A possible role for GRP78 in cross vaccination against COVID-19.
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ABSTRACT:
SUBMITTER: Elfiky AA
PROVIDER: S-EPMC7486427 | biostudies-literature | 2021 Feb
REPOSITORIES: biostudies-literature
Publications
A possible role for GRP78 in cross vaccination against COVID-19.
Elfiky Abdo A AA Ibrahim Ibrahim M IM Ismail Alaa M AM Elshemey Wael M WM
The Journal of infection 20200910 2
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Project description:Mucormycosis is a severe fungal infection reported in many cancer survivors, diabetic and immune-suppressed patients during organ transplants. A vast spark in the reported COVID-19 cases is noticed in India during the second wave in May 2021, when Mucormycosis is declared an epidemic. Despite being a rare disease, the mortality rate associated with Mucormycosis is more than 40%. Spore coat proteins (CotH) are essential proteins in many pathogenic bacteria and fungi. CotH3 was reported as the vital protein required for fungal virulence in Mucormycosis. We previously reported the involvement of the host cell-surface receptor GRP78 in SARS-CoV-2 spike recognition. Additionally, GRP78 is known to be the virulence factor during Mucormycosis. Using state-of-the-art structural bioinformatics and molecular modeling tools, we predicted the GRP78 binding site to the Rhizopus delemar CotH3 protein. Our findings pave the way toward rationally designing small molecule inhibitors targeting the GRP78 and its counter proteins in both pathogenic viral (SARS-CoV-2 spike) and fungal (R. delemar CotH3) diseases.
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Project description:Messenger RNA (mRNA) vaccines represent a new class of vaccines that has been shown to be highly effective during the COVID-19 pandemic and that holds great potential for other preventative and therapeutic applications. Understanding the underlying mechanisms of the immune responses induced by this novel vaccine type and their relation to vaccine responses might help to further refine and optimize future vaccine design. In this study, we conducted an in-depth analysis of the blood transcriptome before and 24h after second and third vaccination with licensed mRNA vaccines against COVID-19 in humans, following a prime vaccination with either mRNA or ChAdOx vaccines. Utilizing an unsupervised weighted gene correlation network analysis, we identified distinct gene networks of co-varying genes characterized by either an expressional up- or down-regulation in response to vaccination. Down-regulated networks were associated with cell metabolic processes and regulation of transcription factors, while up-regulated networks were associated with myeloid differentiation, antigen presentation, and antiviral, interferon-driven pathways. Within this interferon-associated network, we identified highly connected hub genes such as STAT2 and RIGI, potentially playing important regulatory roles in the vaccine-induced immune response. The expression profile of this network significantly correlated with S1-specific IgG levels at the follow-up visit in vaccinated individuals. Those findings could be corroborated in an independent cohort of mRNA vaccine recipients. Collectively, insights from this study might contribute to current research endeavors aimed at further enhancing/ or optimizing vaccine-induced immunity.
2024-01-29 | GSE247401 | GEO
Project description:BackgroundFrequent mutations of the COVID-19 virus, such as the Delta and Omicron variants, have prolonged the pandemic. Rich countries have approved the booster shots (3rd doses) of vaccine, but this causes further delay of vaccination in developing countries. This raises the risk of further mutations, which may lower the efficacy of currently available vaccines. As herd immunity by universal vaccination is essential to end the pandemic, the COVID-19 Vaccine Global Access (COVAX) facility has been established to provide developing countries with subsidized vaccines. However, a critical issue is that the developing countries also need to effectively deploy vaccines to citizens. Although this argument suggests positive effects of good national governance on vaccination coverage, to the best of our knowledge, there is no cross-country evidence on the role of national governance in increasing the coverage of COVID-19 vaccines among citizens. The goal of this study was to examine the association between the national governance and vaccination coverage among developing countries.MethodsUsing cross-country data, an ordinary least squares regression was conducted to examine the association between the national governance index and three outcomes: (1) the number of days until the administration of the first dose in the country since December 2019, (2) the number of doses per 100 citizens as of the end of July 2021, and (3) the selection of approved vaccine manufacturers. The results were compared between the model including all countries and the model excluding the member countries of Organisation for Economic Co-operation and Development (OECD).ResultsA one standard deviation increase in the national governance index was associated with 9.1 days (95%CI: -15.76, -2.43) earlier administration of vaccines in the country, and a 12.1 dose increase (95%CI: 4.76, 19.34) per 100 citizens. These associations were larger in the non-OECD sample. The results also indicated the role of governance in the selection of the administered vaccines.ConclusionThe provision of subsidized vaccines alone is not sufficient to control the spread of infection in developing countries; logistical and administrative support should also be offered, especially in countries with poor governance.Trial registrationNot applicable.
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Project description:BackgroundThis study aims to assess the uptake of maternal pertussis and COVID-19 vaccination and the intention towards accepting the maternal influenza vaccination. Insights into different socio-demographic factors related to maternal vaccination coverage might help to address vaccine acceptance and improve maternal vaccine uptake in the future.MethodsWe conducted a cross-sectional survey among pregnant women and recent mothers, up to 6 months post-partum. The primary outcome measures of this study were behaviour for maternal pertussis and COVID-19 vaccination, and maternal influenza vaccination intention. Associations between socio-demographic factors and maternal pertussis vaccination and maternal COVID-19 vaccination behaviour; and socio-demographic factors and maternal influenza vaccination intention were assessed using binary logistic regression analyses.ResultsIn total 1361 respondents filled out the questionnaire. Almost all women (95%) were vaccinated against pertussis during pregnancy, while almost two-third were vaccinated against COVID-19 during pregnancy (58%) and almost one-third (28%) had a positive intention towards receiving the maternal influenza vaccination. Results show that young maternal age and low education level were associated with lower maternal vaccination acceptance.ConclusionVaccination campaigns focusing on the severity of diseases that are prevented, are needed to increase maternal vaccine acceptance in younger and low-educated pregnant women. We expect that differences in vaccination coverage between the three maternal vaccinations might partly be explained by existing recommendations, campaigns and whether the vaccination is part of the national immunisation program.
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Project description:Bacillus Calmette-Guérin (BCG) vaccine is currently used to prevent tuberculosis infection. The vaccine was found to enhance resistance to certain types of infection including positive sense RNA viruses. The current COVID-19 pandemic is caused by positive sense RNA, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A higher mortality rate of COVID-19 patients was reported in countries where BCG vaccination is not routinely administered, when compared to the vaccinated ones. We hypothesized that BCG vaccine may control SARS-CoV2 infection via modulating the monocyte immune response. We analyzed GSE104149 dataset to investigate whether human monocytes of BCG-vaccinated individuals acquire resistance to SARS-CoV-2 infection. Differentially expressed genes obtained from the dataset were used to determine enriched pathways, biological processes, and molecular functions for monocytes post BCG vaccination. Our data show that BCG vaccine promotes a more effective immune response of monocytes against SARS-CoV2, but probably not sufficient to prevent the infection.
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Project description:The outbreak of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has led to coronavirus disease-19 (COVID-19); a pandemic disease that has resulted in devastating social, economic, morbidity and mortality burdens. SARS-CoV-2 infects cells following receptor-mediated endocytosis and priming by cellular proteases. Following uptake, SARS-CoV-2 replicates in autophagosome-like structures in the cytosol following its escape from endolysosomes. Accordingly, the greater endolysosome pathway including autophagosomes and the mTOR sensor may be targets for therapeutic interventions against SARS-CoV-2 infection and COVID-19 pathogenesis. Naturally existing compounds (phytochemicals) through their actions on endolysosomes and mTOR signaling pathways might provide therapeutic relief against COVID-19. Here, we discuss evidence that some natural compounds through actions on the greater endolysosome system can inhibit SARS-CoV-2 infectivity and thereby might be repurposed for use against COVID-19.
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Project description:The COVID-19 pandemic in Egypt is a part of the worldwide global crisis of coronavirus 2 (SARS-CoV-2). The contagious life-threatening condition causes acute respiratory syndrome. The present study aimed to assess the compounds identified by LC-MS of the methanolic leaves extracts from three conifers trees cultivated in Egypt (Araucaria bidwillii, Araucaria. cunninghamii and Araucaria heterophylla) via docking technique as potential inhibitor of COVID-19 virus on multiple targets; viral main protease (Mpro, 6LU7), non-structural protein-16 which is a methyl transferase (nsp16, 6W4H) and RNA dependent RNA polymerase (nsp12, 7BV2). Among the three targets, nsp16 was the best target recognized by the tested compounds as can be deduced from docking studies. Moreover, the methanolic extract of A. cunninghamii showed the highest radical-scavenging activity using (DPPH test) with 53.7 µg/mL comparable to ascorbic acid with IC50 = 46 µg/mL The anti-inflammatory potential carried using enzyme linked immunoassay showed the highest activity for A. cunninghamii and A. bidwillii followed by A. heterophylla with IC50 = 23.20 ± 1.17 µg/mL, 82.83 ± 3.21 µg/mL and 221.13 ± 6.7 µg/mL, respectively (Celecoxib was used as a standard drug with IC50 = 141.92 ± 4.52 µg/mL). Moreover, a molecular docking study was carried for the LC-MS annotated metabolites to validate their anti-inflammatory inhibitory effect using Celecoxib as a reference compound and showed a high docking score (-7.7 kcal/mol) for Octadecyl (E) P-coumarate and (-7.3 kcal/mol) for secoisolariciresinol rhamnoside.Communicated by Ramaswamy H. Sarma.
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