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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (99)

ProteinN (5)

ProteinE (3)

NSP5 (2)

ComplexRdRp (1)


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SARS-CoV-2 Proteins
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    Common dandelion (Taraxacum officinale) efficiently blocks the interaction between ACE2 cell surface receptor and SARS-CoV-2 spike PROTEIN protein D614, mutants D614G, N501Y, K417N and E484K in vitro

    Authors: Hoai Thi Thu Tran; Nguyen Phan Khoi Le; Michael Gigl; Corinna Dawid; Evelyn Lamy

    doi:10.1101/2021.03.19.435959 Date: 2021-03-19 Source: bioRxiv

    On 11th March 2020, coronavirus disease 2019 MESHD ( COVID-19 MESHD), caused by the SARS-CoV-2 virus, was declared as a global pandemic by the World Health Organization (WHO). To date, there are rapidly spreading new "variants of concern" of SARS-CoV-2, the United Kingdom (B.1.1.7), the South African (B.1.351) or Brasilian (P.1) variant. All of them contain multiple mutations in the ACE2 HGNC receptor recognition site of the spike protein PROTEIN, compared to the original Wuhan sequence, which is of great concern, because of their potential for immune escape. Here we report on the efficacy of dandelion (Taraxacum officinale) to block protein-protein interaction of spike S1 to the human ACE2 cell surface receptor. This could be shown for the original spike D614, but also for its mutant forms (D614G, N501Y, and mix of K417N, E484K, N501Y) in human HEK293- hACE2 HGNC kidney and A549- hACE2 HGNC- TMPRSS2 HGNC lung cells. High molecular weight compounds in the water-based extract account for this effect. Infection of lung cells using SARS-CoV-2 spike PROTEIN pseudotyped lentivirus particles was efficiently prevented by the extract and so was virus-triggered pro-inflammatory interleukin 6 secretion. Modern herbal monographs consider the usage of this medicinal plant as safe. Thus, the in vitro results reported here should encourage further research on the clinical relevance and applicability of the extract as prevention strategy for SARS-CoV-2 infection MESHD.

    Replication kinetic, cell tropism and associated immune responses in SARS-CoV-2 and H5N1 virus infected human iPSC derived neural models

    Authors: Lisa Bauer; Bas Lendemeijer; Lonneke Leijten; Carmen W. E. Embregts; Barry Rockx; Steven Aaron Kushner; Femke M.S. de Vrij; Debby van Riel

    doi:10.1101/2021.03.15.435472 Date: 2021-03-16 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection MESHD is associated with a wide variety of neurological complications MESHD. Even though SARS-CoV-2 is rarely detected in the central nervous system (CNS) or cerebrospinal fluid, evidence is accumulating that SARS-CoV-2 might enter the CNS via the olfactory nerve. However, what happens after SARS-CoV-2 enters the CNS is poorly understood. Therefore, we investigated the replication kinetics, cell tropism, and associated immune responses of SARS-CoV-2 infection MESHD in different types of neural cultures derived from human induced pluripotent stem cells (hiPSCs). SARS-CoV-2 was compared to the neurotropic and highly pathogenic H5N1 influenza A virus. SARS-CoV-2 infected MESHD a minority of individual mature neurons, without subsequent virus replication and spread, despite ACE2 HGNC, TMPRSS2 HGNC and NPR1 HGNC expression in all cultures. However, this sparse infection did result in the production of type-III-interferons and IL-8 HGNC. In contrast, H5N1 virus replicated and spread very efficiently in all cell types in all cultures. Taken together, our findings support the hypothesis that neurological complications might result from local immune responses triggered by virus invasion, rather than abundant SARS-CoV-2 replication in the CNS.

    Clomipramine suppresses ACE2 HGNC-mediated SARS-CoV-2 entry MESHD

    Authors: Yuri Kato; Shigeru Yamada; Kazuhiro Nishiyama; Ayano Satsuka; Suyong Re; Daiki Tomokiyo; Jae Man Lee; Tomohiro Tanaka; Akiyuki Nishimura; Kenzo Yonemitsu; Hiroshi Asakura; Yuko Ibuki; Yumiko Imai; Noriho Kamiya; Kenji Mizuguchi; Takahiro Kusakabe; Yasunari Kanda; Motohiro Nishida

    doi:10.1101/2021.03.13.435221 Date: 2021-03-14 Source: bioRxiv

    Myocardial damage caused by the newly emerged coronavirus ( SARS-CoV-2) infection MESHD is one of key determinants of COVID-19 MESHD severity and mortality. SARS-CoV-2 entry to host cells are initiated by binding with its receptor, angiotensin converting enzyme (ACE) 2 HGNC, and the ACE2 HGNC abundance is thought to reflect the susceptibility to infection. Here, we found that clomipramine, a tricyclic antidepressant, potently inhibits SARS-CoV-2 infection MESHD and metabolic disorder MESHD in human iPS-derived cardiomyocytes. Among 13 approved drugs that we have previously identified as potential inhibitor of doxorubicin-induced cardiotoxicity MESHD, clomipramine showed the best potency to inhibit SARS-CoV-2 spike PROTEIN glycoprotein pseudovirus-stimulated ACE2 HGNC internalization. Indeed, SARS-CoV-2 infection MESHD to human iPS-derived cardiomyocytes (iPS-CMs) and TMPRSS2 HGNC-expressing VeroE6 cells were dramatically suppressed even after treatment with clomipramine. Furthermore, the combined use of clomipramine and remdesivir was revealed to synergistically suppress SARS-CoV-2 infection MESHD. Our results will provide the potentiality of clomipramine for the breakthrough treatment of severe COVID-19 MESHD.

    A simplified SARS-CoV-2 pseudovirus neutralization assay

    Authors: Gaetano Donofrio; Valentina Franceschi; Francesca Macchi; Luca Russo; Anna Rocci; Valentina Marchica; Federica Costa; Nicola Giuliani; Carlo Ferrari; Gabriele Missale

    doi:10.1101/2021.03.12.21253435 Date: 2021-03-12 Source: medRxiv

    COVID-19 MESHD is an ongoing pandemic caused by the highly infectious coronavirus SARS-CoV-2 that is engaging worldwide scientific research to find a timely and effective eradication strategy. Great efforts have been put into anti- COVID-19 MESHD vaccine generation in an effort to protect the world population and block SARS-CoV-2 spread. To validate the protective efficacy of the vaccination campaign and effectively control the pandemy, it is necessary to quantify the neutralizing antibodies induction by vaccination, since they have been established to be a correlate of protection. In this work a SARS-CoV-2 pseudovirus neutralization assay, based on a replication incompetent lentivirus expressing an adapted form of CoV-2 S protein PROTEIN and an ACE2 HGNC/ TMPRSS2 HGNC stably expressing cell line, have been minimized in term of protocol steps without loss of accuracy. The goal of the present simplified neutralization system is to improve SARS-CoV-2 vaccination campaign by means of an easy and accessible approach to be performed in any medical laboratory, maintaining the sensitivity and quantitative reliability of classical serum neutralization assays. Further this assay can be easily adapted to different coronaviruses variants by simply modifying the pseudotyping vector.

    A common TMPRSS2 HGNC variant protects against severe COVID-19 MESHD

    Authors: Alessia David; Nicholas Parkinson; Thomas P Peacock; Erola Pairo-Castineira; Tarun Khanna; Aurelie Cobat; Albert Tenesa; Vanessa Sancho-Shimizu; - GenOMICC Investigators, ISARIC4C Investigators; Jean-Laurent Casanova; Laurent Abel; Wendy S Barclay; J Kenneth Baillie; Michael J.E. Sternberg

    doi:10.1101/2021.03.04.21252931 Date: 2021-03-08 Source: medRxiv

    Infection with SARS-CoV-2 has a wide range of clinical presentations, from asymptomatic to life-threatening. Old age is the strongest factor associated with increased COVID19 MESHD-related mortality, followed by sex and pre-existing conditions. The importance of genetic and immunological factors on COVID19 MESHD outcome is also starting to emerge, as demonstrated by population studies and the discovery of damaging variants in genes controlling type I IFN immunity and of autoantibodies that neutralize type I IFNs. The human protein transmembrane protease serine type 2 ( TMPRSS2 HGNC) plays a key role in SARS-CoV-2 infection MESHD, as it is required to activate the virus spike protein PROTEIN, facilitating entry into target cells. We focused on the only common TMPRSS2 HGNC non-synonymous variant predicted to be damaging (rs12329760), which has a minor allele frequency of [~]25% in the population. In a large population of SARS-CoV-2 positive patients, we show that this variant is associated with a reduced likelihood of developing severe COVID19 MESHD (OR 0.87, 95%CI:0.79-0.97, p=0.01). This association was stronger in homozygous individuals when compared to the general population (OR 0.65, 95%CI:0.50-0.84, p=1.3x10-3). We demonstrate in vitro that this variant, which causes the amino acid substitution valine to methionine, impacts the catalytic activity of TMPRSS2 HGNC and is less able to support SARS-CoV-2 spike PROTEIN-mediated entry into cells. TMPRSS2 HGNC rs12329760 is a common variant associated with a significantly decreased risk of severe COVID19 MESHD. Further studies are needed to assess the expression of the TMPRSS2 HGNC across different age groups. Moreover, our results identify TMPRSS2 HGNC as a promising drug target, with a potential role for camostat mesilate, a drug approved for the treatment of chronic pancreatitis MESHD and postoperative reflux esophagitis MESHD, in the treatment of COVID19 MESHD. Clinical trials are needed to confirm this.

    Pediatric nasal epithelial cells are less permissive to SARS-CoV-2 replication compared to adult cells

    Authors: Yanshan Zhu; Keng Yih Chew; Anjana C. Karawita; Ayaho Yamamoto; Larisa L. Labzin; Tejasri Yarlagadda; Alexander A. Khromykh; Claudia J. Stocks; Yao Xia; Tobias R. Kollmann; David Martino; Anthony Kicic; Helle Bielefeldt-Ohmann; Asha C. Bowen; Peter D. Sly; Kirsten M. Spann; Kirsty R. Short

    doi:10.1101/2021.03.08.434300 Date: 2021-03-08 Source: bioRxiv

    Rationale: Young children (typically those <10 years old) are less susceptible to SARS-CoV-2 infection MESHD and symptoms compared to adults. However, the mechanisms that underlie these age-dependent differences remain to be determined and could inform future therapeutics for adults. Objective: To contrast the infection dynamics of SARS-CoV-2 in primary nasal epithelial cells from adults and children. Methods: Viral replication was quantified by plaque assay. The cellular transcriptome of infected and uninfected cells was assessed by RNA-seq. ACE2 HGNC and TMPRSS2 HGNC protein expression were quantified by Western Blot Measurements and Main Results: We report significantly higher SARS-CoV-2 replication in adult compared to pediatric nasal epithelial cells. This was restricted to SARS-CoV-2 infection MESHD, as the same phenomenon was not observed with influenza virus infection MESHD. The differentiational SARS-CoV-2 replication dynamics were associated with an elevated type I and III interferon response, and a more pronounced inflammatory response in pediatric cells. No significant difference between the two age groups was observed in the protein levels of ACE2 HGNC and TMPRSS2 HGNC. Conclusions: Our data suggest that the innate immune response of pediatric nasal epithelial cells, and not differential receptor expression, may contribute to the reported reduced SARS-COV-2 infection MESHD and symptoms reported amongst children.

    Bromhexine Hydrochloride Prophylaxis of COVID-19 MESHD for Medical Personnel: A Randomized Open-Label Study

    Authors: Evgeny N Mikhaylov; Tamara A Lyubimtseva; Aleksandr D Vakhrushev; Dmitry Stepanov; Dmitry S Lebedev; Elena Yu Vasilieva; Alexandra O Konradi; Evgeny V Shlyakhto

    doi:10.1101/2021.03.03.21252855 Date: 2021-03-08 Source: medRxiv

    BackgroundBromhexine hydrochloride has been suggested as a TMPRSS2 HGNC protease blocker that precludes the penetration of the SARS-CoV-2 into cells. We aimed to assess the preventive potential of regular bromhexine hydrochloride intake for COVID-19 MESHD risk reduction in medical staff actively involved in the evaluation and treatment of patients with confirmed or suspected SARS-CoV-2 infection MESHD. MethodsIn a single-center randomized open-label study medical staff managing patients with suspected and confirmed COVID-19 MESHD were enrolled and followed-up for 8 weeks. The study began at the initiation of COVID-19 MESHD management in the clinic. We enrolled 50 participants without a history of SARS-CoV-2 infection MESHD: 25 were assigned to bromhexine hydrochloride treatment (8 mg 3 times per day), and 25 were controls. The composite primary endpoint was a positive nasopharyngeal swab polymerase chain reaction (PCR) test to SARS-CoV-2 or the signs of clinical infection within 28 days and at week 8. Secondary endpoints included the symptomatic infection rate and positive nasopharyngeal swab (PCR) tests. ResultsThe rate of the combined primary endpoint did not differ significantly between the active treatment group (2/25 [8%]) and control group (7/25 [28%]); P = 0.07. A fewer number of participants developed symptomatic infection (confirmed COVID-19 MESHD) in the treatment group compared to controls (0/25 vs 5/25; P = 0.02). ConclusionBromhexine hydrochloride prophylaxis was associated with a reduced rate of symptomatic COVID-19 MESHD. However, the prophylactic treatment was not associated with a lower combined primary endpoint rate, a positive swab PCR test and/or COVID-19 MESHD. (ClinicalTrials.gov number, NCT04405999)

    Initial Study on TMPRSS2 HGNC p.Val160Met Genetic Variant in COVID-19 MESHD patients

    Authors: Laksmi Wulandari; Berliana Hamidah; Cennikon Pakpahan; Nevy Shinta Damayanti; Neneng Dewi Kurniati; Christophorus Oetama Adiatmaja; Monica Rizky Wigianita; Soedarsono Soedarsono; Dominicus Husada; Damayanti Tinduh; Cita Rosita Sigit Prakoeswa; Anang Endaryanto; Ni Nyoman Tri Puspaningsih; Maria Inge Lusida; Kazufumi Shimizu; Delvac Oceandy

    doi:10.21203/rs.3.rs-292930/v1 Date: 2021-03-03 Source: ResearchSquare

    Background Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is a global health problem that causes millions of deaths worldwide. The clinical manifestation of COVID-19 MESHD widely varies from asymptomatic infection to severe pneumonia MESHD and systemic inflammatory disease MESHD. It is thought that host genetic variability may affect the host's response to the virus infection MESHD and thus cause severity of the disease. The SARS-CoV-2 virus requires interaction with its receptor complex in the host cells before infection. The transmembrane protease serine 2 HGNC ( TMPRSS2 HGNC) has been identified as one of the key molecules involved in SARS-CoV-2 virus receptor binding and cell invasion. Therefore, in this study we investigated the correlation between a genetic variant within the human TMPRSS2 HGNC gene and COVID-19 MESHD severity and viral load.ResultsWe genotyped 95 patients with COVID-19 MESHD hospitalized in Dr Soetomo General Hospital and Indrapura Field Hospital (Surabaya, Indonesia) for the TMPRSS2 p HGNC.Val160Met polymorphism. Polymorphism was detected using a TaqMan assay. We then analysed the association between the presence of the genetic variant and disease severity and viral load. We did not observe any correlation between the presence of TMPRSS2 HGNC genetic variant with the severity of the disease. However, we identified significant association between the p.Val160Met polymorphism and the SARS-CoV-2 viral load, as estimated by the Ct value of the diagnostic nucleic acid amplification test. Furthermore, we observed a trend of association between the presence of the C allele and the mortality rate in patients with severe COVID-19 MESHD. ConclusionOur data indicate a possible association between TMPRSS2 HGNC p.Val160Met polymorphism and SARS-CoV-2 infectivity MESHD and the outcome of Covid-19 MESHD

    Human Blastocyst is Susceptible to SARS-CoV-2 Infection MESHD based on Protein Level Examination of Key Entry Factors in Human Oocytes and Early Embryos

    Authors: xingping liu; Bing-xin Ma; Li-quan Zhou

    doi:10.21203/rs.3.rs-288745/v1 Date: 2021-03-01 Source: ResearchSquare

    Objective ACE2 HGNC, TMPRSS2 HGNC and NRP1 HGNC are key factors for SARS-CoV-2 infection MESHD. Here, we used immunofluorescence to examine the expression patterns of ACE2 HGNC, TMPRSS2 HGNC and NRP1 HGNC in human oocytes and different stages of preimplantation embryos to investigated the susceptibility to be infected MESHD by SARS-CoV-2.Methods We collected human GV oocytes and different stages of early embryos donated by patients and then performed immunofluorescence followed by confocal microscopy for signals of ACE2 HGNC, TMPRSS2 HGNC and NRP1 HGNC proteins in these oocytes and embryos.Results We found that ACE2 HGNC was abundant in both inner cell mass and trophectoderm at blastocyst stage, while TMPRSS2 HGNC was mainly enriched in trophectoderm. Both of the two factors had faint signal in cleavage embryos and oocytes. In contrast, NRP1 HGNC was barely detectable in oocytes or any stage of early embryos. Conclusion Taken together, we propose that human blastocysts, instead of human oocytes and other stages of early embryos, are susceptible to be infected by SARS-CoV-2. Therefore, specific attention should be paid to manipulation of human blastocysts in assisted reproductive technology.

    Comprehensive evaluation of ACE2 HGNC expression in female ovary by single-cell RNA-seq analysis

    Authors: Siming Kong; Zhiqiang Yan; Peng Yuan; Xixi Liu; Yidong Chen; Ming Yang; Wei Chen; Shi Song; Jie Yan; Liying Yan; Jie Qiao

    doi:10.1101/2021.02.23.432460 Date: 2021-02-23 Source: bioRxiv

    Pneumonia induced by severe acute respiratory coronavirus MESHD 2 (SARS-CoV-2) via ACE2 HGNC receptor may affect many organ systems like lung, heart and kidney. An autopsy report revealed positive SARS-Cov-2 detection results in ovary MESHD, however, the developmental-stage-specific and cell-type-specific risk in fetal primordial germ cells (PGCs) and adult women ovary remained unclear. In this study, we used single-cell RNA-sequencing (scRNA-seq) datasets spanning several developmental stages of ovary MESHD including PGCs and cumulus-oocyte complex (COC) to investigate the potential risk of SARS-CoV-2 infection MESHD. We found that PGCs and COC exhibited high ACE2 HGNC expression. More importantly, the ratio of ACE2 HGNC-positive cells was sharply up-regulated in primary stage and ACE2 HGNC was expressed in all oocytes and cumulus cells in preovulatory stage, suggesting the possible risk of SARS-CoV-2 infection MESHD in follicular development. CatB HGNC/L, not TMPRSS2 HGNC, was identified to prime for SARS-CoV-2 entry MESHD in follicle. Our findings provided insights into the potential risk of SARS-CoV-2 infection MESHD during folliculogenesis in adulthood and the possible risk in fetal PGCs.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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