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2.
J Clin Immunol ; 41(7): 1607-1620, 2021 10.
Article in English | MEDLINE | ID: covidwho-1298388

ABSTRACT

The complement system, a network of highly-regulated proteins, represents a vital part of the innate immune response. Over-activation of the complement system plays an important role in inflammation, tissue damage, and infectious disease severity. The prevalence of MERS-CoV in Saudi Arabia remains significant and cases are still being reported. The role of complement in Middle East Respiratory Syndrome coronavirus (MERS-CoV) pathogenesis and complement-modulating treatment strategies has received limited attention, and studies involving MERS-CoV-infected patients have not been reported. This study offers the first insight into the pulmonary expression profile including seven complement proteins, complement regulatory factors, IL-8, and RANTES in MERS-CoV infected patients without underlying chronic medical conditions. Our results significantly indicate high expression levels of complement anaphylatoxins (C3a and C5a), IL-8, and RANTES in the lungs of MERS-CoV-infected patients. The upregulation of lung complement anaphylatoxins, C5a, and C3a was positively correlated with IL-8, RANTES, and the fatality rate. Our results also showed upregulation of the positive regulatory complement factor P, suggesting positive regulation of the complement during MERS-CoV infection. High levels of lung C5a, C3a, factor P, IL-8, and RANTES may contribute to the immunopathology, disease severity, ARDS development, and a higher fatality rate in MERS-CoV-infected patients. These findings highlight the potential prognostic utility of C5a, C3a, IL-8, and RANTES as biomarkers for MERS-CoV disease severity and mortality. To further explore the prediction of functional partners (proteins) of highly expressed proteins (C5a, C3a, factor P, IL-8, and RANTES), the computational protein-protein interaction (PPI) network was constructed, and six proteins (hub nodes) were identified.


Subject(s)
Chemokine CCL5/genetics , Chemokine CCL5/metabolism , Complement C3a/metabolism , Complement C5a/metabolism , Coronavirus Infections/diagnosis , Interleukin-8/metabolism , Lung/metabolism , Middle East Respiratory Syndrome Coronavirus/physiology , Aged , Biomarkers/metabolism , Complement C3a/genetics , Complement C5a/genetics , Coronavirus Infections/metabolism , Coronavirus Infections/mortality , Female , Humans , Interleukin-8/genetics , Male , Middle Aged , Prognosis , Severity of Illness Index , Survival Analysis , Up-Regulation
3.
Pharmaceutics ; 13(4)2021 Apr 06.
Article in English | MEDLINE | ID: covidwho-1178386

ABSTRACT

Sialic acid that presents on the surface of lung epithelial cells is considered as one of the main binding targets for many respiratory viruses, including influenza and the current coronavirus (SARS-CoV-2) through the viral surface protein hemagglutinin. Gold nanoparticles (Au NPs) are extensively used in the diagnostic field owing to a phenomenon known as 'surface plasmonic resonance' in which the scattered light is absorbed by these NPs and can be detected via UV-Vis spectrophotometry. Consequently, sialic acid conjugated Au NPs (SA-Au NPs) were utilized for their plasmonic effect against SARS-CoV-2, influenza B virus, and Middle-East respiratory syndrome-related coronavirus (MERS) in patients' swab samples. The SA-Au NPs system was prepared by a one-pot synthesis method, through which the NPs solution color changed from pale yellow to dark red wine color, indicting its successful preparation. In addition, the SA-Au NPs had an average particle size of 30 ± 1 nm, negative zeta potential (-30 ± 0.3 mV), and a UV absorbance of 525 nm. These NPs have proven their ability to change the color of the NPs solutions and patients' swabs that contain SARS-CoV-2, influenza B, and MERS viruses, suggesting a rapid and straightforward detection tool that would reduce the spread of these viral infections and accelerate the therapeutic intervention.

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