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    IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection MESHD

    Authors: Bruce A. Rosa; Mushtaq Ahmed; Dhiraj K. Singh; Jose Alberto Choreno-Parra; Journey Cole; Luis Armando Jimenez-Alvarez; Tatiana Sofia Rodriguez-Reyna; Bindu Singh; Olga Golzalez; Ricardo Carrion; Larry S. Schlesinger; John Martin; Joaquin Zuniga; Makedonka Mitreva; Shabaana A Khader; Deepak Kaushal

    doi:10.1101/2020.08.06.239798 Date: 2020-08-06 Source: bioRxiv

    The novel virus SARS-CoV-2 has infected more than 14 million people worldwide resulting in the Coronavirus disease MESHD 2019 (COVID-19). Limited information on the underlying immune mechanisms that drive disease MESHD or protection during COVID-19 severely hamper development of therapeutics and vaccines. Thus, the establishment of relevant animal models that mimic the pathobiology of the disease is urgent. Rhesus macaques infected with SARS-CoV-2 exhibit disease pathobiology similar to human COVID-19, thus serving as a relevant animal model. In the current study, we have characterized the transcriptional signatures induced in the lungs of juvenile and old rhesus macaques following SARS-CoV-2 infection MESHD. We show that genes associated with Interferon (IFN) signaling, neutrophil degranulation and innate immune pathways are significantly induced in macaque infected lungs MESHD, while pathways associated with collagen formation are downregulated. In COVID-19, increasing age TRANS is a significant risk factor for poor prognosis and increased mortality. We demonstrate that Type I IFN and Notch signaling pathways are significantly upregulated in lungs of juvenile infected MESHD macaques when compared with old infected macaques. These results are corroborated with increased peripheral neutrophil counts and neutrophil lymphocyte ratio in older individuals with COVID-19 disease. In contrast, pathways involving VEGF are downregulated in lungs of old infected macaques. Using samples from humans with SARS-CoV-2 infection MESHD and COVID-19, we validate a subset of our findings. Finally, neutrophil degranulation, innate immune system and IFN gamma signaling pathways are upregulated in both tuberculosis MESHD and COVID-19, two pulmonary diseases MESHD where neutrophils are associated with increased severity. Together, our transcriptomic studies have delineated disease pathways to improve our understanding of the immunopathogenesis of COVID-19 to facilitate the design of new therapeutics for COVID-19.

    Mapping Systemic Inflammation MESHD and Antibody SERO Responses in Multisystem Inflammatory Syndrome MESHD in Children TRANS (MIS-C)

    Authors: Conor Gruber; Roosheel Patel; Rebecca Trachman; Lauren Lepow; Fatima Amanat; Florian Krammer; Karen M. Wilson; Kenan Onel; Daniel Geanon; Kevin Tuballes; Manishkumar Patel; Konstantinos Mouskas; Nicole Simons; Vanessa Barcessat; Diane Del Valle; Samantha Udondem; Gurpawan Kang; Sandeep Gangadharan; George Ofori-Amanfo; Adeeb Rahman; Seunghee Kim-Schulze; Alexander Charney; Sacha Gnjatic; Bruce Gelb; Miriam Merad; Dusan Bogunovic

    doi:10.1101/2020.07.04.20142752 Date: 2020-07-06 Source: medRxiv

    Initially, the global outbreak of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) spared children TRANS from severe disease. However, after the initial wave of infections, clusters of a novel hyperinflammatory disease MESHD have been reported in regions with ongoing SARS-CoV-2 MESHD epidemics. While the characteristic clinical features are becoming clear, the pathophysiology remains unknown. Herein, we report on the immune profiles of eight Multisystem Inflammatory Syndrome MESHD in Children TRANS (MIS-C) cases. We document that all MIS-C patients had evidence of prior SARS-CoV-2 exposure, mounting an antibody SERO response with normal isotype-switching and neutralization capability. We further profiled the secreted immune response by high-dimensional cytokine assays, which identified elevated signatures of inflammation MESHD (IL-18 and IL-6), lymphocytic and myeloid chemotaxis and activation (CCL3, CCL4, and CDCP1) and mucosal immune dysregulation HP (IL-17A, CCL20, CCL28). Mass cytometry immunophenotyping of peripheral blood SERO revealed reductions of mDC1 and non-classical monocytes, as well as both NK- and T- lymphocytes, suggesting extravasation to affected tissues. Markers of activated myeloid function were also evident, including upregulation of ICAM1 and FcR1 in neutrophil and non-classical monocytes, well-documented markers in autoinflammation MESHD and autoimmunity HP that indicate enhanced antigen presentation and Fc-mediated responses. Finally, to assess the role for autoimmunity HP secondary to infection, we profiled the auto-antigen reactivity of MIS-C plasma SERO, which revealed both known disease-associated autoantibodies (anti-La) and novel candidates that recognize endothelial, gastrointestinal and immune-cell antigens. All patients were treated with anti- IL6R antibody SERO or IVIG, which led to rapid disease resolution tracking with normalization of inflammatory markers.

    In silico multi-epitope vaccine against covid19 showing effective interaction with HLA-B*15:03

    Authors: Muniba Faiza; Tariq Abdullah; Jose Franklin Calderon-Tantalean; Manish Ravindranath Upadhyay; Abdelrahman H. Abdelmoneim; Fareeha Akram; Bhupender Singh Thakur; Ibrahim Abdulaziz; Chimaobi James Ononamadu; Dina Abdelazim Ghoraba; Saba Munawar; MD Fakhrul Islam Faruque; Collins Kigen; Abhishek Sharma; Ashwani Kumar; Aqsa Khalid; Ali Gharip; Ankit Gupta; Manne Manikumar; Uma Chaudhary

    doi:10.1101/2020.06.10.143545 Date: 2020-06-14 Source: bioRxiv

    The recent outbreak of severe acute respiratory syndrome MESHD (SARS) coronavirus (CoV)-2 (SARS-CoV-2) causing coronavirus disease MESHD (covid19) has posed a great threat to human health. Previous outbreaks of SARS-CoV MESHD and Middle East respiratory Syndrome CoV MESHD (MERS-CoV) from the same CoV family had posed similar threat to human health and economic growth. To date, not even a single drug specific to any of these CoVs has been developed nor any anti-viral vaccine is available for the treatment of diseases MESHD caused by CoVs. Subunits present in spike glycoproteins of SARS-CoV MESHD and SARS-CoV-2 are involved in binding to human ACE2 Receptor which is the primary method of viral invasion. As it has been observed in the previous studies that there are very minor differences in the spike glycoproteins of SARS-CoV MESHD and SARS-CoV-2. SARS-CoV-2 has an additional furin cleavage site that makes it different from SARS-CoV MESHD (Walls et al., 2020). In this study, we have analyzed spike glycoproteins of SARS-CoV-2 and SARS-CoV MESHD phylogenetically and subjected them to selection pressure analysis. Selection pressure analysis has revealed some important sites in SARS-CoV-2 and SARS-CoV spike glycoproteins MESHD that might be involved in their pathogenicity. Further, we have developed a potential multi-epitope vaccine candidate against SARS-CoV-2 by analyzing its interactions with HLA-B*15:03 subtype. This vaccine consists of multiple T-helper (TH) cells, B-cells, and Cytotoxic T-cells (CTL) epitopes joined by linkers and an adjuvant to increase its immunogenicity. Conservation of selected epitopes in SARS, MERS, and human hosts, suggests that the designed vaccine could provide cross-protection. The vaccine is designed in silico by following a reverse vaccinology method acknowledging its antigenicity, immunogenicity, toxicity MESHD, and allergenicity. The vaccine candidate that we have designed as a result of this work shows promising result indicating its potential capability of simulating an immune response.

    Global research trend in the treatment of the new Coronavirus diseases (COVID-19) : bibliometric analysis.

    Authors: Maxime Descartes Mbogning Fonkou; Abdourahamane YACOUBA

    doi:10.1101/2020.06.13.20122762 Date: 2020-06-14 Source: medRxiv

    The Coronavirus 2019 (COVID-19) pandemic has caused worldwide concern and has become a major medical problem. Vaccines and therapeutics are important interventions for the management of this outbreak. This study aims to used bibliometric methods to identify research trends in the domain of therapeutics and vaccines to cure patients with COVID-19 since the beginning of the pandemic. The Web of Science Core Collection database was retrieved for articles on therapeutic approaches to coronavirus disease MESHD management published between January 1, 2020 and May 20, 2020. Identified and analyzed the data included title, corresponding author, language, publication time, publication type, research focus. A total of 1569 articles on coronavirus therapeutic means from 84 countries were published in 620 journals. We note the remarkable progressive increase in the number of publications related to research on therapies and vaccines for COVID-19. The United States provided the largest number of articles (405), followed by China (364). Journal of Medical Virology published most of them (n=40). 1005 (64.05%) were articles, 286 (18.23%) were letters, 230 (14.66%) were reviews. The terms "COVID- 19" or " SARS-CoV-2" MESHD or "Coronavirus" or "hydroxychloroquine" or "chloroquine" or "2019-nCOV" or "ACE2" or "treatment" or "remdesivir" or " pneumonia HP pneumonia MESHD" were most frequently used, as shown in the density visualization map. A network analysis based on keyword co-occurrence revealed five distinct types of studies: clinical, biological, epidemiological, pandemic management, and therapeutics (vaccines and treatments). COVID-19 is a major disease that has had an impact on international public health at the global level. Several avenues for treatment and vaccines have been explored. Most of them focus on older drugs used to treat other diseases MESHD that have been effective for other types of coronaviruses. There is a discrepancy in the results obtained from the studies of the drugs included in this study. Randomized clinical trials are needed to evaluate older drugs and develop new treatment options.

    Ontological and Bioinformatic Analysis of Anti-Coronavirus Drugs and Their Implication for Drug Repurposing against COVID-19

    Authors: Yingtong Liu; Wallace K.B. Chan; Zhigang Wang; Junguk Hur; Jiangan Xie; Hong Yu; Yongqun He

    id:10.20944/preprints202003.0413.v1 Date: 2020-03-29 Source: Preprints.org

    Coronavirus-infected diseases MESHD have posed great threats to human health. In past years, highly infectious coronavirus-induced diseases MESHD, including COVID-19, SARS, and MERS, have resulted in world-wide severe infections HP. Our literature annotations identified 110 chemical drugs and 26 antibodies SERO effective against at least one human coronavirus infection MESHD in vitro or in vivo. Many of these drugs inhibit viral entry to cells and viral replication inside cells or modulate host immune responses. Many antimicrobial drugs, including antimalarial (e.g., chloroquine and mefloquine) and antifungal (e.g., terconazole and rapamycin) drugs as well as antibiotics (e.g., teicoplanin and azithromycin) were associated with anti-coronavirus activity. A few drugs, including remdesivir, chloroquine, favipiravir, and tocilizumab, have already been reported to be effective against SARS-CoV-2 infection MESHD in vitro or in vivo. After mapping our identified drugs to three ontologies ChEBI, NDF-RT, and DrON, many features such as roles and mechanisms of action (MoAs) of these drugs were identified and categorized. For example, out of 57 drugs with MoA annotations in NDF-RT, 47 have MoAs of different types of inhibitors and antagonists. A total of 29 anticoronaviral drugs are anticancer drugs with the antineoplastic role. Two clustering analyses, one based on ChEBI-based semantic similarity, the other based on drug chemical similarity, were performed to cluster 110 drugs to new categories. Moreover, differences in physicochemical properties among the drugs were found between those inhibiting viral entry and viral replication. A total of 163 host genes were identified as the known targets of 68 anti-coronavirus drugs, resulting in a network of 428 interactions among these drugs and targets. Chlorpromazine, dasatinib, and anisomycin are the hubs of the drug-target network with the highest number of connected target proteins. Many enriched pathways such as calcium signaling and neuroactive ligand-receptor interaction pathways were identified. These findings may be used to facilitate drug repurposing against COVID-19.

    Evaluating the Traditional Chinese Medicine (TCM) Officially Recommended in China for COVID-19 Using Ontology-Based Side-Effect Prediction Framework (OSPF) and Deep Learning

    Authors: Zeheng Wang; Liang Li; Jing Yan; Yuanzhe Yao

    id:10.20944/preprints202002.0230.v1 Date: 2020-02-17 Source: Preprints.org

    Ethnopharmacological relevance: Novel coronavirus disease MESHD (COVID-19) outbroke in Wuhan has imposed a huge influence onto the society in term of the public heath and economy. However, so far, no effective drugs or vaccines have been developed. Whereas, the Traditional Chinese Medicine (TCM) has been considered as a promising supplementary treatment for the disease owing to its clinically proven performance SERO on many diseases MESHD even like severe acute respiratory syndrome MESHD (SARS). Meanwhile, many side-effect ( SE MESHD) reports suggest the SE MESHD of the TCM prescriptions cannot be ignored in curing the COVID-19, especially because COVID-19 always simultaneously leads to dramatic degradation of the patients’ physical condition. How to evaluate the TCM regarding to their latent SE MESHD is a urgent challenge. Aim of the study: In this study, we use an ontology-based side-effect prediction framework (OSPF) developed in our previous work and Artificial Neural Network (ANN)-based deep learning to evaluate the TCM prescriptions that are officially recommended in China for novel coronavirus (COVID-19). Materials and methods: Firstly, we adopted the OSPF developed in our previous work, where an ontology-based model separate all the ingredients in a TCM prescription into two categories: hot and cold. Then, we established a database by converting each TCM prescription into a vector containing the ingredient dosage and the according hot/cold attribution as well as the safe/unsafe label. And, we trained the ANN model using this database, after which a safety indicator (SI), as the complementary percentage of side-effect ( SE MESHD) possibility, is then given for each TCM prescription. According to the proposed SI from high to low, we re-organize the recommended prescription list. Secondly, by using this method, we also evaluate the safety indicators of some other famous TCM prescriptions that are not in the recommended list but are used traditionally to cure flu-like diseases for extending the potential treatments. Results: Based on the SI generated in the ANN model, FTS, PMSP, and SF are the safest ones in recommended list, which all own a more-than-0.8 SI. Whereas, JHQG, LHQW, SFJD, XBJ, and SHL are the prescriptions that are most likely unsafe, where the indicators are all below 0.2. In the extra list, the indicators of XC, XQRS, CC, and CHBX are all above 0.8, and at the meantime, XZXS, SJ, QW, and KBD’s indicators are all below 0.2. Conclusions: In total, there are seven TCM prescriptions which own the indicators more than 0.8, suggesting these prescriptions should be considered firstly in curing COVID-19, if suitable. We believe this work will provide a reasonable suggestion for the society to choose proper TCM as the supplementary treatment for COVID-19. Besides, this work also introduces a pilot and enlightening method for creating a more reasonable recommendation list of TCM to other diseases.

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MeSH Disease
Human Phenotype

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