scholarly journals SARS-CoV-2 inactivation by human defensin HNP1 and retrocyclin RC-101

2021 ◽  
Author(s):  
Elena Kudryashova ◽  
Ashley Zani ◽  
Geraldine Vilmen ◽  
Amit Sharma ◽  
Wuyuan Lu ◽  
...  

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 is an enveloped virus responsible for the COVID-19 respiratory disease pandemic. While induction of adaptive antiviral immunity via vaccination holds promise for combatting the pandemic, the emergence of new potentially more transmissible and vaccine-resistant variants of SARS-CoV-2 is an ever-present threat. Thus, it remains essential to better understand innate immune mechanisms that are active against the virus. One component of the innate immune system with broad anti-pathogen, including antiviral, activity is a group of cationic immune peptides termed defensins. The defensins' ability to neutralize enveloped and non-enveloped viruses and to inactivate numerous bacterial toxins correlate with their ability to promote the unfolding of thermodynamically pliable proteins. Accordingly, we found that human neutrophil α-defensin HNP1 and retrocyclin RC-101 destabilize SARS-CoV-2 Spike protein and interfere with Spike-mediated membrane fusion and SARS-CoV-2 infection in cell culture. We show that HNP1 binds to Spike with submicromolar affinity. Although binding of HNP1 to serum albumin is more than 20-fold weaker, serum reduces the anti-SARS-CoV-2 activity of HNP1. At high concentrations of HNP1, its ability to inactivate the virus was preserved even in the presence of serum. These results suggest that specific α- and θ-defensins may be valuable tools in developing SARS-CoV-2 infection prevention strategies.

2017 ◽  
Vol 4 (1) ◽  
pp. 33-37
Author(s):  
L.L. Vorontsova ◽  
V.A. Kovalenko ◽  
M.I. Dub ◽  
M.Ye. Zhuravlova

EFFECT OF ENDOTOXIN AGGRESSION ON DEVELOPMENT OF IMMUNE HOMEOSTASIS DAMAGES IN INFERTILE MENVorontsova L.L., Kovalenko V.A., Dub M.I., Zhuravlova M.Ye.The article describes that studying condition of endotoxin-antiendotoxin system it has been revealed that endotoxin aggression occurs in infertile men it transforms acute character (in considerable decreasing ejaculate fertility) into chronic one (in absolute lack of fertile properties in ejaculate). Changes for indices of immune system link damaged indicate increasing tension, that, obviously, assumes alternative available agents (in particular, gram-negative bacteria), which further damages of spermatogenesis. It is possible to assume, that endotoxin aggression, in particular, chronic one is an important link for pathogenesis of male infertility, thought high concentrations in LPS potentiate immune phagocytic link, obviously, as compensator.Keywords: endotoxin, innate immune system, male infertility. РОЛЬ ЕНДОТОКСИНОВОЇ АГРЕСІЇ У РОЗВИТКУ ПОРУШЕНЬ ІМУННОГО ГОМЕОСТАЗУ У БЕЗПЛІДНИХ ЧОЛОВІКІВВоронцова Л.Л., Коваленко В.А., Дуб М.І., Журавльова М.Є.В результаті проведеного дослідження стану ендотоксин-антиендотоксинової системи виявлено, що у чоловіків з безпліддям має місце ендотоксинові агресія, яка змінює гострий характер (при значному зниженні фертильності еякуляту) на хронічний (при повній відсутності фертильних властивостей еякуляту). Зміни показників вродженої ланки імунної системи, що спостерігаються у безплідних чоловіків свідчать про зростання напруги, що, вочевидь, вказує на наявність альтернативних факторів (зокрема, грамнегативних бактерій), які сприяють, в свою чергу, порушенню сперматогенезу. Таким чином, ендотоксинова агресія, і зокрема хронічна, є важливою ланкою патогенезу чоловічого безпліддя, в той час як висока концентрація ЛПС сприяє активації фагоцитарної ланки імунної системи, вочевидь, компенсаторного характеру.Ключові слова: вроджений імунітет, ендотоксин, чоловіче безпліддя. РОЛЬ ЭНДОТОКСИНОВОЙ АГРЕССИИ В РАЗВИТИИ НАРУШЕНИЙ ИММУННОГО ГОМЕОСТАЗА У БЕСПЛОДНЫХ МУЖЧИН Воронцова Л.Л., Коваленко В.А., Дуб М.И., Журавлева М.Е.В результате проведенного исследования состояния энотоксин-антиэндотоксиновой системы выявлено, что у мужчин с бесплодием имеет место эндотоксиновая агрессия, которая изменяет острый характер (при значительном снижении фертильности эякулята) на хронический (при полном отсутствии фертильных свойств эякулята). Изменения показателей врожденного звена иммунной системы, наблюдающиеся у бесплодных мужчин, свидетельствуют об усилении напряжения, и, по-видимому, указывают на наличие альтернативных факторов (в частности, грамотрицательных бактерий), которые способствуют, в свою очередь, нарушению сперматогенеза. Таким образом, эндотоксиновая агрессия, и в частности хроническая, является важным звеном патогенеза мужского бесплодия, в то время как высокая концентрация ЛПС способствует активации фагоцитарного звена иммунной системы, по-видимому, компенсаторного характера.Ключевые слова: врожденный иммунитет, мужское бесплодие, эндотоксин.


Author(s):  
Mads Delbo Larsen ◽  
Erik L. de Graaf ◽  
Myrthe E. Sonneveld ◽  
H. Rosina Plomp ◽  
Federica Linty ◽  
...  

AbstractIgG antibodies are crucial for protection against invading pathogens. A highly conserved N-linked glycan within the IgG-Fc-tail, essential for IgG function, shows variable composition in humans. Afucosylated IgG variants are already used in anti-cancer therapeutic antibodies for their elevated binding and killing activity through Fc receptors (FcγRIIIa). Here, we report that afucosylated IgG which are of minor abundance in humans (∼6% of total IgG) are specifically formed against surface epitopes of enveloped viruses after natural infections or immunization with attenuated viruses, while protein subunit immunization does not elicit this low fucose response. This can give beneficial strong responses, but can also go awry, resulting in a cytokine-storm and immune-mediated pathologies. In the case of COVID-19, the critically ill show aggravated afucosylated-IgG responses against the viral spike protein. In contrast, those clearing the infection unaided show higher fucosylation levels of the anti-spike protein IgG. Our findings indicate antibody glycosylation as a potential factor in inflammation and protection in enveloped virus infections including COVID-19.


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 796
Author(s):  
Koji Kitazawa ◽  
Stefanie Deinhardt-Emmer ◽  
Takenori Inomata ◽  
Sharvari Deshpande ◽  
Chie Sotozono

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health problem. Although the respiratory system is the main impaired organ, conjunctivitis is one of its common findings. However, it is not yet understood if SARS-CoV-2 can infect the eye and if the ocular surface can be a potential route of SARS-CoV-2 transmissions. Our review focuses on the viral entry mechanisms to give a better understanding of the interaction between SARS-CoV-2 and the eye. We highlighted findings that give evidence for multiple potential receptors of SARS-CoV-2 on the ocular surface. Additionally, we focused on data concerning the detection of viral RNA and its spike protein in the various ocular tissues from patients. However, the expression level seemed to be relatively low compared to the respiratory tissues as a result of a unique environment surrounding the ocular surface and the innate immune response of SARS-CoV-2. Nevertheless, our review suggests the ocular surface as a potential route for SARS-CoV-2 transmission, and as a result of this study we strongly recommend the protection of the eyes for ophthalmologists and patients at risk.


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