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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (654)

ProteinN (149)

NSP5 (75)

ComplexRdRp (46)

ProteinE (43)


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SARS-CoV-2 Proteins
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    COVID-19 MESHD vaccine impact on rates of SARS-CoV-2 cases and post vaccination strain sequences among healthcare workers at an urban academic medical center: a prospective cohort study

    Authors: Tara C Bouton; Sara Lodi; Jacquelyn Turcinovic; Sarah E Weber; Emily Quinn; Cathy Korn; Jacqueline Steiner; Elissa M Schechter-Perkins; Elizabeth Duffy; Elizabeth J. Ragan; Bradford P. Taylor; Beau Schaeffer; Nancy Miller; Ravin Davidoff; William P. Hanage; John Connor; Cassandra Pierre; Karen R Jacobson

    doi:10.1101/2021.03.30.21254655 Date: 2021-03-31 Source: medRxiv

    Background: COVID-19 MESHD vaccine trials and post-implementation data suggest vaccination decreases SARS-CoV-2 infections MESHD SARS-CoV-2 infection MESHDs. Objective: Estimate COVID-19 MESHD vaccinations impact on SARS-CoV-2 case rates and viral diversity among healthcare workers (HCW) during a high community prevalence period. Design, Setting, Participants: A prospective cohort study from Boston Medical Center (BMC)s HCW vaccination program, where staff received two doses of BNT162b2 or mRNA-1273. Measurements: PCR-confirmed SARS-CoV-2 cases among HCWs from December 09, 2020 to February 23, 2021. Weekly SARS-CoV-2 rates per 100,000 person-day overall and by time from first injection (1-14 and >14 days) were compared with surrounding community rates. Viral genome sequences from SARS CoV-2 positive samples. Results: SARS-CoV-2 cases occurred in 1.4% (96/7109) of HCWs given at least a first dose and 0.3% (17/5913) of HCWs given both vaccine doses. Adjusted SARS-CoV-2 infection MESHD rate ratios were 0.73 (95% CI 0.53-1.00) 1-14 days and 0.18 (0.10-0.32) >14 days from first dose. HCW SARS-CoV-2 cases >14 days from initial dose compared to within 14 days were more often older (46 versus 38 years, p=0.007), Latinx (10% versus 8%, p=0.03), and asymptomatic (48% versus 11%, p=0.0002). SARS-CoV-2 rates among HCWs fell below those of the surrounding community, with a 18% versus 11% weekly decrease respectively (p=0.14). Comparison of 48 SARS-CoV-2 genomes sequenced from post-first dose cases did not indicate selection pressure towards known spike-antibody escape mutations. Limitations: Unable to adjust for infection risk outside of the workplace. Lack follow up on symptoms post SARS-CoV-2 diagnosis. Small number of vaccinated HCW cases. Conclusion: Our results indicate a positive impact of COVID-19 MESHD vaccines on SARS-CoV-2 case rates. Post-vaccination isolates did not show unusual genetic diversity or selection for mutations of concern.

    Exploring the role of glycans in the interaction of SARS-CoV-2 RBD MESHD and human receptor ACE2

    Authors: Kien Nguyen; Srirupa Chakraborty; Rachael Mansbach; Bette Korber; S. Gnanakaran

    doi:10.1101/2021.03.30.437783 Date: 2021-03-31 Source: bioRxiv

    COVID-19 MESHD is a highly infectious respiratory disease MESHD caused by the novel coronavirus SARS-CoV-2. It has become a global pandemic and its frequent mutations may pose new challenges for vaccine design. During viral infection, the Spike RBD of SARS-CoV-2 binds the human host cell receptor ACE2 HGNC, enabling the virus to enter the host cell. Both the Spike and ACE2 HGNC are densely glycosylated, and it is unclear how distinctive glycan types may modulate the interaction of RBD and ACE2 HGNC. Detailed understanding of these determinants is key for the development of novel therapeutic strategies. To this end, we perform extensive all-atom simulations of the (i) RBD- ACE2 HGNC complex without glycans, (ii) RBD- ACE2 HGNC with oligomannose MAN9 HGNC glycans in ACE2 HGNC, and (iii) RBD- ACE2 HGNC with complex FA2 HGNC glycans in ACE2 HGNC. These simulations identify the key residues at the RBD- ACE2 HGNC interface that form contacts with higher probabilities, thus providing a quantitative evaluation that complements recent structural studies. Notably, we find that this RBD- ACE2 HGNC contact signature is not altered by the presence of different glycoforms, suggesting that RBD- ACE2 HGNC interaction is robust. Applying our simulated results, we illustrate how the recently prevalent N501Y mutation may alter specific interactions with host ACE2 HGNC that facilitate the virus-host binding. Furthermore, our simulations reveal how the glycan on Asn90 of ACE2 HGNC can play a distinct role in the binding and unbinding of RBD. Finally, an energetics analysis shows that MAN9 HGNC glycans on ACE2 HGNC decrease RBD- ACE2 HGNC affinity, while FA2 HGNC glycans lead to enhanced binding of the complex. Together, our results provide a more comprehensive picture of the detailed interplay between virus and human receptor, which is much needed for the discovery of effective treatments that aim at modulating the physical-chemical properties of this virus.

    Arrayed multicycle drug screens identify broadly acting chemical inhibitors for repurposing against SARS CoV 2

    Authors: Luca P Murer; Romain Volle; Vardan Andriasyan; Nicole Meili; Liliane Yang; Daniela Sequeira; Alfonso Gomez-Gonzalez; Anthony Petkidis; Dominik Olszewski; Michael Bauer; Maarit Suomalainen; Fabien Kuttler; Gerardo Turcatti; Urs F Greber

    doi:10.1101/2021.03.30.437771 Date: 2021-03-31 Source: bioRxiv

    Coronaviruses (CoVs) circulate in humans and animals, and expand their host range by zoonotic and anthroponotic transmissions. Endemic human CoVs, such as 229E and OC43 cause limited respiratory disease MESHD, and elicit short term anti-viral immunity favoring recurrent infections. Yet, severe acute respiratory syndrome MESHD (SARS)-CoV-2 spreads across the globe with unprecedented impact on societies and economics. The world lacks broadly effective and affordable anti-viral agents to fight the pandemic and reduce the death toll. Here, we developed an image-based multicycle replication assay for focus formation of -coronavirus hCoV-229E-eGFP infected cells for screening with a chemical library of 5440 compounds arrayed in 384 well format. The li-brary contained about 39% clinically used compounds, 26% in phase I, II or III clinical trials, and 34% in preclinical development. Hits were counter-selected against toxicity MESHD, and challenged with hCoV-OC43 and SARS-CoV-2 in tissue culture and human bronchial and nasal epithelial explant cultures from healthy donors. Fifty three compounds inhibited hCoV-229E-GFP, 39 of which at 50% effective concentrations (EC50) < 2M, and were at least 2-fold separated from toxicity MESHD. Thirty nine of the 53 compounds inhibited the replication of hCoV-OC43, while SARS-CoV-2 was inhibited by 11 compounds in at least two of four tested cell lines. Six of the 11 compounds are FDA-approved, one of which is used in mouth wash formulations, and five are systemic and orally available. Here, we demonstrate that methylene blue (MB) and myco-phenolic acid (MPA), two broadly available low cost compounds, strongly inhibited shedding of infectious SARS-CoV-2 at the apical side of the cultures, in either pre- or post-exposure regimens, with somewhat weaker effects on viral RNA release indicated by RT-qPCR measurements. Our study illustrates the power of full cycle screens in repurposing clinical compounds against SARS-CoV-2. Importantly, both MB and MPA reportedly act as immunosuppressants, making them interesting candidates to counteract the cytokine storms affecting COVID-19 MESHD patients.

    Linking Diabetes mellitus MESHD to SARS-CoV-2 infection MESHD through differential targeting of the microRNAs in the Pancreas tissue MESHD

    Authors: Bhavya; Ekta Pathak; Rajeev Mishra

    doi:10.1101/2021.03.31.437823 Date: 2021-03-31 Source: bioRxiv

    Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) severity and Diabetes mellitus MESHD affect each other bidirectionally. The plus-sense single-stranded RNA (+ssRNA) genome of the SARS-CoV-2 virus can be targeted and suppressed by the host cell's microRNAs (miRNAs). Using the differential gene expression analysis between the mock-infected and the SARS-CoV-2-infected pancreatic MESHD tissue, we report five Diabetes MESHD-associated genes that are upregulated due to SARS-CoV-2 infection MESHD in the hESC pancreas tissues. Ten miRNAs regulating these five genes can potentially target the SARS-CoV-2 genome. We hypothesize that the SARS-CoV-2 genome copies in the infected human pancreas cell compete with the host cell native genes in being regulated by the native miRNAs. It leads to the reduced miRNA-regulation and, thus, the upregulation of the Diabetes MESHD-associated native genes. Thus, the resultant new-onset or elevated Diabetic symptoms MESHD may worsen the condition of COVID-19 MESHD patients.

    Six-month pulmonary impairment MESHD after severe COVID-19 MESHD: a prospective, multicenter follow-up study

    Authors: Paola Faverio; Fabrizio Luppi; Paola Rebora; Sara Busnelli; Anna Stainer; Martina Catalano; Luca Parachini; Anna Monzani; Stefania Galimberti; Francesco Bini; Bruno Dino Bodini; Monia Betti; Federica De Giacomi; Paolo Scarpazza; Elisa Oggionni; Alessandro Scartabellati; Luca Bilucaglia; Paolo Ceruti; Denise Modina; Sergio Harari; Antonella Caminati; Maria Grazia Valsecchi; Giacomo Bellani; Giuseppe Foti; Alberto Pesci

    doi:10.1101/2021.03.29.21254151 Date: 2021-03-30 Source: medRxiv

    Background and objective. Long-term pulmonary sequelae following SARS-CoV-2 pneumonia MESHD are not yet confirmed, however preliminary observations suggests a possible relevant clinical, functional and radiological impairment. The aim of this study was to identify and characterise pulmonary sequelae caused by SARS-CoV-2 pneumonia MESHD at 6-month follow-up. Methods. In this multicenter, prospective, observational cohort study, patients hospitalised for SARS-CoV-2 pneumonia MESHD and without prior diagnosis of structural lung diseases MESHD were stratified by maximum ventilatory support (oxygen only, continuous positive airway pressure ( CPAP HGNC) and invasive mechanical ventilation (IMV)) and followed up at 6 months from discharge. Pulmonary function tests and diffusion capacity for carbon monoxide (DLCO), 6 minutes walking test, chest X-ray, physical exam and modified Medical Research Council (mMRC) dyspnoea MESHD score were collected. Results. Between March and June 2020, 312 patients were enrolled (83, 27% women; median [IQR] age 61.1 [53.4,69.3] years). The parameters that showed the highest rate of impairment were DLCO and chest-X-ray, in 46% and 25% of patients, respectively. However, only a minority of patients reported dyspnoea MESHD (31%), defined as mMRC [≥] 1, or showed a restrictive ventilatory defects (9%). In the logistic regression model, having asthma MESHD as comorbidity was associated with DLCO impairment at follow-up, while prophylactic heparin administration during hospitalisation appeared as a protective factor. Need for invasive ventilatory support during hospitalisation was associated with chest imaging abnormalities MESHD. Conclusion. DLCO and radiological assessment appear to be the most sensitive tools to monitor patients with COVID-19 MESHD during follow-up. Future studies with longer follow-up are warranted to better understand pulmonary sequelae.

    Analyzing the Global Impact of COVID-19 MESHD Vaccination Progress: A Result-oriented Storytelling Approach

    Authors: Samrat Kumar Dey; Dr. Md. Mahbubur Rahman; Dr. Umme Raihan Siddiqi; Arpita Howlader; Arifuzzaman Tushar

    doi:10.1101/2021.03.26.21254432 Date: 2021-03-29 Source: medRxiv

    The next big step in combating the coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic will be gaining widespread acceptance of a vaccination campaign for severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), but achieving high uptake need proper understandings. Many health professionals, researchers, statisticians, and programmers to track the viruses spread in different parts of the world have used various methods. However, the proliferation of vaccines produced by talented scientists around the world has sparked a strong desire to extract meaningful insights from available data. Until now, several vaccines against coronavirus disease ( COVID-19 MESHD) have been approved and are being distributed worldwide in various regions. This study aims to report the detailed data analysis and result-oriented storytelling of the COVID-19 MESHD vaccination program of different countries across the globe. To analyze the vaccination trend globally this research utilized two different open datasets provided by ourworldindata.org and worldometers.info. An exploratory data analysis ( EDA HGNC) with interactive data visualization using various python libraries was conducted, and the results are presented in this article to better understand the impact of ongoing vaccination programs around the world. Apart from the valuable insights gained from the data of various countries, this investigation also included a comparison of the number of confirmed and death cases before and after vaccination to determine the efficacy of each vaccine in each country. The results show that a large number of people are still undecided about whether or not to get a COVID-19 MESHD vaccine, despite the virus's continued devastating effects on communities. Overall, our findings contribute to ongoing research aimed at informing policy on how to persuade the unvaccinated to be vaccinated.

    Targeting the Microbiome With KB109 in Outpatients with Mild to Moderate COVID-19 MESHD Reduced Medically Attended Acute Care Visits and Improved Symptom Duration in Patients With Comorbidities

    Authors: John P Haran; Yan Zheng; Katharine Knobil; Norma Alonzo-Palma; Jonathan Lawrence; Mark Wingertzahn

    doi:10.1101/2021.03.26.21254422 Date: 2021-03-29 Source: medRxiv

    Introduction In 2020, the world experienced the beginning of the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), also known as the coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic. Mounting evidence indicates that the gut microbiome plays a role in host immune response to infections and, in turn, may have an impact on the disease trajectory of SARS-CoV2 infection MESHD. However, it remains to be established whether modulation of the microbiome can impact COVID-19 MESHD-related symptomatology and patient outcomes. Therefore, we conducted a study designed to modulate the microbiome evaluating the safety and physiologic effects of KB109 combined with self-supportive care (SSC) vs SSC alone in non-hospitalized patients with mild to moderate COVID-19 MESHD. KB109 is a novel synthetic glycan developed to increase the production of gut microbial metabolites that support immune system homeostasis through gut microbiome modulation. Our goal was to gain a better understanding of the safety of KB109, the natural course of COVID-19 MESHD symptomatology, and the possible role of the gut microbiome in patients with mild to moderate COVID-19 MESHD. Methods Adult patients who tested positive for COVID-19 MESHD were randomized 1:1 to receive KB109 combined with SSC or SSC alone for 14 days and were then followed for an additional 21 days (35 days in total). Patients self-assessed their COVID-19 MESHD-related symptoms (8 cardinal symptoms plus 5 additional symptoms) and self-reported comorbidities. The primary and secondary objectives were to evaluate the safety of KB109 plus SSC compared with that of SSC alone and to evaluate selected measures of health, respectively. Results Between July 2, 2020 and December 23, 2020, 350 patients were randomized to receive KB109 and SSC (n=174) or SSC alone (n=176). Overall, the most common comorbidities reported were hypertension MESHD (18.0% [63/350 patients]) followed by chronic lung disease MESHD (8.6% 30/350 patients). KB109 was well tolerated with most treatment-emergent adverse events being mild to moderate in severity. The administration of KB109 plus SSC reduced medically-attended visits (ie, hospitalization, emergency room visits, or urgent care visits) by 50.0% in the overall population and by 61.7% in patients with [≥]1 comorbidity; in patients aged [≥]45 years or with [≥]1 comorbidity, medically-attended visits were reduced by 52.8%, In the SSC group, patients reporting [≥]1 comorbidity had a longer median time to resolution of symptoms than those who reported no comorbidities at baseline (13 overall symptoms: 30 vs 21 days, respectively; hazard ratio [HR]=1.163 [95% CI, 0.723-1.872]; 8 cardinal symptoms: 21 vs 15 days, respectively; HR=1.283 [95% CI, 0.809-2.035]). In patients reporting [≥]1 comorbidity, median time to resolution of symptoms was shorter in the KB109 plus SSC group compared with the SSC alone group (13 overall symptoms: 30 vs 21 days, respectively; HR=1.422 [95% CI, 0.898-2.250]; 8 cardinal symptoms: 17 vs 21 days, respectively; HR=1.574 [95% CI, 0.997-2.485]). In the KB109 plus SSC group, patients aged [≥]45 years or with [≥]1 comorbidity had a shorter median time to resolution of symptoms compared with SSC alone (overall 13 symptoms: 21 vs 31 days; HR=1.597 [95% CI, 1.064-2.398]). Conclusions Results from our study show that KB109 is well tolerated among patients with mild to moderate COVID-19 MESHD. Patients with [≥]1 comorbidity had a longer duration of COVID-19 MESHD symptoms than those without comorbidities. Moreover, in patients reporting [≥]1 comorbidity or aged [≥]45 years (at-risk population), administration of KB109 plus SSC improved median time to resolution of COVID-19 MESHD-related symptoms and reduced the rate of medically-attended visits compared with SSC alone.

    IL-15 HGNC and sMAdCAM: Novel roles in COVID-19 MESHD pathogenesis

    Authors: Amit Kumar Singh; Nandini Jayant Kasarpalkar; Shilpa Dinesh Kumar Bhowmick; Gaurav Paradkar; Mayur Talreja; Karan Shah; Abhishek Tiwari; Harsha Chandrashekhar Palav; Snehal Nagendra Kaginkar; Rajiv Kulkarni; Ashwini Patil; Varsha Kalsurkar; Sachee Agrawal; Jayanthi Shastri; Rajesh Dere; Ramesh Bharmal; Smita D Mahale; Vikrant M Bhor; Vainav Patel

    doi:10.1101/2021.03.25.21254215 Date: 2021-03-29 Source: medRxiv

    Immune cell dysregulation and lymphopenia MESHD characterize COVID-19 MESHD pathology in moderate to severe disease. While underlying inflammatory factors have been extensively studied, homeostatic and mucosal migratory signatures remain largely unexplored as causative factors. In this study we evaluated the association of circulating IL-6 HGNC, soluble mucosal addressin cell adhesion molecule (sMAdCAM) and IL-15 HGNC with cellular dysfunction characterizing mild and hypoxemic stages of COVID-19 MESHD. A cohort of SARS-CoV-2 infected MESHD individuals (n=125) at various stages of disease progression together with healthy controls (n=16) were recruited from COVID Care Centres (CCCs) across Mumbai, India. Multiparametric flow cytometry was used to perform in-depth immune subset characterization and to measure plasma IL-6 HGNC levels. sMAdCAM, IL-15 HGNC levels were quantified using ELISA. Distinct depletion profiles, with relative sparing of CD8 HGNC effector memory and CD4 HGNC+ regulatory T cells was observed in hypoxemic disease MESHD within the lymphocyte compartment. An apparent increase in the frequency of intermediate monocytes characterized both mild as well as hypoxemic disease MESHD. IL-6 HGNC levels inversely correlated with those of sMAdCAM and both markers showed converse associations with observed lympho-depletion suggesting opposing roles in pathogenesis. Interestingly, IL-15 HGNC, a key cytokine involved in lymphocyte activation and homeostasis, was detected in symptomatic individuals but not in healthy controls or asymptomatic cases. Further, negative association of plasma IL-15 HGNC with depleted T, B and NK subsets suggested a compensatory production of this cytokine in response to the profound lymphopenia MESHD. Finally, higher levels of plasma IL-15 HGNC and IL-6 HGNC, but not sMAdCAM, were associated with longer duration of hospitalization.

    Preliminary report on SARS-CoV-2 Spike PROTEIN mutation T478K

    Authors: Simone Di Giacomo; Daniele Mercatelli; Amir Rakhimov; Federico M Giorgi

    doi:10.1101/2021.03.28.437369 Date: 2021-03-29 Source: bioRxiv

    Several SARS-CoV-2 variants have emerged, posing a renewed threat to COVID-19 MESHD containment and to vaccine and drug efficacy. In this study, we analyzed more than 820,000 SARS-CoV-2 genomic sequences deposited up to March 26, 2021 and identified a novel T478K mutation located on the SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN protein. The mutation is structurally located in the region of interaction with human receptor ACE2 HGNC and was detected in 4,214 distinct cases. We show that T478K has appeared and risen in frequency since January 2021, predominantly in Mexico and North America, but we could also detect it in several European countries.

    A lipid nanoparticle RBD-hFc mRNA vaccine protects hACE2 HGNC transgenic mice against lethal SARS-CoV-2 infection MESHD

    Authors: Uri Elia; Shahar Rotem; Srinivas Ramishetti; David Gur; Moshe Aftalion; Adi Bercovich-Kinori; Ron Alcalay; Efi Makdasi; Theodor Chitlaru; Ronit Rosenfeld; Tomer Israely; Sharon Melamed; Inbal Abutbul Ionita; Dganit Danino; Dan Peer; Ofer Cohen

    doi:10.1101/2021.03.29.436639 Date: 2021-03-29 Source: bioRxiv

    The current global COVID-19 pandemic MESHD led to an unprecedented effort to develop effective vaccines against SARS-CoV-2. mRNA vaccines were developed very rapidly during the last year, and became the leading immunization platform against the virus, with highly promising phase-3 results and remarkable efficacy data. Since most animal models are not susceptible to SARS CoV-2 infection MESHD, pre-clinical studies are often limited to infection-prone animals such as hamsters and non-human primates. In these animal models, SARS-CoV-2 infection MESHD results in viral replication and a mild disease disease MESHD. Therefore, the protective efficacy of the vaccine in these animals is commonly evaluated by its ability to elicit immunologic responses, diminish viral replication and prevent weight loss MESHD. Our lab recently reported the design of a SARS-CoV-2 human Fc-conjugated receptor-binding domain (RBD-hFc) mRNA vaccine delivered via lipid nanoparticles (LNPs). These experiments demonstrated the development of a robust and specific immunologic response in RBD-hFc mRNA- vaccinated BALB/c mice. In the current study, we evaluated the protective effect of this RBD-hFc mRNA vaccine by employing the K18- hACE2 HGNC mouse model. We report that administration of RBD-hFc mRNA vaccine to K18- hACE2 HGNC mice led to a robust humoral response comprised of both binding and neutralizing antibodies. In accordance with the recorded immunologic immune response, 70% of vaccinated mice were protected against a lethal dose (3000 plaque forming units) of SARS-CoV-2, while all control animals succumbed to infection. To the best of our knowledge, this is the first non-replicating mRNA vaccine study reporting protection of K18- hACE2 HGNC against a lethal SARS-CoV-2 infection MESHD.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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