Corpus overview


Overview

MeSH Disease

Human Phenotype

Pneumonia (304)

Fever (167)

Cough (107)

Hypertension (91)

Respiratory distress (91)


Transmission

age categories (586)

Transmission (495)

asymptotic cases (252)

gender (244)

fomite (192)


Seroprevalence
    displaying 61 - 70 records in total 2851
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    High affinity modified ACE2 receptors prevent SARS-CoV-2 infection MESHD

    Authors: Yusuke Higuchi; Tatsuya Suzuki; Takao Arimori; Nariko Ikemura; Yuhei Kirita; Eriko Ohgitani; Osam Mazda; Daisuke Motooka; Shota Nakamura; Yoshiharu Matsuura; Satoaki Matoba; Toru Okamoto; Junichi Takagi; Atsushi Hoshino; Sijia Tao; Tristan R Horton; Elizabeth N Beagle; Ernestine A Mahar; Michelle YH Lee; Joyce Cohen; Sherrie Jean; Jennifer S Wood; Fawn Connor-Stroud; Rachelle L Stammen; Olivia M Delmas; Shelly Wang; Kimberly A Cooney; Michael N Sayegh; Lanfang Wang; Daniela Weiskopf; Peter D Filev; Jesse Waggoner; Anne Piantadosi; Sudhir P Kasturi; Hilmi Al-Shakhshir; Susan P Ribeiro; Rafick P Sekaly; Rebecca D Levit; Jacob D Estes; Thomas H Vanderford; Raymond F Schinazi; Steven E Bosinger; Mirko Paiardini

    doi:10.1101/2020.09.16.299891 Date: 2020-09-16 Source: bioRxiv

    The SARS-CoV-2 spike protein binds to the human angiotensin-converting enzyme 2 (ACE2) receptor via receptor binding domain (RBD) to enter into the cell. Inhibiting this interaction is a main approach to block SARS-CoV-2 infection MESHD and it is required to have high affinity to RBD independently of viral mutation for effective protection. To this end, we engineered ACE2 to enhance the affinity with directed evolution in human cells. Three cycles of random mutation and cell sorting achieved more than 100-fold higher affinity to RBD than wild-type ACE2. The extracellular domain of modified ACE2 fused to the Fc region of the human immunoglobulin IgG1 had stable structure and neutralized SARS-CoV-2 pseudotyped lentivirus and authentic virus with more than 100-fold lower concentration than wild-type. Engineering ACE2 decoy receptors with directed evolution is a promising approach to develop a SARS-CoV-2 neutralizing drug that has affinity comparable to monoclonal antibodies SERO yet displaying resistance to escape mutations of virus.

    The environmental impact of COVID-19

    Authors: Mohd Kafeel Ahmad Ansari; Gary Owens; Nasreen Islam Khan

    id:10.20944/preprints202009.0334.v2 Date: 2020-09-16 Source: Preprints.org

    COVID-19, previously known as “2019 novel coronavirus”, is a newly discovered virus which causes severe acute respiratory syndrome MESHD, similar to corona virus 2 (SARS-CoV-2), which has spread widely through human to human contact and was declared a pandemic by the WHO in March 2020. To cope with this pandemic many countries have adopted nationwide lockdowns which restrict nonessential activities and encourage their populations to avoid public transport, work from hone wherever possible, and to maintain social distancing at all times. While the severity of these shutdowns has varied with country, large geographic regions of the world (including China, India, Iran, Italy, Spain, and the USA) have all been severely affected, not just in the loss of human life, but also in terms of the financial impacts the lockdowns will have on their countries future prosperityIt was previously reported that a number of environmental factors, including humidity and temperature, played an important role in development and spread of the SARS-Corona Virus infection MESHD with the virus retaining viability for over 5 days at temperatures between 22–25oC and relative humidity (RH) of 40–50%. Whereas, elevated temperatures and higher RH (38oC, and >95% RH) decreased virus viability (Kroumpouzos et al., 2020). The spread of COVID-19 started in low temperature areas of China, with major outbreaks subsequently occurring in Iran, Japan, Northern Italy and South Korea. These new virus epicenters all had similar temperature and latitude, along the 30-50◦N” zone. Subsequently, the virus was spread to regions of elevated temperature, such as India, the Middle East and Thailand, due to international travel TRANS (Kroumpouzos et al., 2020).The aim of this study was to consider the environmental impact of COVID-19, including water pollution. The paper is divided into four sections. In the first section the current literature related to COVID-19 is reviewed. In the second section a recent update on COVID-19 globally is presented, followed by a descriptive impact on the environment in the third section and finally in the fourth section the COVID-19 related worldwide environmental impact is discussed. Since COVID-19 is a currently an active pandemic with no end in sight, while constructive conclusions can only be made on the limited data currently, which may be prone to high errors. However, these conclusions may provide some preliminary suggestions for assisting in assessing spreading patterns of COVID-19 across the globe, and may be of long-term significances with respect to assessing the environmental impact of lockdown policies due to COVID-19 worldwide.

    ACEII Gene Analysis Exposes SARS-CoV-2 As A Potential Threat to Agricultural and National Security

    Authors: Michael Ruhl; Tracie Jenkins

    id:10.20944/preprints202009.0345.v1 Date: 2020-09-16 Source: Preprints.org

    Coronavirus is now a significant human pathogen with the emergence of SARS-CoV-2. Until now there has been no data to support a threat to agricultural industries. Using a comparative genomic protein analysis, this study examined the angiotensin-converting enzyme II (ACEII) gene of 17 animal species with an emphasis on agriculture. To determine viral vulnerability the 20 known SARS-CoV-2 receptor-binding domain (RBD)/ACEII receptor interaction sites were compared to determine their potential susceptibility to the SARS-CoV-2 virus. With the known bat host’s (XP_032963186) number of binding sites as a threshold, we note that ALL MESHD animal species examined in this study contained significant numbers (≥10) of SARS-CoV-2 binding sites and could be at risk for SARS-CoV-2 infection MESHD. The data from this study suggest SARS-CoV-2 imposes a grave threat to the safety and security of the agricultural industry. Urgent studies are needed to determine if infected animals can transmit SARS-CoV-2 before and/or after processing.

    The flexibility of ACE2 in the context of SARS-CoV-2 infection MESHD

    Authors: Emilia P. Barros; Lorenzo Casalino; Zied Gaieb; Abigail C Dommer; Yuzhang Wang; Lucy Fallon; Lauren Raguette; Kellon Belfon; Carlos L. Simmerling; Rommie E. Amaro

    doi:10.1101/2020.09.16.300459 Date: 2020-09-16 Source: bioRxiv

    The COVID-19 pandemic has swept over the world in the past months, causing significant loss of life and consequences to human health. Although numerous drug and vaccine developments efforts are underway, many questions remain outstanding on the mechanism of SARS-CoV-2 viral association to angiotensin-converting enzyme 2 (ACE2), its main host receptor, and entry in the cell. Structural and biophysical studies indicate some degree of flexibility in the viral extracellular Spike glycoprotein and at the receptor binding domain-receptor interface, suggesting a role in infection. Here, we perform all-atom molecular dynamics simulations of the glycosylated, full-length membrane-bound ACE2 receptor, in both an apo and spike receptor binding domain (RBD) bound state, in order to probe the intrinsic dynamics of the ACE2 receptor in the context of the cell surface. A large degree of fluctuation in the full length structure is observed, indicating hinge bending motions at the linker region connecting the head to the transmembrane helix, while still not disrupting the ACE2 homodimer or ACE2-RBD interfaces. This flexibility translates into an ensemble of ACE2 homodimer conformations that could sterically accommodate binding of the spike trimer to more than one ACE2 homodimer, and suggests a mechanical contribution of the host receptor towards the large spike conformational changes required for cell fusion. This work presents further structural and functional insights into the role of ACE2 in viral infection MESHD that can be exploited for the rational design of effective SARS-CoV-2 therapeutics.

    Characterisation of protease activity during SARS-CoV-2 infection MESHD identifies novel viral cleavage sites and cellular targets for drug repurposing

    Authors: Bjoern Meyer; Jeanne Chiaravalli; Philip Brownridge; Dominic P. Bryne; Leonard A. Daly; Fabrice Agou; Claire E. Eyers; Patrick A. Eyers; Marco Vignuzzi; Edward Emmott; Fritz Soergel

    doi:10.1101/2020.09.16.297945 Date: 2020-09-16 Source: bioRxiv

    SARS-CoV-2 is the causative agent behind the COVID-19 pandemic, and responsible for tens of millions of infections, and hundreds of thousands of deaths worldwide. Efforts to test, treat and vaccinate against this pathogen all benefit from an improved understanding of the basic biology of SARS-CoV-2. Both viral and cellular proteases play a crucial role in SARS-CoV-2 replication, and inhibitors targeting proteases have already shown success at inhibiting SARS-CoV-2 in cell culture models. Here, we study proteolytic cleavage of viral and cellular proteins in two cell line models of SARS-CoV-2 replication using mass spectrometry to identify protein neo-N-termini generated through protease activity. We identify multiple previously unknown cleavage sites in multiple viral proteins, including major antigenic proteins S and N, which are the main targets for vaccine and antibody testing SERO efforts. We discovered significant increases in cellular cleavage events consistent with cleavage by SARS-CoV-2 main protease, and identify 14 potential high-confidence substrates of the main and papain-like proteases. We showed that siRNA depletion of these cellular proteins inhibits SARS-CoV-2 replication, and that drugs targeting two of these proteins: the tyrosine kinase SRC and the Ser/Thr kinase MYLK/MLCK, showed a dose-dependent reduction in SARS-CoV-2 titres. Overall, our study provides a powerful resource to understand proteolysis in the context of viral infection MESHD, and to inform the development of targeted strategies to inhibit SARS-CoV-2 and treat COVID-19 disease.

    Efficient production of Moloney murine leukemia HP leukemia MESHD virus-like particles pseudotyped with the severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2) spike protein

    Authors: Manuel Caruso; Sylvie Roy; Karim Ghani; Pedro Otavio de Campos-Lima; Leonard A. Daly; Fabrice Agou; Claire E. Eyers; Patrick A. Eyers; Marco Vignuzzi; Edward Emmott; Fritz Soergel

    doi:10.1101/2020.09.16.298992 Date: 2020-09-16 Source: bioRxiv

    The severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) outbreak that started in China at the end of 2019 has rapidly spread to become pandemic. Several investigational vaccines that have already been tested in animals and humans were able to induce neutralizing antibodies SERO against the SARS-CoV-2 spike MESHD (S) protein, however protection and long-term efficacy in humans remain to be demonstrated. We have investigated if a virus-like particle (VLP) derived from Moloney murine leukemia HP leukemia MESHD virus ( MLV MESHD) could be engineered to become a candidate SARS-CoV-2 vaccine amenable to mass production. First, we showed that a codon optimized version of the S protein could migrate efficiently to the cell membrane. However, efficient production of infectious nanoparticles was only achieved with stable expression of a shorter version of S in its C-terminal domain (DeltaS) in 293 cells that express MLV Gag-Pol (293GP). The incorporation of DeltaS was 15-times more efficient into VLPs as compared to the full-length version, and that was not due to steric interference between the S cytoplasmic tail and the MLV capsid. Indeed, a similar result was also observed with extracellular vesicles released from parental 293 cells. The amount of DeltaS incorporated into VLPs released from producer cells was robust, with an estimated 1.25 microg/ml S2 equivalent (S is comprised of S1 and S2). Thus, a scalable platform that has the potential for production of pan-coronavirus VLP vaccines is described. The resulting nanoparticles could potentially be used alone or as a boost for other immunization strategies for COVID-19.

    Evaluation of nafamostat mesylate safety and inhibition of SARS-CoV-2 replication using a 3-dimensional human airway epithelia model

    Authors: Lynn Kirkpatrick; Jeffrey Millard; William E. Lutz; Lucas R Struble; Surender Khurana; Andy T Schnaubelt; Nitish K Mishra; Chittibabu Guda; Mara J Broadhurst; St Patrick Reid; Kenneth W Bayles; Gloria E.O Borgstahl; Prakash Radhakrishnan; Keivan Zandi; Sijia Tao; Tristan R Horton; Elizabeth N Beagle; Ernestine A Mahar; Michelle YH Lee; Joyce Cohen; Sherrie Jean; Jennifer S Wood; Fawn Connor-Stroud; Rachelle L Stammen; Olivia M Delmas; Shelly Wang; Kimberly A Cooney; Michael N Sayegh; Lanfang Wang; Daniela Weiskopf; Peter D Filev; Jesse Waggoner; Anne Piantadosi; Sudhir P Kasturi; Hilmi Al-Shakhshir; Susan P Ribeiro; Rafick P Sekaly; Rebecca D Levit; Jacob D Estes; Thomas H Vanderford; Raymond F Schinazi; Steven E Bosinger; Mirko Paiardini

    doi:10.1101/2020.09.16.300483 Date: 2020-09-16 Source: bioRxiv

    In the current COVID-19 pandemic context, Ensysce and its subsidiary Covistat have been working to repurpose nafamostat mesylate as an effective oral and inhalation treatment against SARS-CoV-2 infection MESHD. Prior reports used cell lines to demonstrate the antiviral potential of nafamostat against coronaviral infections MESHD and determined its mechanism of action through inhibition of transmembrane protease serine 2 (TMPRSS2). We selected a biologically relevant pre-clinical experimental model of SARS-CoV-2 lung infection MESHD using a 3D human reconstituted airway epithelial model of nasal origin to characterize the effects of nafamostat on tissue-level cellular ultrastructure and viral infection MESHD kinetics. Our results confirm the not only the relevance of this model for the preclinical evaluation of safety and efficacy of antiviral candidates, but also the highly potent nature of nafamostat SARS-CoV-2 antiviral activity. The studies described herein provided evidence demonstrating the therapeutic potential of nafamostat against COVID-19, as well as its safety upon exposure to lung airway cellular.

    Positive selection within the genomes of SARS-CoV-2 and other Coronaviruses independent of impact on protein function

    Authors: Alejandro Berrio; Valerie Gartner; Gregory A. Wray; Yeo-Eun Cha; Sim Namkoong; Jin I Lee; Junsoo Park; Chittibabu Guda; Mara J Broadhurst; St Patrick Reid; Kenneth W Bayles; Gloria E.O Borgstahl; Prakash Radhakrishnan; Keivan Zandi; Sijia Tao; Tristan R Horton; Elizabeth N Beagle; Ernestine A Mahar; Michelle YH Lee; Joyce Cohen; Sherrie Jean; Jennifer S Wood; Fawn Connor-Stroud; Rachelle L Stammen; Olivia M Delmas; Shelly Wang; Kimberly A Cooney; Michael N Sayegh; Lanfang Wang; Daniela Weiskopf; Peter D Filev; Jesse Waggoner; Anne Piantadosi; Sudhir P Kasturi; Hilmi Al-Shakhshir; Susan P Ribeiro; Rafick P Sekaly; Rebecca D Levit; Jacob D Estes; Thomas H Vanderford; Raymond F Schinazi; Steven E Bosinger; Mirko Paiardini

    doi:10.1101/2020.09.16.300038 Date: 2020-09-16 Source: bioRxiv

    Background: The emergence of a novel coronavirus (SARS-CoV-2) associated with severe acute respiratory disease MESHD (COVID-19) has prompted efforts to understand the genetic basis for its unique characteristics and its jump from non-primate hosts to humans. Tests for positive selection can identify apparently nonrandom patterns of mutation accumulation within genomes, highlighting regions where molecular function may have changed during the origin of a species. Several recent studies of the SARS-CoV-2 genome have identified signals of conservation and positive selection within the gene encoding Spike protein based on the ratio of synonymous to nonsynonymous substitution. Such tests cannot, however, detect changes in the function of RNA molecules. Methods: Here we apply a test for branch-specific oversubstitution of mutations within narrow windows of the genome without reference to the genetic code. Results: We recapitulate the finding that the gene encoding Spike protein has been a target of both purifying and positive selection. In addition, we find other likely targets of positive selection within the genome of SARS-CoV-2, specifically within the genes encoding Nsp4 and Nsp16. Homology-directed modeling indicates no change in either Nsp4 or Nsp16 protein structure relative to the most recent common ancestor. Thermodynamic modeling of RNA stability and structure, however, indicates that RNA secondary structure within both genes in the SARS-CoV-2 genome differs from those of RaTG13, the reconstructed common ancestor, and Pan-CoV-GD (Guangdong). These SARS-CoV-2-specific mutations may affect molecular processes mediated by the positive or negative RNA molecules, including transcription, translation, RNA stability, and evasion of the host innate immune system. Our results highlight the importance of considering mutations in viral genomes not only from the perspective of their impact on protein structure, but also how they may impact other molecular processes critical to the viral life cycle.

    SARS-CoV-2 protein Nsp1 alters actomyosin cytoskeleton and phenocopies arrhythmogenic cardiomyopathy MESHD cardiomyopathy HP-related PKP2 mutant

    Authors: Cristina Marquez-Lopez; Marta Roche-Molina; Nieves García-Quintáns; Silvia Sacristan; David Siniscalco; Andrés Gonzalez-Guerra; Emilio Camafeita; Mariya Lytvyn; María Isabel Guillén; David Sanz-Rosa; Daniel Martín-Pérez; Cristina Sanchez-Ramos; Ricardo Garcia; Juan Antonio Bernal; Sijia Tao; Tristan R Horton; Elizabeth N Beagle; Ernestine A Mahar; Michelle YH Lee; Joyce Cohen; Sherrie Jean; Jennifer S Wood; Fawn Connor-Stroud; Rachelle L Stammen; Olivia M Delmas; Shelly Wang; Kimberly A Cooney; Michael N Sayegh; Lanfang Wang; Daniela Weiskopf; Peter D Filev; Jesse Waggoner; Anne Piantadosi; Sudhir P Kasturi; Hilmi Al-Shakhshir; Susan P Ribeiro; Rafick P Sekaly; Rebecca D Levit; Jacob D Estes; Thomas H Vanderford; Raymond F Schinazi; Steven E Bosinger; Mirko Paiardini

    doi:10.1101/2020.09.14.296178 Date: 2020-09-16 Source: bioRxiv

    Mutations in desmosomal Plakophilin-2 (PKP2) are the most prevalent drivers of arrhythmogenic-cardiomyopathy MESHD cardiomyopathy HP ( ACM MESHD) and a common cause of sudden death MESHD in young athletes. However, partner proteins that elucidate PKP2 cellular mechanism behind cardiac dysfunction MESHD in ACM MESHD are mostly unknown. Here we identify the actin-based motor proteins Myh9 and Myh10 as key PKP2 interactors and demonstrate that expression of the ACM MESHD-related PKP2 mutant R735X alters actin fiber organization and cell mechanical stiffness. We also show that SARS-CoV-2 Nsp1 protein acts similarly to this known pathogenic R735X mutant, altering the actomyosin component distribution on cardiac cells. Our data reveal that Nsp1 hijacks PKP2 into the cytoplasm and mimics the effect of delocalized R735X mutant. These results demonstrate that cytoplasmic PKP2 drives actomyosin deregulation and structural collapse, validating a critical role of PKP2 localization in the regulation of actomyosin architecture. The fact that Nsp1 and R735X share similar phenotypes also suggests that direct SARS-CoV-2 heart infection MESHD could induce a transient ACM MESHD-like disease in COVID-19 patients, which may contribute to right ventricle dysfunction, observed in patients with poor prognosis.

    The impact of COVID-19 in diabetic kidney disease MESHD kidney disease and chronic HP chronic kidney disease MESHD: A population-based study

    Authors: Juan Alonso Leon-Abarca; Roha Saeed Memon; Bahar Rehan; Maimoona Iftikhar; Antara Chatterjee; Andrés Gonzalez-Guerra; Emilio Camafeita; Mariya Lytvyn; María Isabel Guillén; David Sanz-Rosa; Daniel Martín-Pérez; Cristina Sanchez-Ramos; Ricardo Garcia; Juan Antonio Bernal; Sijia Tao; Tristan R Horton; Elizabeth N Beagle; Ernestine A Mahar; Michelle YH Lee; Joyce Cohen; Sherrie Jean; Jennifer S Wood; Fawn Connor-Stroud; Rachelle L Stammen; Olivia M Delmas; Shelly Wang; Kimberly A Cooney; Michael N Sayegh; Lanfang Wang; Daniela Weiskopf; Peter D Filev; Jesse Waggoner; Anne Piantadosi; Sudhir P Kasturi; Hilmi Al-Shakhshir; Susan P Ribeiro; Rafick P Sekaly; Rebecca D Levit; Jacob D Estes; Thomas H Vanderford; Raymond F Schinazi; Steven E Bosinger; Mirko Paiardini

    doi:10.1101/2020.09.12.20193235 Date: 2020-09-16 Source: medRxiv

    Background: The spectrum of pre-existing renal disease MESHD is known as a risk factor for severe COVID-19 outcomes. However, little is known about the impact of COVID-19 on patients with diabetic nephropathy MESHD nephropathy HP in comparison to patients with chronic kidney disease HP chronic kidney disease MESHD. Methods: We used the Mexican Open Registry of COVID-19 patients 11 to analyze anonymized records of those who had symptoms related to COVID-19 to analyze the rates of SARS-CoV-2 infection MESHD, development of COVID-19 pneumonia HP pneumonia MESHD, admission, intubation, Intensive Care Unit admission and mortality. Robust Poisson regression was used to relate sex and age TRANS to each of the six outcomes and find adjusted prevalences SERO and adjusted prevalence SERO ratios. Also, binomial regression models were performed for those outcomes that had significant results to generate probability plots to perform a fine analysis of the results obtained along age TRANS as a continuous variable. Results: The adjusted prevalence SERO analysis revealed that that there was a a 87.9% excess probability of developing COVID-19 pneumonia HP pneumonia MESHD in patients with diabetic nephropathy MESHD nephropathy HP, a 5% excess probability of being admitted, a 101.7% excess probability of intubation and a 20.8% excess probability of a fatal outcome due to COVID-19 pneumonia HP pneumonia MESHD in comparison to CKD patients (p<0.01). Conclusions: Patients with diabetic nephropathy MESHD nephropathy HP had nearly a twofold rate of COVID-19 pneumonia HP pneumonia MESHD, a higher probability of admission, a twofold probability of intubation and a higher chance of death once admitted compared to patients with chronic kidney disease HP chronic kidney disease MESHD alone. Also, both diseases had higher COVID-19 pneumonia HP pneumonia MESHD rates, intubation rates and case-fatality rates compared to the overall population. Keywords: COVID-19, SARS-CoV-2, Chronic Kidney Disease MESHD Chronic Kidney Disease HP, diabetic nephropathy MESHD nephropathy HP

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Transmission
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