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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (289)

ProteinN (99)

NSP5 (59)

ComplexRdRp (26)

NSP3 (17)


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    Mechanism of a COVID-19 MESHD nanoparticle vaccine candidate that elicits a broadly neutralizing antibody response to SARS-CoV-2 variants

    Authors: Yi-Nan Zhang; Jennifer Paynter; Tatiana Fourfouris; Cindy Sou; Timothy Ngo; Linling He; Jiang Zhu

    doi:10.1101/2021.03.26.437274 Date: 2021-03-27 Source: bioRxiv

    Vaccines against severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) are essential for combating the coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic. Neutralizing antibody responses to the original Wuhan-Hu-1 strain that were generated during infection and vaccination showed lower effectiveness against variants of concern. Here, we demonstrated that mouse plasma induced by protein nanoparticles that present rationally designed S2G{Delta}HR2 spikes can neutralize the B.1.1.7, B.1.351, and P.1 variants with comparable titers. The mechanism of nanoparticle vaccine-induced immunity was examined in mice for an I3-01v9 60-mer that presents 20 stabilized spikes. Compared with the soluble spike, this nanoparticle showed 6-fold longer retention, 4-fold greater presentation on follicular dendritic cell dendrites, and 5-fold higher germinal center reactions in lymph node follicles. Intact nanoparticles in lymph node tissues were visualized by transmission electron microscopy. In conclusion, spike-presenting protein nanoparticles that induce robust long-lived germinal centers may provide a vaccine solution for emerging SARS-CoV-2 variants.

    High Throughput Virtual Screening and Validation of a SARS-CoV-2 Main Protease PROTEIN Non-Covalent Inhibitor

    Authors: Austin Clyde; Stephanie Galanie; Daniel W. Kneller; Heng Ma; Yadu Babuji; Ben Blaiszik; Alexander Brace; Thomas Brettin; Kyle Chard; Ryan Chard; Leighton Coates; Ian Foster; Darin Hauner; Vilmos Kertesz; Neeraj Kumar; Hyungro Lee; Zhuozhao Li; Andre Merzky; Jurgen G. Schmidt; Li Tan; Mikhail Titov; Anda Trifan; Matteo Turilli; Hubertus Van Dam; Srinivas C. Chennubhotla; Shantenu Jha; Andrey Kovalevsky; Arvind Ramanathan; Marti Head; Rick Stevens

    doi:10.1101/2021.03.27.437323 Date: 2021-03-27 Source: bioRxiv

    Despite the recent availability of vaccines against the acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), the search for inhibitory therapeutic agents has assumed importance especially in the context of emerging new viral variants. In this paper, we describe the discovery of a novel non-covalent small-molecule inhibitor, MCULE-5948770040, that binds to and inhibits the SARS-Cov-2 main protease PROTEIN ( Mpro PROTEIN) by employing a scalable high throughput virtual screening (HTVS) framework and a targeted compound library of over 6.5 million molecules that could be readily ordered and purchased. Our HTVS framework leverages the U.S. supercomputing infrastructure achieving nearly 91% resource utilization and nearly 126 million docking calculations per hour. Downstream biochemical assays validate this Mpro PROTEIN inhibitor with an inhibition constant (Ki) of 2.9 uM [95% CI 2.2, 4.0]. Further, using room-temperature X-ray crystallography, we show that MCULE-5948770040 binds to a cleft MESHD in the primary binding site of Mpro PROTEIN forming stable hydrogen bond and hydrophobic interactions. We then used multiple s-timescale molecular dynamics ( MD MESHD) simulations, and machine learning (ML) techniques to elucidate how the bound ligand alters the conformational states accessed by Mpro PROTEIN, involving motions both proximal and distal to the binding site. Together, our results demonstrate how MCULE-5948770040 inhibits Mpro PROTEIN and offers a springboard for further therapeutic design.

    Seroprevalence of antibodies against SARS-CoV-2 virus in the adult Norwegian population, winter 2020/2021: pre-vaccination period

    Authors: Erik Eik Anda; Tonje Braaten; Kristin Benjaminsen Borch; Therese Haugdahl Nost; Sairah Lai Fa Chen; Marko Lukic; Eiliv Lund; Frode Forland; David Leon; Brita Askeland Winje; Anne-Marte Bakken Kran; Mette Kalager; Fridtjof Lund Johansen; Torkjel Manning Sandanger

    doi:10.1101/2021.03.23.21253730 Date: 2021-03-26 Source: medRxiv

    Since early 2020, over 123 million people worldwide have been diagnosed with coronavirus disease MESHD ( Covid-19 MESHD), but the true number of infections with severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is undoubtedly higher. The seroprevalence of antibodies against SARS-CoV-2 can provide crucial epidemiological information about the extent of infections independent of virologically detected case numbers. There is no large population-based SARS-CoV-2 seroprevalence survey from Norway; thus we estimated SARS-CoV-2 seroprevalence in Norway before the introduction of vaccines and described its distribution across demographic groups. In November-December 2020, a total of 110,000 people aged 16 years or older were randomly selected from the National Population Register and invited to complete a questionnaire and provide a dried blood spot (DBS) sample. The response rate was 30%; compliance rate for return of DBS samples was 88%. The national weighted and adjusted seroprevalence was 0.9% (confidence interval 0.7-1.0). Seroprevalence was highest among those aged 16-19 years (1.9%, 0.9-2.9), those born outside the Nordic countries 1.4% (1.0-1.9), and in the counties of Oslo 1.7 % (1.2-2.2) and Vestland 1.4% (0.9-1.8). The ratio of SARS-CoV-2 seroprevalence (0.9) to the cumulative incidence of virologically detected cases by mid-December 2020 (0.8%) was slightly above one. SARS-CoV-2 seroprevalence was low before the introduction of vaccines in Norway and was comparable to virologically detected cases, indicating that most cases in the first 10 months of the pandemic were detected. Preventive measures including contact tracing have been effective, people are complying with social distancing recommendations, and local efforts to contain outbreaks have been essential.

    ACE HGNC gene variants rise the risk of severe COVID-19 MESHD in patients with hypertension MESHD, dyslipidemia MESHD or diabetes MESHD. A pilot study

    Authors: María Íñiguez; Patricia Pérez-Matute; Pablo Villoslada-Blanco; Emma Recio-Fernandez; Diana Ezquerro-Perez; Jorge Alba; M.Lourdes Ferreira-Laso; José A. Oteo

    doi:10.1101/2021.03.24.21253576 Date: 2021-03-26 Source: medRxiv

    Coronavirus disease MESHD 19 ( COVID-19 MESHD) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD continues to scale and threaten human health and public safety. It is essential to identify those risk factors that lead to a poor prognosis of the disease. A predisposing host genetic background could be one of these factors that explain the interindividual variability to COVID-19 MESHD severity. Thus, we have studied whether the rs4341 and rs4343 polymorphisms of the angiotensin converting enzyme HGNC ( ACE HGNC) gene, key regulator of the renin-aldosterone-angiotensin system (RAAS), could explain the different outcomes of 128 COVID-19 MESHD patients with diverse degree of severity (33 asymptomatic or mildly asymptomatic, 66 hospitalized in the general ward, and 29 admitted to the ICU). We found that G allele of rs4341 and rs4343 was associated with severe COVID-19 MESHD in hypertensive MESHD patients, independently of gender (p<0.05). G-carrier genotypes of both polymorphisms were also associated with higher mortality (p< 0.05) and higher severity of COVID-19 MESHD in dyslipidemic (p<0.05) and type 2 diabetic MESHD patients (p< 0.01). In conclusion, our preliminary study suggests that the G-containing genotypes of rs4341 and rs4343 confer an additional risk of adverse COVID-19 MESHD prognosis. Thus, rs4341 and rs4343 polymorphisms of ACE HGNC could be predictive markers of severity of COVID-19 MESHD in those patients with hypertension MESHD, dyslipidemia MESHD or diabetes MESHD. The knowledge of these genetic data could contribute to precision management of SARS-Cov2 infected MESHD patients when admitted to hospital.

    Estimating the impact of interventions against COVID-19 MESHD: from lockdown to vaccination

    Authors: James Thompson; Stephen Wattam

    doi:10.1101/2021.03.21.21254049 Date: 2021-03-26 Source: medRxiv

    Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is an infectious disease of humans caused by severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2). Since the first case was identified in China in December 2019 the disease has spread worldwide, leading to an ongoing pandemic. In this article, we present a detailed agent-based model of COVID-19 MESHD in Luxembourg, and use it to estimate the impact, on cases and deaths, of interventions including testing, contact tracing, lockdown, curfew and vaccination. Our model is based on collation, with agents performing activities and moving between locations accordingly. The model is highly heterogeneous, featuring spatial clustering, over 2000 behavioural types and a 10 minute time resolution. The model is validated against COVID-19 MESHD clinical monitoring data collected in Luxembourg in 2020. Our model predicts far fewer cases and deaths MESHD than the equivalent equation-based SEIR model. In particular, with $R_0 = 2.45$, the SEIR model infects 87% of the resident population while our agent-based model results, on average, in only around 23% of the resident population infected. Our simulations suggest that testing and contract tracing reduce cases substantially, but are much less effective at reducing deaths. Lockdowns appear very effective although costly, while the impact of an 11pm-6am curfew is relatively small. When vaccinating against a future outbreak, our results suggest that herd immunity can be achieved at relatively low levels, with substantial levels of protection achieved with only 30% of the population immune. When vaccinating in midst of an outbreak, the challenge is more difficult. In this context, we investigate the impact of vaccine efficacy, capacity, hesitancy and strategy. We conclude that, short of a permanent lockdown, vaccination is by far the most effective way to suppress and ultimately control the spread of COVID-19 MESHD.

    A rapid assessment of wastewater for genomic surveillance of SARS-CoV-2 variants at sewershed scale in Louisville, KY

    Authors: Joshua Fuqua; Eric Rouchka; Sabine Waigel; Kevin Sokoloski; Donghoon Chung; Wolfgang Zacharias; Mei Zhang; Julia Chariker; Daymond Talley; Ian Santisteban; Arvind Vasrsani; Sarah Moyer; Rochelle H Holm; Ray Yeager; Ted R Smith; Aruni Bhatnagar

    doi:10.1101/2021.03.18.21253604 Date: 2021-03-26 Source: medRxiv

    The successful viral detection of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) RNA in wastewater at various pooled scales (1-4) and discovery in the USA of B.1.1.7 , B.1.351 and P.1 variants (5), has led to an interest in developing reliable population-level wastewater viral genomic surveillance. The diversity of SARS-CoV-2 sequences reported to be circulating in the USA, have been determined by sequencing clinical samples; however, these variants can also be surveilled by sequencing wastewater samples (6-9). As of March 2021, the variants of concern - B.1.1.7, B.1.351, and P.1 have been widely detected in clinical samples from 47 states in the USA. In Kentucky, only five clinical cases have been linked to the presence of these variants (5),which could indicate incomplete surveillance. Broadening the application of genomic surveillance using wastewater in the community could enhance SARS-CoV-2 variant population monitoring. In this communication, we report on the genomic surveillance of SARS-CoV-2 using wastewater samples in Jefferson County, KY. Samples were collected from manholes and treatment facilities, covering populations of 8,000 to 350,000 people (Table 1). RNA isolated from wastewater samples was used to quantify SARS-CoV-2 and analyze the genetic variation through high-throughput sequencing (See Supplementary Methods). Bioinformatics approaches were used to rapidly identify single nucleotide genetic alterations, which were compared with known variants of interest and concern. In February 2021, we analyzed seven wastewater samples for SARS-CoV-2 genomic surveillance (Figure 1). We did not detect genetic variations indicative of any current variant of concern, beyond the widespread D614G spike protein PROTEIN mutation (Supplementary Methods Tables 2-5). In all samples, we identified at least four of ten mutations consistent with the presence of the variant of interest B.1.429, and one sample contained seven of ten mutations (Table 2). The B.1.429 variant was confirmed in patient samples in Kentucky in January 2021 (10), and a single patient in the study area was reported to be positive for B.1.1.7 on February 9, 2021 (11). With our current metrics we flagged sites 833, 891, and Treatment plant #2 for potential presence of variant B.1.429 (3/7 sites). Differences in the scale of sample pooling in the community revealed unanticipated inconsistencies in variant representation. Specifically, variants observed in smaller catchment areas, such as neighborhood manhole locations, were not observed in downstream treatment plants, suggesting catchment size or population could impact the ability to detect diversity. Given the highly variable viral genome sequence coverage recovered from wastewater samples, there is an urgent need to develop a set of consistent thresholds constituting positive/negative presence of a variant. Monitoring SARS-CoV-2 variants in wastewater may warn of an emerging variant of concern and identify variant dominance occurring when a new variant is introduced in a community. Wastewater genetic monitoring may be particularly useful in the context of limited clinical sample sequencing capacity because a broad perspective on the genetic diversity can be obtained from a few samples. To develop comprehensive epidemiological frameworks required to guide policy, population-level wastewater surveillance of viral genetic diversity should be complemented by clinical sample testing.

    Pregnancy and risk of COVID-19 MESHD

    Authors: Maria Magnus; Laura Oakley; Hakon K Gjessing; Olof Stephansson; Hilde M Engjom; Ferenc Macsali; Petur B Juliusson; Anne-Marie Nybo Andersen; Siri E Haberg

    doi:10.1101/2021.03.22.21254090 Date: 2021-03-26 Source: medRxiv

    Background: Studies report that pregnant women with coronavirus disease 2019 MESHD ( COVID-19 MESHD) are at increased risk of severe disease, intensive-care and death. Whether pregnant women in general are more susceptible of contracting severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is unclear. Methods: Linked registry-data on all women ages 15 to 45 living in Norway on March 1st, 2020 (N=1,033,699) were used in Cox regression models to estimate hazard ratios (HR) comparing pregnant to non-pregnant women, of having a positive test for SARS-CoV-2, a diagnosis of COVID-19 MESHD in specialist healthcare, or hospitalization with COVID-19 MESHD, adjusting for age, marital status, education, income, country of birth and underlying medical conditions. Results: Compared to non-pregnant women, pregnant women had a similar risk of a positive SARS-CoV-2 test (adjusted HR, 0.99; 95% confidence interval [CI], 0.92 to 1.07), a higher risk of a COVID-19 MESHD diagnosis in specialist care (HR, 3.46; 95% CI, 2.89 to 4.14), and to be hospitalized (HR, 4.70; 95% CI, 3.51 to 6.30). Pregnant women were in general not more likely to be tested for SARS-CoV-2. Pregnant women born outside Scandinavia were less likely to be tested, but at higher risk of a positive test (HR, 2.37; 95% CI, 2.51 to 8.87) and of hospitalization with COVID-19 MESHD (HR, 4.72; 95% CI, 2.51 to 8.87) than pregnant Scandinavian born women. Conclusion: Pregnant women were not more likely to be infected with SARS-CoV-2. However, pregnant women with COVID-19 MESHD, especially those born outside of Scandinavia, were more likely to receive specialist care and to be hospitalized.

    Multiplex Antibody Analysis of IgM, IgA HGNC and IgG to SARS-CoV-2 in Saliva and Serum from Infected Children and their Close Contacts

    Authors: Carlota Dobano; Selena Alonso; Marta Vidal; Alfons Jimenez; Rocio Rubio; Rebeca Santano; Diana Barrios; Gemma Pons Tomas; Maria Mele Casas; Maria Hernandez Garcia; Monica Girona-Alarcon; Laura Puyol; Natalia Rodrigo Melero; Carlo Carolis; Aleix Garcia-Miquel; Elisenda Bonet-Carne; Joana Claverol; Marta Cubells; Claudia Fortuny; Victoria Fumado; Anna Codina; Quique Bassat; Carmen Munoz-Almagro; Mariona Fernandez de Sevilla; Eduard Gratacos; Luis Izquierdo; Juan Jose Garcia-Garcia; Ruth Aguilar; Iolanda Jordan; Gemma Moncunill

    doi:10.1101/2021.03.22.21254120 Date: 2021-03-26 Source: medRxiv

    COVID-19 MESHD affects children to a lesser extent than adults but they can still get infected and transmit SARS-CoV-2 to their contacts. Field deployable non-invasive sensitive diagnostic techniques are needed to evaluate the infectivity dynamics of the coronavirus in pediatric populations and guide public health interventions. We evaluated the utility of high-throughput Luminex-based assays applied to saliva samples to quantify IgM, IgA HGNC and IgG antibodies against five SARS-CoV-2 spike MESHD SARS-CoV-2 spike PROTEIN (S) and nucleocapsid (N PROTEIN) antigens in the context of a contacts and infectivity longitudinal MESHD study. We compared the antibody levels obtained in saliva versus serum/plasma samples from a group of children and adults tested weekly by RT-PCR over 35 days and diagnosed as positive (n=58), and a group of children and adults who consistently tested negative over the follow up period (n=61), in the Summer of 2020 in Barcelona, Spain. Antibody levels in saliva samples from individuals with confirmed RT-PCR diagnosis of SARS-CoV-2 infection MESHD were significantly higher than in negative individuals and correlated with those measured in sera/plasmas. Higher levels of anti-S IgG were found in asymptomatic individuals that could indicate protection against disease in infected MESHD individuals. Higher anti-S IgG and IgM levels in serum/plasma and saliva, respectively, in infected children compared to infected adults could also be related to stronger clinical immunity in them. Among infected children, males had higher levels of saliva IgG to N and RBD than females. Despite overall correlation, individual clustering analysis suggested that responses that may not be detected in blood could be patent in saliva, and vice versa, and therefore that both measurements are complementary. In addition to serum/plasma, measurement of SARS-CoV-2-specific saliva antibodies should be considered as a complementary non-invasive assay to better estimate the percentage of individuals who have experienced coronavirus infection MESHD. Saliva antibody detection could allow determining COVID-19 MESHD prevalence in pediatric populations, alternative to bleeding MESHD or nasal swab, and serological diagnosis following vaccination.

    Detection of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) in a fourplex real-time quantitative reverse transcription-PCR assays.

    Authors: Mathieu Durand; Philippe Thibault; Simon Levesque; Ariane Brault; Alex Carignan; Louis Valiquette; Philippe Martin; Simon Labbe

    doi:10.1101/2021.03.23.21254196 Date: 2021-03-26 Source: medRxiv

    The early diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections MESHD is required to identify and isolate contagious patients to prevent further transmission of the coronavirus disease 2019 MESHD ( COVID-19 MESHD). In this study, we present a multitarget real-time TaqMan reverse transcription PCR (rRT-PCR) assay for the quantitative detection of SARS-CoV-2 and some of its circulating variants harboring mutations that give SARS-CoV-2 a selective advantage. Seven different primer-probe sets that included probes containing locked nucleic acid (LNA) nucleotides were designed to amplify specific wild-type and mutant sequences in Orf1ab, Envelope (E), Spike (S), and Nucleocapsid (N PROTEIN) genes. Furthermore, a newly developed primer-probe set targeted human beta-2 microglobulin HGNC ( B2M HGNC) as a highly sensitive internal control for RT efficacy. All singleplex and fourplex assays detected less than or equal to 14 copies/reaction of quantified synthetic RNA transcripts, with a linear amplification range of 9 logarithmic orders. Primer-probe sets for detection of SARS-CoV-2 exhibited no false-positive amplifications with other common respiratory pathogens, including human coronaviruses NL63, 229E, OC43, and HKU-1. Given the emergence of SARS-CoV-2 variants and their rapid spread in some populations, fourplex rRT-PCR assay containing four primer-probe sets represents a reliable approach to detect multiple viral target sequences containing typical mutations of SARS-CoV-2 variants in a single reaction, allowing quicker detection of circulating relevant variants.

    COVID-19 MESHD antibody seroprevalence in Duhok, Kurdistan Region, Iraq: A population-based study

    Authors: Nawfal R Hussein; Amer Balatay; Ibrahim A Naqid; Shakir A Jamal; Narin A Rasheed; Alind N Ahmed; Reving S Salih; Ahmed S Mahdi; Sabeeha A Mansour; Shaveen Mahdi; Nashwan Ibrahim; Dildar H Musa; Zana SM Saleem

    doi:10.1101/2021.03.23.21254169 Date: 2021-03-26 Source: medRxiv

    Abstract Objective This population-based study aimed to evaluate the seroprevalence of antibodies to SARS-CoV-2 in Duhok City, Kurdistan Region of Iraq. Methods We analyzed the national COVID-19 MESHD database that contains data regarding COVID-19 MESHD testing, management, and clinical outcomes in Duhok. For this study, different subdistricts within each district of Duhok were considered distinct clusters. Blood samples were collected from and questionnaires were administered to eligible and consenting participants who were members of different families from the subdistricts. Immunoassays were conducted to detect antibodies against SARS-CoV-2, and the associations between certain variables were investigated. Results The average number cases of COVID-19 MESHD before November 2020 was 23141 {+/-} 4364, which was significantly higher than the average number of cases between November 2020 and February 2021 (3737 {+/-} 2634; P = 0.001). A total of 743 individuals agreed to participate and were enrolled in the study. Among the participants, 465/743 (62.58%) were found to have antibodies against severe acute respiratory syndrome coronavirus 2 MESHD. Among the participants with antibodies, 262/465 (56.34%) denied having any history of COVID-19 MESHD-related symptoms. The most common symptom was fever MESHD (81.77%), followed by myalgia MESHD (81.28%). We found that antibody levels increased steadily with age (Pearson correlation coefficient = 0.117; P = 0.012). A significant association was found between antibody levels and the presence of symptoms (P = 0.023; odds ratio = 1.0023; 95% confidence interval = 1.0002-1.0061). Conclusions A significant reduction in the number of COVID-19 MESHD cases was observed. This might be due to the high prevalence of SARS-CoV-2 antibodies in Duhok. However, infection-prevention measures should be followed as it remains unclear whether acquired immunity is protective against reinfection. It expected that the infection rates during the next wave will not be as high as the first wave due to the high infection rate in the society.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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