSG mice, indicating that blockade of CD9 makes tumor cells susceptible to immune rejection.CD9 has been described to regulate integrin signaling, e.g. LFA-1, VLA-4, VCAM-1 and ICAM-1. AT1412 was shown to modulate CD9 function by enhancing adhesion and transmigration of T cells to endothelial (HUVEC) cells. AT1412 was most potently enhancing transendothelial T-cell migration, in contrast to a high affinity version of AT1412 or other high affinity anti-CD9 reference antibodies (e.g. ALB6). Enhanced immune cell infiltration is also observed in immunodeficient mice harbouring a human immune system (HIS). AT1412 strongly enhanced CD8 T-cell and macrophage infiltration resulting in tumor rejection (A375 melanoma). PD-1 checkpoint blockade is further sustaining this effect. In a second melanoma model carrying a PD-1 resistant and highly aggressive tumor (SK-MEL5) AT1412 together with nivolumab was inducing full tumor rejection, while either one of the antibodies alone did not.ConclusionsThe safety of AT1412 has been assessed in preclinical development and is well tolerated up to 10 mg/kg (highest dose tested) by non human primates. AT1412 demonstrated a half-life of 8.5 days, supporting 2–3 weekly administration in humans. Besides transient thrombocytopenia no other pathological deviations were observed. No effect on coagulation parameters, bruising or bleeding were observed macro- or microscopically. The thrombocytopenia is reversible, and its recovery accelerated in those animals developing anti-drug antibodies. First in Human clinical study is planned to start early 2021.Ethics ApprovalStudy protocols were approved by the Medical Ethical Committee of the Leiden University Medical Center (Leiden, Netherlands).ConsentBlood was obtained after written informed consent by the patient.

scholarly journals Transplacental priming of the human immune system with environmental allergens can occur early in gestation

2000 ◽  
Vol 106 (3) ◽  
pp. 530-536 ◽  
Author(s):  
Zsolt Szépfalusi ◽  
Josefa Pichler ◽  
Stefan Elsässer ◽  
Katalin van Duren ◽  
Christof Ebner ◽  
...  
Keyword(s):  
Immune System ◽  
Human Immune System ◽  
Human Immune

scholarly journals Antimicrobial peptides: The ancient arm of the human immune system

Virulence ◽  
2010 ◽  
Vol 1 (5) ◽  
pp. 440-464 ◽  
Author(s):  
Jochen Wiesner ◽  
Andreas Vilcinskas
Keyword(s):  
Immune System ◽  
Antimicrobial Peptides ◽  
Human Immune System ◽  
Human Immune

On the use of multiple heterogeneous devices to speedup the execution of a computational model of the Human Immune System

2015 ◽  
Vol 267 ◽  
pp. 304-313 ◽  
Author(s):  
T.M. do Nascimento ◽  
J.M. de Oliveira ◽  
M.P. Xavier ◽  
A.B. Pigozzo ◽  
R.W. dos Santos ◽  
...  
Keyword(s):  
Immune System ◽  
Computational Model ◽  
Human Immune System ◽  
Heterogeneous Devices ◽  
Human Immune

scholarly journals Binding of Androgen- and Estrogen-Like Flavonoids to Their Cognate (Non)Nuclear Receptors: A Comparison by Computational Prediction

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1613
Author(s):  
Giulia D’Arrigo ◽  
Eleonora Gianquinto ◽  
Giulia Rossetti ◽  
Gabriele Cruciani ◽  
Stefano Lorenzetti ◽  
...  
Keyword(s):  
Nuclear Receptors ◽  
Fruits And Vegetables ◽  
Computational Prediction ◽  
Membrane Receptors ◽  
Computational Docking ◽  
Docking Simulations ◽  
Mediated Effects ◽  
17Β Estradiol ◽  
G Protein Coupled ◽  
Relevant Degree

Flavonoids are plant bioactives that are recognized as hormone-like polyphenols because of their similarity to the endogenous sex steroids 17β-estradiol and testosterone, and to their estrogen- and androgen-like activity. Most efforts to verify flavonoid binding to nuclear receptors (NRs) and explain their action have been focused on ERα, while less attention has been paid to other nuclear and non-nuclear membrane androgen and estrogen receptors. Here, we investigate six flavonoids (apigenin, genistein, luteolin, naringenin, quercetin, and resveratrol) that are widely present in fruits and vegetables, and often used as replacement therapy in menopause. We performed comparative computational docking simulations to predict their capability of binding nuclear receptors ERα, ERβ, ERRβ, ERRγ, androgen receptor (AR), and its variant ART877A and membrane receptors for androgens, i.e., ZIP9, GPRC6A, OXER1, TRPM8, and estrogens, i.e., G Protein-Coupled Estrogen Receptor (GPER). In agreement with data reported in literature, our results suggest that these flavonoids show a relevant degree of complementarity with both estrogen and androgen NR binding sites, likely triggering genomic-mediated effects. It is noteworthy that reliable protein–ligand complexes and estimated interaction energies were also obtained for some suggested estrogen and androgen membrane receptors, indicating that flavonoids could also exert non-genomic actions. Further investigations are needed to clarify flavonoid multiple genomic and non-genomic effects. Caution in their administration could be necessary, until the safe assumption of these natural molecules that are largely present in food is assured.

New Perspectives for SARS-CoV-2 Rapid Detection

Coronaviruses ◽  
2021 ◽  
Vol 02 ◽  
Author(s):  
Latifa Khattabi ◽  
Mustapha Mounir Bouhenna ◽  
Feriel Sellam
Keyword(s):  
Rapid Detection ◽  
High Sensitivity ◽  
The Other ◽  
Host Cells ◽  
Rt Pcr ◽  
Human Immune System ◽  
Virus Attachment ◽  
Testing Procedures ◽  
Diagnostic Kits ◽  
Human Immune

: The present paper elucidates the conceivable application of two key molecules in SARS-CoV-2 detection of suspected infected persons. These molecules were selected from the basis of ACE-2 and S protein strong interaction that allows virus attachment to its host cells, on the other hand specific immunocompetant effectors generated by human immune system during the infection. Several testing procedures are already used to diagnose SARS-CoV-2 infection, particularly RT-PCR technique. ELISA and LFIA are possible assays for the employment of shACE-2/ hAc-anti-S (the molecules of interest) as the main agents of the test and confer a dual principal functions (capture and detection). The future diagnostic kits involving shACE-2 and hAc-anti-S will have the particularity of high sensitivity and rapid detection in addition to its advantage of relatively easy conception. It could be largely considered as a technical advanced kits in regards to the current SARS-CoV-2 diagnostic immunoassays.

Al-Muddaththir of the Quran Linked to the Covid-19 and Spanish Flu Pandemics: Circumstantial Evidence

2021 ◽  
Vol 02 (02) ◽  
Author(s):  
Baback Khodadoost ◽  
Keyword(s):  
Immune System ◽  
Circumstantial Evidence ◽  
The Moon ◽  
Human Immune System ◽  
Main Emphasis ◽  
Spanish Flu ◽  
Human Immune

Recently there have been speculations concerning a possible link between the covid-19 pandemic and al-Muddaththir, the 74th chapter of the Quran. An examination of this chapter presented in this article shows further evidences in support of these speculations. It is shown that indications of not only the current Covid-19 pandemic, but also the horrific 1918 Spanish flu can be detected in chapter 74. The main emphasis of this article will be to demonstrate the timings of the pandemic events as they appear to have been encoded in four of the chapter verses. The concept of Translational-Coding and in particular, its use in decoding one of the time-informing verses will be explained. A remarkable scheme of al-Muddaththir to announce the exact occurring years of the two major pandemics, will also be exposed. Coincidences of the Super Moon occurrences with major events of both, Covid-19 and Spanish flu pandemics, will be shown as the possible reason for “by the moon” swearing in verse 74:32. In connection with these observed coincidences, possible effect of the moon’s differential gravity on suppression of the human immune system during a Super Moon occurrence will be addressed. Some other verses in al-Muddaththir with possible relevance to the pandemic perspective of this chapter will also be discussed.

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