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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (3)

ORF8 (1)


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SARS-CoV-2 Proteins
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    Single point mutations can potentially enhance infectivity of SARS-CoV-2 revealed by in silico affinity maturation and SPR HGNC assay

    Authors: Ting Xue; Weikun Wu; Ning Guo; Chengyong Wu; Jian Huang; Lipeng Lai; Hong Liu; Yalun Li; Tianyuan Wang; Yuxi Wang; Anders Sonnerborg; Yihai Cao; Mikael Bjornstedt; Attila Szakos; Vinod Scaria; Paolo Bonfanti; Cor H van der Leest; Nidhi Rohatgi; Lothar Wiese; Charles Edouard Luyt; Farrah Kheradmand; Ivan O Rosas; Fang Cai; Panteleimon Tsiamalos; Konstantinos Syrigos; George Chrysos; Thomas Nitsotolis; Haralampos Milionis; Garyphallia Poulakou; Evangelos Giamarellos-Bourboulis

    doi:10.1101/2020.12.24.424245 Date: 2020-12-26 Source: bioRxiv

    The RBD (receptor binding domain) of the SARS-CoV-2 virus S MESHD S (spike) protein PROTEIN mediates the viral cell attachment and serves as a promising target for therapeutics development. Mutations on the S-RBD may alter its affinity to cell receptor and affect the potency of vaccines and antibodies. Here we used an in-silico approach to predict how mutations on RBD affect its binding affinity to hACE2 HGNC (human angiotensin-converting enzyme2 HGNC). The effect of all single point mutations on the interface was predicted. SPR HGNC assay result shows that 6 out of 9 selected mutations can strengthen binding affinity. Our prediction has reasonable agreement with the previous deep mutational scan results and recently reported mutants. Our work demonstrated in silico method as a powerful tool to forecast more powerful virus mutants, which will significantly benefit for the development of broadly neutralizing vaccine and antibody.

    LL-37 HGNC fights SARS-CoV-2: The Vitamin D-Inducible Peptide LL-37 HGNC Inhibits Binding of SARS-CoV-2 Spike PROTEIN Protein to its Cellular Receptor Angiotensin Converting Enzyme 2 HGNC In Vitro

    Authors: Annika Roth; Steffen Luetke; Denise Meinberger; Gabriele Hermes; Gerhard Sengle; Manuel Koch; Thomas Streichert; Andreas R. Klatt; Maarja Andaloussi Mae; Lars Muhl; Nicky M. Craig; Samantha J. Griffiths; Jurgen G. Haas; Christine Tait Burkard; Urban Lendahl; Graeme M. Birdsey; Christer Betsholtz; Michela Noseda; Andrew Baker; Anna M Randi; Sofia Palma; Carolina Escobar; Josefina bascunan; Rodrigo Munoz; Monica Pinto; Daniela Cardemil; Marcelo Navarrete; Soledad Reyes; Victoria Espinoza; Nicolas Yanez; Christian Caglevic

    doi:10.1101/2020.12.02.408153 Date: 2020-12-02 Source: bioRxiv

    Objective: Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is the pathogen accountable for the coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic. Viral entry via binding of the receptor binding domain (RBD) located within the S1 subunit of the SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN ( S) protein PROTEIN to its target receptor angiotensin converting enzyme (ACE) 2 HGNC is a key step in cell infection. The efficient transition of the virus is linked to a unique protein called open reading frame ( ORF MESHD) 8. As SARS-CoV-2 infection MESHD SARS-CoV-2 infection MESHDs can develop into life threatening lower respiratory syndromes, effective therapy options are urgently needed. Several publications propose vitamin D treatment, although its mode of action against COVID-19 MESHD is not fully elucidated. It is speculated that vitamin D's beneficial effects are mediated by up regulating LL-37 HGNC, a well known antimicrobial peptide with antiviral effects. Methods: Recombinantly expressed SARS-CoV-2 S protein PROTEIN, the extended S1 subunit (S1e), the S2 subunit (S2), the receptor binding domain (RBD), and ORF8 PROTEIN were used for surface plasmon resonance ( SPR HGNC) studies to investigate LL-37 HGNC's ability to bind to SARS-CoV-2 proteins MESHD and to localize its binding site within the S protein PROTEIN. Binding competition studies were conducted to confirm an inhibitory action of LL-37 HGNC on the attachment of SARS-CoV-2 S MESHD S protein PROTEIN to its entry receptor ACE2 HGNC. Results: We could show that LL-37 HGNC binds to SARS-CoV-2 S MESHD S protein PROTEIN ( LL-37 HGNC/S-Strep KD = 407 nM, LL-37 HGNC/S-His KD = 414 nM) with the same affinity, as SARS-CoV-2 binds to hACE2 HGNC ( hACE2 HGNC/S-Strep KD = 374 nM, hACE2 HGNC/S-His KD = 368 nM). The binding is not restricted to the RBD of the S protein PROTEIN, but rather distributed along the entire length of the protein. Interaction between LL-37 HGNC and ORF8 PROTEIN was detected with a KD of 294 nM. Further, inhibition of the binding of S-Strep (IC50 = 735 nM), S1e (IC50 = 168 nM), and RBD (IC50 = 126 nM) to hACE2 HGNC by LL-37 HGNC was demonstrated. Conclusions: We have revealed a biochemical link between vitamin D, LL-37 HGNC, and COVID-19 MESHD severity. SPR HGNC analysis demonstrated that LL-37 HGNC binds to SARS-CoV-2 S MESHD S protein PROTEIN and inhibits binding to its receptor hACE2 HGNC, and most likely viral entry into the cell. This study supports the prophylactic use of vitamin D to induce LL-37 HGNC that protects from SARS-CoV-2 infection MESHD, and the therapeutic administration of vitamin D for the treatment of COVID-19 MESHD patients. Further, our results provide evidence that the direct use of LL-37 HGNC by inhalation and systemic application may reduce the severity of COVID-19 MESHD.

    sMAdCAM:IL-6 (sMIL Index): A novel signature associated with COVID-19 MESHD disease progression and development of anti-SARS-CoV-2 antibodies

    Authors: Dhanashree Jagtap; Vikrant M Bhor; Shilpa Bhowmick; Nandini Kasarpalkar; Pooja Sagvekar; Bhalchandra Kulkarni; Manish Pathak; Nirjhar Chatterjee; Pranam Dolas; Harsha Palav; Snehal Kaginkar; Sharad Bhagat; Itti Munshi; Swapneil Parikh; Sachee Agrawal; Chandrakant Pawar; Mala Kaneria; Smita Mahale; Jayanthi Shastri; Vainav Patel

    doi:10.1101/2020.10.13.20182949 Date: 2020-10-16 Source: medRxiv

    IMPORTANCE: Recent studies positing the gut as a sanctuary site for viral persistence in SARS-CoV-2 infection MESHD highlight the importance of assimilating profiles of systemic as well as gut inflammatory mediators to understand the pathology of COVID-19 MESHD. Also, the role of these markers in governing virus specific immunity following infection remains largely unexplored. OBJECTIVE: To evaluate the role of systemic and gut inflammatory markers in disease progression and development of anti-viral humoral immunity following SARS-CoV-2 infection MESHD. DESIGN, SETTING AND PARTICIPANTS: This cohort study (n=58) of SARS-CoV-2 infected MESHD individuals included a group of in-patients (n=36) at various stages of disease progression together with convalescent individuals (n=22) recruited between April and June 2020 (peak of the epidemic) from a tertiary care hospital in Mumbai, India. Follow-up of 11 in-patients at day 7 post diagnosis was carried out, resulting in a total of 47 in-patient samples. EXPOSURES: Diagnosis of SARS-CoV-2 infections MESHD was confirmed by reverse transcriptase-polymerase chain reaction-based testing of nasopharyngeal/oropharyngeal samples. MAIN OUTCOMES AND MEASURES: Primary outcomes were the measurement of inflammatory markers including Th1 HGNC/Th2/Th17 cytokines and levels of soluble mucosal addressin cell adhesion molecule (sMAdCAM) in plasma. Anti-viral humoral response was measured by rapid antibody test (IgG, IgM) and chemiluminescent immunoassay (CLIA) (IgG). Also antibodies binding to SARS-CoV-2 proteins were measured by surface plasmon resonance ( SPR HGNC). Secondary outcomes were correlation of the inflammatory signature with clinical information, including age, sex, disease duration and co-morbidities. RESULTS: Twenty eight of 36 (78%) in-patients and 19 of 22 (86%) convalescents were males. Out of 47 in-patient samples, 22 (46%), 11 (23%) and 14 (30%) were IgG-/IgM-, IgG+/IgM+ and IgG+/IgM- respectively. Of 22 convalescent samples, 3 (14%), 1 (4%) and 17 (77%) were respectively IgG-/IgM-, IgG+/IgM+ and IgG+/IgM-. Two out of 22 (9%) convalescents showed high IL-6 HGNC levels (>100pg/ml) and 4 (18%) had high TNF HGNC levels (>30pg/ml). However, the convalescents (n =22) had significantly lower levels of IL-6 HGNC [Median=27.48 (IQR=23.54-39.92)] compared to followed up in-patients (n = 11) at day 0 [Median=111(IQR=68-129.7), p =0.0002] and higher levels of sMAdCAM [Median=1940 (1711-2174) pg/ml] compared to these individuals at day 0 [Median=1701 (IQR=1532-1836) pg/ml; p=0.032] and day 7 [Median=1534 (IQR=1236-1654) pg/ml; p=0.0007]. Further, IL-6 HGNC and sMAdCAM levels among in-patients inversely correlated with one another (r =-0.374, p = 0.009, CI = 95%). When expressed as a novel integrated marker, sMIL (sMAdCAM/ IL-6 HGNC ratio) index, these levels were incrementally and significantly higher across various disease states with convalescents exhibiting the highest values [Median= 64.74 (IQR=47.33-85.58)]. Also, the sMIL index was significantly higher in convalescents (with class-switched responses) compared to IgG+/IgM+ individuals at early stages of infection [Median=28.65 (IQR=13.63-96.26), p = 0.034]. Real-time measurement by SPR HGNC of plasma antibody binding to viral nucleocapsid (NC), receptor binding domain (RBD) and spike (S) revealed waxing and waning of plasma antibody responses to all 3 targets. Importantly, sMAdCAM levels as well as sMIL index (fold change) correlated with peak association rates of RBD-binding (r = 0.462, p = 0.03, CI = 95%) and fold change in binding to S (r = 0.68, p = 0.050, CI = 95%) respectively. CONCLUSION AND RELEVANCE: Our results highlight key systemic and gut-associated immune parameters that need to be monitored and investigated further to optimally guide therapeutic and prophylactic interventions for COVID-19 MESHD.

    Bromelain Inhibits SARS-CoV-2 Infection MESHD in VeroE6 Cells

    Authors: Satish Sagar; Ashok Kumar Rathinavel; 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:10.1101/2020.09.16.297366 Date: 2020-09-16 Source: bioRxiv

    Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is caused by severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2). The initial interaction between Transmembrane Serine Protease 2 (TMPRSS2) primed SARS-CoV-2 spike PROTEIN SARS-CoV-2 spike MESHD ( S) protein PROTEIN and host cell receptor angiotensin-converting enzyme 2 ( ACE-2 HGNC) is a pre-requisite step for this novel coronavirus pathogenesis. Here, we expressed a GFP-tagged SARS-CoV-2 S-Ectodomain in Tni insect cells. That contained sialic acid-enriched N- and O-glycans. Surface resonance plasmon ( SPR HGNC) and Luminex assay showed that the purified S-Ectodomain binding to human ACE-2 HGNC and immunoreactivity with COVID-19 MESHD positive samples. We demonstrate that bromelain (isolated from pineapple stem and used as a dietary supplement) treatment diminishes the expression of ACE-2 HGNC and TMPRSS2 in VeroE6 cells and dramatically lowers the expression of S-Ectodomain. Importantly, bromelain treatment reduced the interaction between S-Ectodomain and VeroE6 cells. Most importantly, bromelain treatment significantly diminished the SARS-CoV-2 infection MESHD in VeroE6 cells. Altogether, our results suggest that bromelain or bromelain rich pineapple stem may be used as an antiviral against COVID-19 MESHD.

    ACE HGNC inhibitors, AT1 receptor blockers and COVID-19 MESHD: clinical epidemiology evidences for a continuation of treatments. The ACER-COVID study

    Authors: Luc Dauchet; Marc Lambert; Victoria Gauthier; Julien Poissy; Karine Faure; Alain Facon; Cécile Yelnik; Sophie Panaget; Thierry Plagnieux; Florent Verfaillie; Daniel Mathieu; Patrick Goldstein; Aline Meirhaeghe; Philippe Amouyel

    doi:10.1101/2020.04.28.20078071 Date: 2020-05-01 Source: medRxiv

    Aims: The question of interactions between the renin angiotensin aldosterone system drugs and the incidence and prognosis of COVID-19 MESHD infection has been raised by the medical community. We hypothesised that if patients treated with ACE HGNC inhibitors (ACEI) or AT1 receptor blockers (ARB) were more prone to SARS-CoV2 infection MESHD and had a worse prognosis than untreated patients, the prevalence of consumption of these drugs would be higher in patients with COVID-19 MESHD compared to the general population. Methods and results: We used a clinical epidemiology approach based on the estimation of standardised prevalence ratio ( SPR HGNC) of consumption of ACEI and ARB in four groups of patients (including 187 COVID-19 MESHD positive) with increasing severity referred to the University hospital of Lille and in three French reference samples (the exhaustive North population (n=1,569,968), a representative sample of the French population (n=414,046), a random sample of Lille area (n=1,584)). The SPRs of ACEI and ARB did not differ as the severity of the COVID-19 MESHD patients increased, being similar to the regular consumption of these drugs in the North of France population with the same non-significant increase for both treatment (1.17 [0.83-1.67]). A statistically significant increase in the SPR HGNC of ARB (1.56 [1.02-2.39]) was observed in intensive care unit patients only. After stratification on obesity MESHD, this increase was limited to the high risk subgroup of obese MESHD patients. Conclusions: Our results strongly support the recommendation that ACEI and ARB should be continued in the population and in COVID-19 MESHD positive patients, reinforcing the position of several scientific societies.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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