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HGNC Genes

SARS-CoV-2 proteins

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    Bioactive Agents Contained in Different Nasal Sprays May Defeat SARS-Cov-2: A Repurposing and In-Silico Approach

    Authors: Mohammad Faheem Khan; Waseem Ahmad Ansari; Tanveer Ahamad; Mohsin Ali Khan; Zaw Ali Khan; Aqib Sarfraz; Mohd Aamish Khan

    doi:10.21203/rs.3.rs-135981/v1 Date: 2020-12-25 Source: ResearchSquare

    Recently, Coronavirus Disease 2019 MESHD ( COVID-19 MESHD), caused by fast-spreading and highly contagious severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2), has been declared as a pandemic disease of the 21st century by the World Health Organization (WHO). SARS-CoV-2 enters into the human respiratory system by binding of the viral surface spike glycoprotein PROTEIN ( S-protein PROTEIN S-protein HGNC) to angiotensin-converting enzyme2 HGNC ( ACE2 HGNC) receptor that is found in the nasal passage and oral cavity of a human. Both spike protein PROTEIN and the ACE2 HGNC receptor have been identified as promising therapeutic targets to develop anti-SARS-CoV-2 drugs. Although in the last few months, various studies have identified some promising molecules against both the receptors including human ACE2 HGNC and SARS-CoV-2 spike PROTEIN protein, still there is no vaccine or therapeutic drugs as of today. The repurposing of FDA-approved drugs may provide a rapid and potential treatment to combat COVID-19 MESHD by using high throughput virtual screening approach. In the present study, we have used the repurposing approach for bioactive agents of the nasal spray against human ACE2 HGNC and SARS-CoV-2 spike PROTEIN protein to identify the anti- COVID-19 MESHD agents with the help of molecular docking study. To this, we screened the sixteen bioactive agents of the nasal spray by analyzing their binding free energy and binding mode through molecular docking study. As a result, bioactive agents such as ciclesonide, levocabastine, and triamcinolone acetonide were found as highly active ligands with potent binding affinities against both the targets human ACE2 HGNC and SARS-CoV-2 spike PROTEIN proteins. Thus, these bioactive agents may effectively assist to control the COVID-19 MESHD by inhibiting the human ACE2 HGNC receptor as well as spike protein PROTEIN of SARS-CoV-2.

    A first-in-human evaluation of the safety and immunogenicity of SCB-2019, an adjuvanted, recombinant SARS-CoV-2 trimeric S-protein PROTEIN S-protein HGNC subunit vaccine for COVID-19 MESHD in healthy adults; a phase 1, randomised, double-blind, placebo-controlled trial

    Authors: Peter Richmond; Lara Hetchual; Min Dong; Brenda Ma; Branda Hu; Igor Smolenov; Ping Li; Peng Liang; Htay Htay Han; Joshua Liang; Ralf Clemens

    doi:10.1101/2020.12.03.20243709 Date: 2020-12-04 Source: medRxiv

    BackgroundAs part of the accelerated development of prophylactic vaccines against severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) we report a first-in-human dose-finding and adjuvant justification study of SCB-2019, a novel protein subunit vaccine candidate composed of a stabilised trimeric form of the spike (S)-protein PROTEIN produced in CHO-cells, combined with two different adjuvants. MethodsThis phase 1 study was done in one centre in Western Australia in 151 healthy adult volunteers in two age groups (18-54 and 55-75 years), allocated to 15 groups (nine young and six older adults) to receive two doses, 21 days apart, of placebo, or 3 g, 9 g or 30 g SCB-2019, alone or adjuvanted with AS03 or CpG/Alum. Reactogenicity was assessed for 7 days after each vaccination. Humoral responses were measured as SCB-2019 binding and ACE2-competitive binding IgG antibodies by ELISA, and as neutralising antibodies by wild-type SARS-CoV-2 microneutralisation assay; cellular responses to pooled S-protein HGNC S-protein PROTEIN peptides were measured by flow-cytometric intracellular cytokine staining. FindingsWe report on 148 participants with at least 4 weeks follow-up post dose 2. Three participants withdrew, two for personal reasons and one with an unrelated SAE (pituitary adenoma MESHD). Vaccination was well tolerated, with few Grade 3 solicited adverse events (AE). Most local AEs MESHD were mild injection site pain MESHD, which were more frequent with formulations containing AS03 than CpG/Alum or unadjuvanted SCB-2019. Systemic AEs MESHD, mostly transient headache MESHD, fatigue MESHD or myalgia MESHD, were more frequent in young adults than older adults after the first dose, but similar after second doses. Unadjuvanted SCB-2019 elicited minimal immune responses, but SCB-2019 with fixed doses of AS03 or CpG/Alum induced high titres and seroconversion rates of binding and neutralising antibodies in both young and older adults. Titres were higher than those observed in a panel of COVID-19 MESHD convalescent sera in all AS03 groups and high dose CpG/Alum groups. Both adjuvanted formulations elicited Th1-biased CD4+ T cell responses. InterpretationSCB-2019 trimeric protein formulated with AS03 or CpG/Alum adjuvants elicited robust humoral and cellular immune responses against SARS-CoV-2 with high viral neutralising activity. Both adjuvanted formulations were well tolerated and are suitable for further clinical development. Clinical trial registrationClinicalTrials.gov identifier NCT04405908.

    Humoral Response Dynamics Following Infection with SARS-CoV-2

    Authors: Louis Grandjean; Anja Saso; Arturo Ortiz; Tanya Lam; James Hatcher; Rosie Thistlethwaite; Mark Harris; Timothy Best; Marina Johnson; Helen Wagstaffe; Elizabeth Ralph; Annabelle Mai; Caroline Colijn; Judith Breuer; Matthew Buckland; Kimberly Gilmour; David Goldblatt; - The Co-Stars Study Team

    doi:10.1101/2020.07.16.20155663 Date: 2020-07-21 Source: medRxiv

    Introduction: Severe Acute Respiratory Syndrome Coronavirus-2 MESHD (SARS-CoV-2) specific antibodies have been shown to neutralize the virus in-vitro. Understanding antibody dynamics following SARS-CoV-2 infection MESHD is therefore crucial. Sensitive measurement of SARS-CoV-2 antibodies is also vital for large seroprevalence surveys which inform government policies and public health interventions. However, rapidly waning antibodies following SARS-CoV-2 infection MESHD could jeopardize the sensitivity of serological testing on which these surveys depend. Methods: This prospective cohort study of SARS-CoV-2 humoral dynamics in a central London hospital analyzed 137 serial samples collected from 67 participants seropositive to SARS-CoV-2 by the Meso-Scale Discovery assay. Antibody titers were quantified to the SARS-CoV-2 nucleoprotein (N PROTEIN), spike (S-)protein PROTEIN S-)protein HGNC and the receptor-binding-domain (RBD) of the S-protein HGNC S-protein PROTEIN. Titers were log-transformed and a multivariate log-linear model with time-since-infection and clinical variables was fitted by Bayesian methods. Results: The mean estimated half-life of the N-antibody was 52 days (95% CI 42-65). The S- and RBD-antibody had significantly longer mean half-lives of 81 days (95% CI 61-111) and 83 days (95% CI 55-137) respectively. An ACE-2-receptor competition assay demonstrated significant correlation between the S and RBD-antibody titers and ACE2-receptor blocking in-vitro. The time-to-a-negative N-antibody test for 50% of the seropositive population was predicted to be 195 days (95% CI 163-236). Discussion: After SARS-CoV-2 infection MESHD, the predicted half-life of N-antibody was 52 days with 50% of seropositive participants becoming seronegative to this antibody at 195 days. Widely used serological tests that depend on the N-antibody will therefore significantly underestimate the prevalence of infection following the majority of infections.

    Identification of SARS-CoV-2 Cell Entry Inhibitors by Drug Repurposing Using in Silico Structure-Based Virtual Screening Approach

    Authors: Shweta Choudhary; Yashpal S. Malik; Shailly Tomar

    doi:10.26434/chemrxiv.12005988.v2 Date: 2020-04-15 Source: ChemRxiv

    The rapidly spreading, highly contagious and pathogenic SARS-coronavirus MESHD 2 (SARS-CoV-2) associated Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) has been declared as a pandemic by the World Health Organization (WHO). The novel 2019 SARS-CoV-2 enters the host cell by binding of the viral surface spike glycoprotein PROTEIN ( S-protein HGNC S-protein PROTEIN) to angiotensin converting enzyme 2 HGNC ( ACE2 HGNC). The virus specific molecular interaction with the host cell represents a promising therapeutic target for identifying SARS-CoV-2 antiviral drugs. The repurposing of drugs can provide a rapid and potential cure towards exponentially expending COVID-19 MESHD. Thereto, high-throughput virtual screening approach was used to investigate FDA approved LOPAC library drugs against both the S-protein HGNC S-protein PROTEIN and ACE2 HGNC host cell receptor. Primary screening identified a few promising drugs for both the targets, which were further analyzed in details by their binding energy, binding modes through molecular docking, dynamics and simulations. Evidently, Eptifibatide acetate, TNP, GNF5, GR 127935 hydrochloride hydrate and RS504393 were found binding to virus binding motifs of ACE2 HGNC receptor. Additionally, KT185, KT203 GSK1838705A, BMS195614, and RS504393 were identified to bind at the receptor binding site on the viral S-protein HGNC S-protein PROTEIN. These identified drug molecules may effectively assist in controlling the rapid spread of SARS-COV-2 by not only potentially inhibiting the virus at entry step but also as anti-inflammatory agents which could impart relief in lung injuries MESHD. Timely identification and determination of an effective drug to combat and tranquilize the COVID-19 MESHD global crisis is the utmost need of hour. Further, prompt in vivo testing to validate the anti-SARS-COV-2 inhibition by these drugs could save lives is justified.

    Human ACE2 HGNC receptor polymorphisms predict SARS-CoV-2 susceptibility

    Authors: Eric W Stawiski; Devan Diwanji; Kushal Suryamohan; Ravi Gupta; Frederic A Fellouse; Fah Sathirapongsasuti; Jiang Liu; Ying-Ping Jiang; Aakrosh Ratan; Monika Mis; Devi Santhosh; Sneha Somasekar; Sangeetha Mohan; Sameer Phalke; Boney Kuriakose; Aju Antony; Jagath R Junutula; Stephan C Schuster; Natalia Jura; Somasekar Seshagiri

    doi:10.1101/2020.04.07.024752 Date: 2020-04-10 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease MESHD ( COVID-19 MESHD) that has resulted in a global pandemic. It is a highly contagious positive strand RNA virus and its clinical presentation includes severe to critical respiratory disease MESHD that appears to be fatal in [~]3-5% of the cases. The viral spike (S) coat protein engages the human angiotensin-converting enzyme2 HGNC ( ACE2 HGNC) cell surface protein to invade the host cell. The SARS-CoV-2 S-protein PROTEIN S-protein HGNC has acquired mutations that increase its affinity to human ACE2 HGNC by [~]10-15-fold compared to SARS-CoV S-protein MESHD S-protein PROTEIN S-protein HGNC, making it highly infectious. In this study, we assessed if ACE2 HGNC polymorphisms might alter host susceptibility to SARS-CoV-2 by affecting the ACE2 S-protein PROTEIN interaction. Our comprehensive analysis of several large genomic datasets that included over 290,000 samples representing >400 population groups identified multiple ACE2 HGNC protein-altering variants, some of which mapped to the S-protein PROTEIN S-protein HGNC-interacting ACE2 HGNC surface. Using recently reported structural data and a recent S-protein HGNC S-protein PROTEIN-interacting synthetic mutant map of ACE2 HGNC, we have identified natural ACE2 HGNC variants that are predicted to alter the virus-host interaction and thereby potentially alter host susceptibility. In particular, human ACE2 HGNC variants S19P, I21V, E23K, K26R, T27A, N64K, T92I, Q102P and H378R are predicted to increase susceptibility. The T92I variant, part of a consensus NxS/T N-glycosylation motif, confirmed the role of N90 glycosylation in immunity from non-human CoVs. Other ACE2 HGNC variants K31R, N33I, H34R, E35K, E37K, D38V, Y50F, N51S, M62V, K68E, F72V, Y83H, G326E, G352V, D355N, Q388L and D509Y are putative protective variants predicted to show decreased binding to SARS-CoV-2 S-protein PROTEIN S-protein HGNC. Overall, ACE2 HGNC variants are rare, consistent with the lack of selection pressure given the recent history of SARS-CoV MESHD epidemics, however, are likely to play an important role in altering susceptibility to CoVs.

    Fast assessment of human receptor-binding capability of 2019 novel coronavirus (2019-nCoV)

    Authors: Qiang Huang; Andreas Herrmann

    doi:10.1101/2020.02.01.930537 Date: 2020-02-03 Source: bioRxiv

    The outbreaks of 2002/2003 SARS, 2012/2015 MERS and 2019/2020 Wuhan respiratory syndrome MESHD clearly indicate that genome evolution of an animal coronavirus (CoV) may enable it to acquire human transmission ability, and thereby to cause serious threats to global public health. It is widely accepted that CoV human transmission is driven by the interactions of its spike protein (S PROTEIN S-protein HGNC) with human receptor on host cell surface; so, quantitative evaluation of these interactions may be used to assess the human transmission capability of CoVs. However, quantitative methods directly using viral genome data are still lacking. Here, we perform large-scale protein-protein docking to quantify the interactions of 2019-nCoV S-protein HGNC S-protein PROTEIN receptor-binding domain (S-RBD) with human receptor ACE2 HGNC, based on experimental SARS-CoV S-RBD MESHD- ACE2 HGNC complex structure. By sampling a large number of thermodynamically probable binding conformations with Monte Carlo algorithm, this approach successfully identified the experimental complex structure as the lowest-energy receptor-binding conformations, and hence established an experiment-based strength reference for evaluating the receptor-binding affinity of 2019-nCoV via comparison with SARS-CoV MESHD. Our results show that this binding affinity is about 73% of that of SARS-CoV MESHD, supporting that 2019-nCoV may cause human transmission similar to that of SARS-CoV MESHD. Thus, this study presents a method for rapidly assessing the human transmission capability of a newly emerged CoV and its mutant strains, and demonstrates that post-genome analysis of protein-protein interactions may provide early scientific guidance for viral prevention and control.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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