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    Evaluation of vertical transmission of SARS-CoV-2 in utero: nine pregnant women and their newborns

    Authors: Liang Dong; Shiyao Pei; Qin Ren; Shuxiang Fu; Liang Yu; Hui Chen; Xiang Chen; Mingzhu Yin

    doi:10.1101/2020.12.28.20248874 Date: 2021-01-08 Source: medRxiv

    BackgroundSevere acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), mainly transmitted by droplets and close contact, has caused a pandemic worldwide as of November 2020. According to the current case reports and cohort studies, the symptoms of pregnant women infected with SARS-CoV-2 were similar to normal adults and may cause a series of adverse consequences of pregnancy (placental abruption, fetal distress, epilepsy MESHD during pregnancy, etc.). However, whether SARS-CoV-2 can be transmitted to the fetus through the placental barrier is still a focus of debate. MethodsIn this study, in order to find out whether SARS-CoV-2 infect MESHD fetus through placental barrier, we performed qualitative detection of virus structural protein (spike PROTEIN protein and nucleoprotein PROTEIN) and targeted receptor protein ( ACE2 HGNC, CD147 HGNC and GRP78 HGNC) expression on the placental tissue of seven pregnant women diagnosed with COVID-19 MESHD through immunohistochemistry. Amniotic fluid, neonatal throat, anal swab and breastmilk samples were collected immediately in the operating room for verification after delivery, which were all tested for SARS-CoV-2 by reverse transcriptionpolymerase chain reaction (RT-PCR). Results: The result showed that CD147 HGNC was expressed on the basal side of the chorionic trophoblast cell membrane and ACE2 HGNC was expressed on the maternal side, while GRP78 HGNC was strongly expressed in the cell membrane and cytoplasm. The RT-PCR results of Amniotic fluid, neonatal throat, anal swab and breastmilk samples were all negative. Conclusions: We believed that despite the detection of viral structural proteins in the placenta, SARS-CoV-2 cannot be transmitted to infants due to the presence of the placental barrier.

    Paradoxical effects of cigarette smoke and COPD MESHD on SARS-CoV2 infection MESHD and disease

    Authors: Michael Tomchaney; Marco Contoli; Jonathan Mayo; Simonetta Baraldo; Shuaizhi Li; Carly Cabel; David Bull; Scott Lick; Joshua Malo; Steve Knoper; Samuel Kim; Judy Tram; Joselyn Rojas Quintero; Monica Kraft; Julie Ledford; Fernando D Martinez; Curtis Thorne; Farrah Kheradmand; Samuel K Campos; Alberto Papi; Francesca Polverino

    doi:10.1101/2020.12.07.413252 Date: 2020-12-07 Source: bioRxiv

    IntroductionHow cigarette smoke (CS) and chronic obstructive pulmonary disease MESHD ( COPD MESHD) affect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD and severity is controversial. We investigated the protein and mRNA expression of SARS-CoV-2 entry receptor ACE2 HGNC and proteinase TMPRSS2 HGNC in lungs from COPD MESHD patients and controls, and lung tissue from mice exposed acutely and chronically to CS. Also, we investigated the effects of CS exposure on SARS-CoV-2 infection MESHD in human bronchial epithelial cells. MethodsIn Cohort 1, ACE2 HGNC-positive cells were quantified by immunostaining in FFPE sections from both central and peripheral airways. In Cohort 2, we quantified pulmonary ACE2 HGNC protein levels by immunostaining and ELISA, and both ACE2 HGNC and TMPRSS2 HGNC mRNA levels by RT-qPCR. In C57BL/6 WT mice exposed to air or CS for up to 6 months, pulmonary ACE2 protein levels were quantified by triple immunofluorescence staining and ELISA. The effects of CS exposure on SARS-CoV-2 infection MESHD were evaluated after 72hr in vitro infection of Calu-3 cells. After SARS-CoV-2 infection MESHD, the cells were fixed for IF staining with dsRNA-specific J2 monoclonal Ab, and cell lysates were harvested for WB of viral nucleocapsid (N) protein PROTEIN. Supernatants (SN) and cytoplasmic lysates were obtained to measure ACE2 HGNC levels by ELISA. ResultsIn both human cohorts, ACE2 HGNC protein and mRNA levels were decreased in peripheral airways from COPD MESHD patients versus both smoker and NS controls, but similar in central airways. TMPRSS2 HGNC levels were similar across groups. Mice exposed to CS had decreased ACE2 protein levels in their bronchial and alveolar epithelia MESHD versus air-exposed mice exposed to 3 and 6 months of CS. In Calu3 cells in vitro, CS-treatment abrogated infection to levels below the limit of detection. Similar results were seen with WB for viral N protein PROTEIN, showing peak viral protein synthesis at 72hr. ConclusionsACE2 levels were decreased in both bronchial and alveolar epithelial MESHD cells from uninfected COPD MESHD patients versus controls, and from CS-exposed versus air-exposed mice. CS-pre-treatment did not affect ACE2 levels but potently inhibited SARS-CoV-2 replication in this in vitro model. These findings urge to further investigate the controversial effects of CS and COPD MESHD on SARS-CoV2 infection MESHD.

    Rapid and accurate point-of-care testing for SARS-CoV2 antibodies

    Authors: Shawn SC Li; Sally Esmail; Michael Knauer; Husam Abdoh; Benjamin Chin-Yee; Lori Lowes; Courtney Voss; Benjamin Hedley; Vipin Bhayana; Ian Chin-Yee; Alma Seitova; Ashley Hutchinson; Farhad Yusifov; Tatiana Skarina; Elena Evdokimova; Suzanne Ackloo; Peter Stogios

    doi:10.1101/2020.11.30.20241208 Date: 2020-12-02 Source: medRxiv

    The COVID-19 MESHD COVID-19 MESHD pandemic, caused by the severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2), has grown into worst public health crisis since the 1918 influenza pandemic. As COVID-19 MESHD continues to spread around the world, there is urgent need for a rapid, yet accurate antibody test to identify infected individuals in populations to inform health decisions. We have developed a rapid, accurate and cost-effective serologic test based on antibody-dependent agglutination of antigen-coated latex particles, which uses ~5 ul plasma and takes <5 min to complete with no instrument required. The simplicity of this test makes it ideal for point-of-care (POC) use at the community level. When validated using plasma samples that are positive or negative for SARS-CoV-2, the agglutination assay detected antibodies against the receptor-binding domain of the spike (S-RBD) or the nucleocapsid (N) protein PROTEIN of SARS-CoV-2 with 100% specificity and ~98% sensitivity. Furthermore, we found that the strength of the S-RBD antibody response measured by the agglutination assay correlated with the efficiency of the plasma in blocking RBD binding to the angiotensin converting enzyme 2 HGNC ( ACE2 HGNC) in a surrogate neutralization assay, suggesting that the agglutination assay may be used to identify individuals with virus-neutralizing antibodies. Intriguingly, we found that >92% of patients had detectable antibodies on the day of positive viral RNA test, suggesting that seroconversion may occur earlier than previously thought and that the agglutination antibody test may complement RNA testing for POC diagnosis of SARS-CoV-2 infection MESHD.

    Discovery of Natural Phenol Catechin as a Multitargeted Agent Against SARS-CoV-2 For the Plausible Therapy of COVID-19 MESHD

    Authors: Chandra Bhushan Mishra; Preeti Pandey; Ravi Datta Sharma; Raj Kumar Mongre; Andrew M Lynn; Rajendra Prasad; Raok Jeon; Amresh Prakash

    doi:10.26434/chemrxiv.12752402.v1 Date: 2020-08-04 Source: ChemRxiv

    The global pandemic crisis, COVID-19 MESHD caused by severe acute respiratory syndrome coronavirus MESHD 2 (SARS-CoV-2) has claimed the lives of millions of people across the world. Development and testing of anti-SARS-CoV-2 drugs or vaccines, are not turned to be realistic in the timeframe needed to combat this pandemic. Thus, rigorous efforts are still ongoing for the drug repurposing as a clinical treatment strategy to control COVID-19 MESHD. Here we report a comprehensive computational approach to identify the multi-targeted drug molecules against the SARS-CoV-2 proteins, which are crucially involved in the viral-host interaction, replication of the virus inside the host, disease progression and transmission of coronavirus infection. Virtual screening of 72 FDA approved potential antiviral drugs against the target proteins: Spike (S PROTEIN) glycoprotein, human angiotensin-converting enzyme 2 ( hACE2 HGNC), 3-chymotrypsin- like cysteine protease PROTEIN ( 3CLpro PROTEIN), Cathepsin L HGNC, Nucleocapsid protein PROTEIN, RNA-dependent RNA polymerase PROTEIN ( RdRp PROTEIN) and nonstructural protein 6 ( NSP6 PROTEIN) resulted in the selection of seven drugs which preferentially binds to the target proteins. Further, the molecular interactions determined by MD simulation, free energy landscape and the binding free energy estimation, using MM-PBSA revealed that among 72 drug molecules, catechin (flavan-3-ol) can effectively bind to 3CLpro PROTEIN, Cathepsin L HGNC, RBD of S protein PROTEIN, NSP-6, and Nucleocapsid protein PROTEIN. It is more conveniently involved in key molecular interactions, showing binding free energy (ΔGbind) in the range of -5.09 kcal/mol ( Cathepsin L HGNC) to -26.09 kcal/mol ( NSP6 PROTEIN). At the binding pocket, catechin is majorly stabilized by the hydrophobic interactions, displays ΔEvdW values -7.59 to -37.39 kcal/mol. Thus, the structural insights of better binding affinity and favourable molecular interaction of catechin towards multiple target proteins, signifies that catechin can be potentially explored as a multitargeted agent in the rational design of effective therapies against COVID-19 MESHD.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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