Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (14)

ProteinN (1)

ORF1a (1)

ORF1ab (1)


SARS-CoV-2 Proteins
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    Nasal delivery of single-domain antibodies improve symptoms of SARS-CoV-2 infection MESHD in an animal model

    Authors: Kei Haga; Reiko Takai-Todaka; Yuta Matsumura; Tomomi Takano; Takuto Tojo; Atsushi Nagami; Yuki Ishida; Hidekazu Masaki; Masayuki Tsuchiya; Toshiki Ebisudani; Shinya Sugimoto; Toshiro Sato; Hiroyuki Yasuda; Koichi Fukunaga; Akihito Sawada; Naoto Nemoto; Chihong Song; Kazuyoshi Murata; Takuya Morimoto; Kazuhiko Katayama

    doi:10.1101/2021.04.09.439147 Date: 2021-04-09 Source: bioRxiv

    The severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) that causes the disease COVID-19 MESHD can lead to serious symptoms, such as severe pneumonia MESHD, in the elderly and those with underlying medical conditions. While vaccines are now available, they do not work for everyone and therapeutic drugs are still needed particularly for treating life-threatening conditions. Here, we showed nasal delivery of a new, unmodified camelid single-domain antibody (VHH), termed K-874A, effectively inhibited SARS-CoV-2 titers MESHD in infected lungs of Syrian hamsters without causing weight loss MESHD and cytokine induction. In vitro studies demonstrated that K-874A neutralized SARS-CoV-2 in both VeroE6/ TMPRSS2 HGNC and human lung-derived alveolar MESHD organoid cells. Unlike other drug candidates, K-874A blocks viral membrane fusion rather than viral attachment. Cryo-electron microscopy revealed K-874A bound between the receptor binding domain and N-terminal domain of the virus S protein PROTEIN. Further, infected cells treated with K-874A produced fewer virus progeny that were less infective. We propose that direct administration of K-874A to the lung via a nebulizer could be a new treatment for preventing the reinfection of amplified virus in COVID-19 MESHD patients. Author summaryVaccines for COVID-19 MESHD are now available but therapeutic drugs are still needed to treat life-threatening cases and those who cannot be vaccinated. We discovered a new heavy-chain single-domain antibody that can effectively neutralize the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) that causes COVID-19 MESHD. Unlike other drug candidates, which prevent the virus from attaching to the receptor on the host cell, this new antibody acts by blocking the virus membrane from fusing with the host cell membrane. We studied the behavior of the new antibody in vitro using VeroE6/TMPRSS2 cells and human lung organoids. When delivered through the nose to infected Syrian hamsters, we found that this antibody could prevent the typical symptoms caused by SARS-CoV-2. Our results are significant because delivering simple drugs directly to infected lungs MESHD using a nebulizer could increase the potency of the drugs while reducing the risk of immune reaction that could occur if the drugs escape or are delivered through the blood stream.

    Enzalutamide, a prostate cancer MESHD therapeutic, downregulates TMPRSS2 HGNC in lung and reduces cellular entry of SARS-CoV-2

    Authors: D. A. Leach; A. Mohr; E. S. Giotis; A. M. Isac; L. L. Yates; W. S. Barclay; R. M. Zwacka; C. L. Bevan; G. N. Brooke

    doi:10.21203/ Date: 2020-12-29 Source: ResearchSquare

    The COVID-19 pandemic MESHD, caused by the novel human coronavirus SARS-CoV-2 coronavirus MESHD, attacks various organs but most destructively the lung. It has been shown that SARS-CoV-2 entry into lung cells requires two host cell surface proteins: ACE2 HGNC and TMPRSS2 HGNC. Downregulation of one or both of these is thus a potential therapeutic approach for COVID-19 MESHD TMPRSS2 HGNC is a known target of the androgen receptor HGNC, a ligand-activated transcription factor; activation of the androgen receptor HGNC increases TMPRSS2 HGNC levels in various tissues, most notably the prostate. We show here that treatment with the antiandrogen enzalutamide – a well-tolerated drug widely used in advanced prostate cancer MESHD – reduces TMPRSS2 HGNC levels in human lung cells. Further, enzalutamide treatment of mice dramatically decreased Tmprss2 levels in the lung. To determine therapeutic potential, we assessed uptake of SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN protein pseudotyped lentivirus and live SARS-CoV-2 into human lung cells and saw a significant reduction in viral entry and infection upon treatment with the antiandrogens enzalutamide and bicalutamide. In support of this new experimental data, analysis of existing datasets shows striking co-expression of AR and TMPRSS2 HGNC, including in specific lung cell types that are targeted by SARS-CoV-2. Together, the data presented provides strong evidence to support clinical trials to assess the efficacy of antiandrogens as a treatment option for COVID-19 MESHD.

    Host range projection of SARS-CoV-2: South Asia perspective

    Authors: Rasel Ahmed; Rajnee Hasan; AMAM Zonaed Siddiki; Md. Shahidul Islam; Dallas Nygard; Iryna Abramchuk; Yun-En Chung; Steffany A. L. Bennett; Mathieu Lavallee-Adam; Raul Y. Sanchez-David; Maia Kavanagh Williamson; Jack A. Hassard; Ecco Staller; Brian Hanley; Michael Osborn; Andrew D. Davidson; Wendy S. Barclay; Mohammad Mohiuddin; Naznin Sultana; Kakon Nag; Emily D Crawford; Andreas S Puschnik; Maira Phelps; Amy Kistler; Joseph L DeRisi; Jennifer A Doudna; Daniel A Fletcher; Melanie Ott

    doi:10.1101/2020.09.30.320242 Date: 2020-09-30 Source: bioRxiv

    Severe Acute Respiratory Syndrome Coronavirus 2 MESHD (SARS-CoV-2), the causing agent of Coronavirus Disease MESHD-2019 ( COVID-19 MESHD), is likely to be originated from bat and transmitted through intermediate hosts. However, the immediate source species of SARS-CoV-2 has not yet been confirmed. Here, we used diversity analysis of the angiotensin I converting enzyme 2 HGNC ( ACE2 HGNC) that serves as cellular receptor for SARS-CoV-2 and transmembrane protease serine 2 HGNC ( TMPRSS2 HGNC), which has been proved to be utilized by SARS-CoV-2 for spike PROTEIN protein priming. We also simulated the structure of receptor-binding domain of SARS-CoV-2 spike MESHD SARS-CoV-2 spike PROTEIN protein ( SARS-CoV-2 S RBD MESHD) with the ACE2 HGNCs to investigate their binding affinity to determine the potential intermediate animal hosts that could spread the SARS-CoV-2 virus to humans in South Asia. We identified cow, buffalo, goat and sheep, which are predominant species in the household farming system in South Asia that can potentially be infected by SARS-CoV-2. All the bird species studied along with rat and mouse were considered less potential to interact with SARS-CoV-2. The interaction interfaces of SARS-CoV-2 S RBD MESHD and ACE2 protein complex suggests pangolin as a potential intermediate host in SARS-CoV-2. Our results provide a valuable resource for the identification of potential hosts for SARS-CoV-2 in South Asia and henceforth reduce the opportunity for a future outbreak of COVID-19 MESHD.

    Understanding Structural Malleability of the SARS-CoV-2 Proteins and their Relation to the Comorbidities

    Authors: Sagnik Sen; Ashmita Dey; Sanghamitra Bandyopadhyay; Ujjwal Maulik; Vladimir Uversky

    doi:10.21203/ Date: 2020-09-23 Source: ResearchSquare

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent of the coronavirus disease MESHD ( CoVID-19 MESHD), is a part of the β-coronaviridae family. In comparison with two other members of this family of coronaviruses infecting humans ( SARS-CoV and Middle East Respiratory Syndrome MESHD ( MERS MESHD) CoV), SARS-CoV-2 showed the most severe effects on the entire Earth population causing world-wide CoVID-19 pandemic MESHD. SARS-CoV-2 contains five major protein classes, such as four structural proteins (Nucleocapsid (N PROTEIN), Membrane (M), Envelop (E), and Spike Glycoprotein PROTEIN (S)) and Replicase polyproteins (R), which are synthesized as two polyproteins ( ORF1a PROTEIN and ORF1ab PROTEIN) that are subsequently processed into 12 nonstructural proteins by three viral proteases. All these proteins share high sequence similarity with their SARS-CoV counterparts. Due to the severity of the current situation, most of the SARS-CoV-2-related research is focused on finding therapeutic solutions and the analysis of comorbidities during infection. However, studies on the peculiarities of the amino acid sequences of viral protein classes and their structure space analysis throughout the evolutionary time-frame are limited. At the same time, due to their structural malleability, viral proteins can be directly or indirectly associated with the dysfunctionality of the host cell proteins, which may lead to comorbidities during the infection and at the post infection stage. To fill these gaps, we conducted the evolutionary sequence-structure analysis of the viral protein classes to evaluate the rate of their evolutionary malleability. We also looked at the intrinsic disorder propensities of these viral proteins and confirmed that although they typically do not have long intrinsically disordered regions (IDRs), all of them have at least some levels of intrinsic disorder MESHD. Furthermore, short IDRs found in viral proteins are extremely effective and prioritize the proteins for host cell interactions, which may lead to host cell dysfunction. Next, the associations of viral proteins with the host cell proteins were studied, and a list of diseases which are associated with such host cell proteins was developed. Other than the usual set of diseases, we have identified some maladies, which may happen after the recovery from the infections. Comparison of the expression rates of the host cell proteins during the diseases suggested the existence of two distinct classes. First class includes proteins, which are directly associated with certain sets of diseases, where they have shared similar activities. Second class is related to the cytokine storm-mediated pro- inflammation MESHD (already known for its role in acute respiratory distress syndrome MESHD, ARDS MESHD), and neuroinflammation may trigger some of the neurological malignancies and neurodegenerative and neuropsychiatric diseases MESHD. Finally, since the transmembrane serine protease 2 ( TMPRSS2 HGNC), which is one of the leading proteins associated with the viral uptake, is an androgen-mediated protein, our study suggested that males and postmenopausal females can be more susceptible to the SARS-CoV-2 infection MESHD.

    Natural Killer cell activation, reduced ACE2 HGNC, TMPRSS2 HGNC, cytokines G-CSF HGNC, M-CSF HGNC and SARS-CoV-2-S pseudovirus infectivity by MEK HGNC inhibitor treatment of human cells

    Authors: Lanlan Zhou; Kelsey Huntington; Shengliang Zhang; Lindsey Carlsen; Eui-Young So; Cassandra Parker; Ilyas Sahin; Howard Safran; Suchitra Kamle; Chang-Min Lee; Chun-Geun Lee; Jack A. Elias; Kerry S. Campbell; Mandar T. Naik; Walter J. Atwood; Emile Youssef; Jonathan A. Pachter; Arunasalam Navaraj; Attila A. Seyhan; Olin Liang; Wafik El-Deiry

    doi:10.1101/2020.08.02.230839 Date: 2020-08-03 Source: bioRxiv

    COVID-19 MESHD affects vulnerable populations including elderly individuals and patients with cancer MESHD. Natural Killer (NK) cells and innate-immune TRAIL HGNC suppress transformed and virally-infected cells. ACE2 HGNC, and TMPRSS2 HGNC protease promote SARS-CoV-2 infectivity MESHD, while inflammatory cytokines IL-6 HGNC, or G-CSF HGNC worsen COVID-19 MESHD severity. We show MEK HGNC inhibitors (MEKi) VS-6766, trametinib and selumetinib reduce ACE2 HGNC expression in human cells. Chloroquine or hydroxychloroquine increase cleaved active SP-domain of TMPRSS2 HGNC, and this is potentiated by MEKi. In some human cells, remdesivir increases ACE2 HGNC-promoter luciferase-reporter expression, ACE2 HGNC mRNA and protein, and ACE2 HGNC expression is attenuated by MEKi. We show elevated cytokines in COVID-19 MESHD- (+) patient plasma (N=9) versus control (N=11). TMPRSS2 HGNC, inflammatory cytokines G-CSF HGNC, M- CSF HGNC, IL-1a HGNC, IL-6 HGNC and MCP-1 HGNC are suppressed by MEKi alone or in combination with remdesivir. MEKi enhance NK cell (but not T-cell) killing of target-cells, without suppressing TRAIL HGNC-mediated cytotoxicity MESHD. We generated a pseudotyped SARS-CoV-2 virus with a lentiviral core but with the SARS-CoV-2 D614 or G614 SPIKE (S) protein PROTEIN on its envelope and used VSV-G lentivirus as a negative control. Our results show infection of human bronchial epithelial cells or lung cancer MESHD cells and that MEKi suppress infectivity of the SARS-CoV-2-S pseudovirus following infection MESHD. We show a drug class-effect with MEKi to promote immune responses involving NK cells, inhibit inflammatory cytokines and block host-factors for SARS-CoV-2 infection MESHD leading also to suppression of SARS-CoV-2-S pseudovirus infection MESHD of human cells in a model system. MEKi may attenuate coronavirus infection MESHD to allow immune responses and antiviral agents to control COVID-19 MESHD disease progression and severity.

    TMPRSS2 HGNC, a SARS-CoV-2 internalization protease is downregulated in head and neck cancer patients.

    Authors: Andrea Sacconi; Sara Donzelli; Claudio Pulito; Stefano Ferrero; Aldo Morrone; Marta Rigoni; Fulvia Pimipinelli; Fabrizio Ensoli; Giuseppe Sanguineti; Raul Pellini; Nishant Agrawal; Evgeny Izumchenko; Gennaro Ciliberto; Aldo Gianni; Paola Muti; Sabrina Strano; Giovanni Blandino

    doi:10.1101/2020.06.16.154211 Date: 2020-06-16 Source: bioRxiv

    ObjectivesTwo of the main target tissues of SARS-coronavirus MESHD 2 are the oral cavity pharynx-larynx epithelium, the main virus entry site, and the lung epithelium. The virus enters host cells through binding of the Spike protein PROTEIN to ACE2 HGNC receptor and subsequent S priming by the TMPRSS2 HGNC protease. Herein we aim to assess differences in both ACE2 HGNC and TMPRSS2 HGNC expression in normal tissues from oral cavity-pharynx-larynx and lung tissues as well as neoplastic tissues from the same histological areas. The information provided in this study may contribute to better understanding of SARS-coronavirus MESHD 2 ability to interact with different biological systems and contributes to cumulative knowledge on potential mechanisms to inhibit its diffusion. Materials and MethodsThe study has been conducted using The Cancer Genome Atlas (TCGA) and the Regina Elena Institute (IRE) databases and validated by experimental model in HNSCC and Lung cancer cells. Data from one COVID19 MESHD positive patient who was operated on for HNSCC was also included. We have analyzed 478 tumor samples and 44 normal samples from TCGA HNSCC cohort for whom both miRNA and mRNA sequencing was available. The dataset included 391 HPV- and 85 HPV+ cases, with 331 P53 HGNC mutated and 147 P53 HGNC wild type cases respectively. 352 out of 478 samples were male and 126 female. In IRE cohort we analyzed 66 tumor samples with matched normal sample for miRNA profiling and 23 tumor\normal matched samples for mRNA profiling. 45 out of 66 tumors from IRE cohort were male and 21 female, 38 were P53 HGNC mutated and 27 wild type. Most patients (63 of 66) in IRE cohort were HPV negative. Normalized TCGA HNSCC gene expression and miRNA expression data were obtained from Broad Institute TCGA Genome Data Analysis Center ( mRNA expression data from IRE cohort used in this study has been deposited to NCBIs Gene Expression Omnibus and is accessible through GEO series accession number GSE107591. In order to inference about potential molecular modulation of TMPRSS2 HGNC, we also included miRNAs expression for the 66 IRE cohort matched tumor and normal samples from Agilent platform. DNA methylation data for TCGA tumors were obtained from Wanderer ( We used miRWalk and miRNet web tools for miRNA-target interaction prediction and pathway enrichment analysis. The correlation and regression analyses as well as the miRNA and gene modulation and the survival analysis were conducted using Matlab R2019. ResultsTMPRSS2 expression in HNSCC was significantly reduced compared to the normal tissues and had a prognostic value in HNSCC patients. Reduction of TMPRSS2 HGNC expression was more evident in women than in men, in TP53 HGNC mutated versus wild TP53 HGNC tumors as well as in HPV negative patients compared to HPV positive counterparts. Functionally, we assessed the multivariate effect on TMPRSS2 HGNC in a single regression model. We observed that all variables had an independent effect on TMPRSS2 HGNC in HNSCC patients with HPV negative, TP53 HGNC mutated status and with elevated TP53 HGNC-dependent Myc HGNC-target genes associated with low TMPRSS2 HGNC expression. Investigation of the molecular modulation of TMPRSS2 HGNC in both HNSCC and lung cancers revealed that expression of microRNAs targeting TMPRSS2 HGNC anti-correlated in both TCGA and IRE HNSCC datasets, while there was not evidence of TMPRSS2 HGNC promoter methylation in both tumor cohorts. Interestingly, the anti-correlation between microRNAs and TMPRSS2 HGNC expression was corroborated by testing this association in a SARS-CoV-2 positive HNSCC patient. ConclusionsCollectively, these findings suggest that tumoral tissues, herein exemplified by HNSCC and lung cancers might be more resistant to SARS-CoV-2 infection MESHD due to reduced expression of TMPRSS2 HGNC. The protective mechanism might occur, at least partially, through the aberrant activation of TMPRSS2 HGNC targeting microRNAs; thereby providing strong evidence on the role of non-coding RNA molecule in host viral infection. These observations may help to better assess the frailty of SARS-CoV-2 positive cancer patients.

    Single Amino Acid Variant (SAV) Percentage and Monomer Modeling of Spike Protein PROTEIN of SARS-CoV-2 in Jordan

    Authors: Walid Al-Zyoud; Hazem Haddad; Ramzi Foudeh

    id:10.20944/preprints202006.0184.v1 Date: 2020-06-14 Source:

    Spike protein PROTEIN is the surface glycoprotein of the severe acute respiratory syndrome-coronavirus-2 MESHD (SARS-CoV-2) necessary for the entry of the virus via the transmembrane receptors of the human endothelial cells of the respiratoty system for the virus to be engulfed causing COVID-19 MESHD disease after priming by type II transmembrane protease TMPRSS2 HGNC and then binding with the angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC). Therefore, mutations and amino acid variants analysis are essential in understanding the mechanism of binding of spike protein PROTEIN with its receptor to have an insights on possibilities to design a peptide or nucleotide-based vaccine for COVID-19 MESHD. Here, we employed Iterative Threading Assembly Refinement (I-TASSER) and Multiple Alignment using Fast Fourier Transform (MAFFT) to predict the three-dimensional monomer structure of spike protein PROTEIN of SARS-CoV-2 and to analyze the amino acid variants for protein sequences from GISAID database for samples collected from Jordan in a try to find an explanation for the low confirmed number of COVID-19 MESHD in Jordan. Our Protein Homology/analogY Recognition Engine V 2.0 (Phyre2) findings showed four single amino acid variants ( SAV MESHD) found in 20 samples of SARS-CoV-2. What is equal to 5% of samples showed tyrosine deletion at Y144 located in the SARS-CoV-like_Spike_S1_NTD (N terminal domain), 62% showed aspartate substitution to glycine at D614G located in the SARS-CoV-2_Spike_S1_RBD (spike recognition binding site), 5% showed aspartate substitution to tyrosine at D1139Y and 5% showed glycine substitution to serine at G1167S both located in the Corona_S2 domain. The findings have shown lower mutational sensitivity in all variants that might not affect the function of spike glycoprotein PROTEIN except for D614G, which has the highest mutational sensitivity score (5 out of 9) indicating a higher likelihood to affect the function of the spike protein PROTEIN. This might suggest, in general, a reduced transmitability of SARS-CoV-2 in Jordan.

    Spike protein PROTEIN modeling and single amino acid variant analysis might suggest reduced transmitability of SARS-CoV-2 in Jordan, Middle East

    Authors: Walid Al-Zyoud; Hazem Haddad; Ramzi Foudeh

    doi:10.21203/ Date: 2020-06-02 Source: ResearchSquare

    Spike protein PROTEIN (approx. 180 kDa) is the surface glycoprotein of the severe acute respiratory syndrome-coronavirus-2 MESHD (SARS-CoV-2) necessary for the interaction of the virus with human endothelial cell receptors on the cell membrane to be engulfed causing COVID-19 MESHD disease after binding with the angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC) with an evident activation by type II transmembrane protease TMPRSS2 HGNC . Therefore, mutations and amino acid variants analysis are essential in characterizing the mechanism of binding of spike protein PROTEIN with its receptor, which totally gives insights on possibilities to design a peptide or nucleotide-based vaccine for COVID-19 MESHD. Here, we employed Iterative Threading Assembly Refinement (I-TASSER) and Multiple Alignment using Fast Fourier Transform (MAFFT) to predict the three-dimensional structure and to analyze the amino acid variants for spike protein PROTEIN sequences of SARS-CoV-2 from GISAID database of samples collected from Jordan to try to find a justification for low number of confirmed COVID-19 MESHD in Jordan, Middle East. Our findings showed the molecules structurally close to the spike glycoprotein PROTEIN from the Enzyme Commission (EC) numbers and active sites included Isoleucyl-tRNA synthetase HGNC, Crystal structure of the tricorn protease (hydrolase); Crystal structure of the T. Thermophilus RNA polymerase holoenzyme (transferase); Crystal structure of the complex between pyruvate-ferredoxin oxidoreductase from Desulfovibrio africanus and pyruvate (oxidoreductase); and Reovirus core (virus). Our MAFFT findings showed that Four Amino Acid Variants (SAV) founded in 20 samples of SARS-CoV-2 were not conserved residues in spike glycoprotein PROTEIN. What is equal to 5% of samples showed tyrosine (polar) deletion at Y144 , 62% of samples showed aspartate (polar, acidic) substitution to glycine (nonpolar) at D614G, 5% of samples showed aspartate (polar, acidic) substitution to tyrosine (polar) at D1139Y and 5% of samples showed glycine (nonpolar) substitution to serine (polar) at G1167S respectively. By using Phyre2, our findings have shown lower sensitive mutational that cannot affect the pocket region or alpha and beta-sheet in all mutations except for D614G, which has the highest mutational sensitivity score (5 out of 9) indicating a bigger effect on the function of spike protein PROTEIN. This might suggest, in general, a reduced transmitability of SARS-CoV-2 in Jordan, Middle East. As the crystal structure of spike protein PROTEIN is not revealed yet, it was not possible to compare the predicted modes versus each other.

    Transcriptional profiling reveals TRPM5 HGNC-expressing cells involved in viral infection in the olfactory epithelium

    Authors: Eric D Larson; Paul Feinstein; Arianna Gentile Polese; Andrew N Bubak; Christy S Niemeyer; Laetitia Merle; Douglas Shepherd; Vijay R Ramakrishnan; Maria A Nagel; Diego Restrepo

    doi:10.1101/2020.05.14.096016 Date: 2020-05-15 Source: bioRxiv

    BackgroundUnderstanding viral infection of the olfactory epithelium is essential because smell loss can occur with coronavirus disease 2019 MESHD ( COVID-19 MESHD), caused by severe acute respiratory syndrome coronavirus clade MESHD 2 (SARS-CoV-2), and because the olfactory nerve is an important route of entry for viruses to the central nervous system. Specialized chemosensory epithelial cells that express the transient receptor potential cation channel subfamily M member 5 HGNC (TRPM5) are found throughout the airways and intestinal epithelium and are involved in responses to viral infection MESHD. ResultsHerein we performed deep transcriptional profiling of olfactory epithelial cells sorted by flow cytometry based on the expression of fluorescent protein markers for olfactory sensory neurons and TRPM5 in the mouse (Mus musculus). We find profuse expression of transcripts involved in inflammation, immunity and viral infection in TRPM5-expressing microvillous cells and olfactory sensory neurons. These cells express the Tmprss2 HGNC transcript that encodes for a serine protease that primes the SARS-CoV-2 spike PROTEIN protein before entry into host cells. Intranasal infection with herpes simplex virus type 1 (HSV-1) elicited a decrease in olfactory sensory neurons. ConclusionOur study provides new insights into a potential role for TRPM5-expressing cells in viral infection of the olfactory epithelium. We find that, as found for solitary chemosensory cells (SCCs) and brush cells in the airway epithelium, and for tuft cells in the intestine, the transcriptome of TRPM5-expressing microvillous cells and olfactory sensory neurons indicates that they are likely involved in the inflammatory response elicited by viral infection of the olfactory epithelium.

    Single-Cell RNA-seq Identifies Cell Subsets in Human Placenta That Highly Expresses Factors to Drive Pathogenesis of SARS-CoV-2

    Authors: Nancy Ashray; Anshul Bhide; Priyanka Chakarborty; Stacy Colaco; Anuradha Mishra; Karisma Chhabria; Mohit Kumar Jolly; Deepak Modi

    id:10.20944/preprints202005.0195.v1 Date: 2020-05-11 Source:

    Infection by the Severe Acute Respiratory Syndrome-Coronavirus-2 MESHD (SARS-CoV-2) results in the novel coronavirus disease COVID-19 MESHD, which has posed a serious threat globally. Infection of SARS-CoV-2 during pregnancy is associated with complications like preterm labor MESHD and premature rupture of membranes; a proportion of neonates born to the infected mothers are also positive for the virus. During pregnancy, the placental barrier protects the fetus from pathogens and ensures healthy development. However, whether or not SARS-CoV-2 can infect MESHD the placenta is unknown. Herein, utilizing single-cell RNA-seq data, we report that the SARS-CoV-2 binding receptor A CE2 HGNCand the S protein PROTEIN priming protease T MPRSS2 HGNCare co-expressed by a subset of syncytiotrophoblasts (STB) in the first trimester and extra villous trophoblasts (EVT) in the second trimester human placenta. The A CE2- HGNC and T MPRSS2- HGNCpositive (A CE2+ HGNCT MPRSS2+ HGNC) placental subsets express mRNA for proteins involved in viral budding and replication. These cells also express mRNA for proteins that interact with SARS-CoV-2 structural and non-structural proteins in the host cells. We also discovered unique signatures of genes in A CE2+ HGNCT MPRSS2+ HGNC STBs and EVTs. The A CE2+ HGNCT MPRSS2+ HGNC STBs are highly differentiated cells and express genes involved mitochondrial metabolism and glucose transport. The second trimester A CE2+ HGNCT MPRSS2+ HGNC EVTs are enriched for markers of endovascular trophoblasts. Further, both these subtypes abundantly expressed genes in Toll like receptor pathway, the second trimester EVTs (but not first trimester STBs) are also enriched for component of the JAK-STAT pathway that drive inflammation MESHD. To conclude, herein we uncovered the cellular targets for SARS-CoV-2 entry MESHD and show that these cells can potentially drive viremia MESHD in the developing human placenta. Our results provide a basic framework towards understanding the paraphernalia involved in SARS-CoV-2 infections MESHD in pregnancy.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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