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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (2227)

ProteinN (199)

NSP5 (65)

ProteinS1 (58)

ComplexRdRp (52)


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    Withanone from Withania somnifera May Inhibit Novel Coronavirus ( COVID-19 MESHD) Entry by Disrupting Interactions between Viral S-Protein PROTEIN Receptor Binding Domain and Host ACE2 Receptor

    Authors: Acharya Balkrishna; SUBARNA POKHREL; Jagdeep Singh; Anurag Varshney

    doi:10.21203/rs.3.rs-17806/v1 Date: 2020-03-17 Source: ResearchSquare

    Background Newly emerged COVID-19 MESHD has been shown to engage the host cell ACE2 through its spike protein PROTEIN receptor binding domain (RBD). Here we show that natural phytochemical from a medicinal herb, Withania somnifera, have distinct effects on viral RBD and host ACE2 receptor complex. Methods We employed molecular docking to screen thousands of phytochemicals against the ACE2-RBD complex, performed molecular dynamics (MD) simulation, and estimated the electrostatic component of binding free energy, along with the computation of salt bridge electrostatics. Results We report that W. somnifera compound, Withanone, docked very well in the binding interface of AEC2-RBD complex, and was found to move slightly towards the interface centre on simulation. Withanone significantly decreased electrostatic component of binding free energies of ACE2-RBD complex. Two salt bridges were also identified at the interface; incorporation of Withanone destabilized these salt bridges and decreased their occupancies MESHD. We postulate, such an interruption of electrostatic interactions between the RBD and ACE2 would block or weaken COVID-19 MESHD entry and its subsequent infectivity. Conclusion Our data, for the first time, show that natural phytochemicals could well be the viable options for controlling COVID-19 MESHD entry into host cells, and W. somnifera may be the first choice of herbs in these directions to curb the COVID-19 MESHD infectivity.

    The sequence of human ACE2 HGNC is suboptimal for binding the S spike protein PROTEIN of SARS coronavirus 2

    Authors: Erik Procko

    doi:10.1101/2020.03.16.994236 Date: 2020-03-17 Source: bioRxiv

    The rapid and escalating spread of SARS coronavirus MESHD 2 (SARS-CoV-2) poses an immediate public health emergency. The viral spike protein S PROTEIN binds ACE2 HGNC on host cells to initiate molecular events that release the viral genome intracellularly. Soluble ACE2 HGNC inhibits entry of both SARS and SARS-2 coronaviruses by acting as a decoy for S binding sites, and is a candidate for therapeutic, prophylactic and diagnostic development. Using deep mutagenesis, variants of ACE2 HGNC are identified with increased binding to the receptor binding domain of S. Mutations are found across the interface, in the N90-glycosylation motif, and at buried sites where they are predicted to enhance local folding and presentation of the interaction epitope. When single substitutions are combined, large increases in binding can be achieved. The mutational landscape offers a blueprint for engineering high affinity proteins and peptides that block receptor binding sites on S to meet this unprecedented challenge.

    Evidence of the Recombinant Origin and Ongoing Mutations in Severe Acute Respiratory Syndrome 2 (SARS-COV-2)

    Authors: Jiao-Mei Huang; Syed Sajid Jan; Xiaobin Wei; Yi Wan; Songying Ouyang

    doi:10.1101/2020.03.16.993816 Date: 2020-03-17 Source: bioRxiv

    The recent global outbreak of viral pneumonia MESHD designated as Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) by coronavirus (SARS-CoV-2) has threatened global public health and urged to investigate its source. Whole genome analysis of SARS-CoV-2 revealed ~96% genomic similarity with bat CoV (RaTG13) and clustered together in phylogenetic tree. Furthermore, RaTGl3 also showed 97.43% spike protein PROTEIN similarity with SARS-CoV-2 suggesting that RaTGl3 is the closest strain. However, RBD and key amino acid residues supposed to be crucial for human-to-human and cross-species transmission are homologues between SARS-CoV-2 and pangolin CoVs. These results from our analysis suggest that SARS-CoV-2 is a recombinant virus of bat and pangolin CoVs. Moreover, this study also reports mutations in coding regions of 125 SARS-CoV-2 genomes signifying its aptitude for evolution. In short, our findings propose that homologous recombination has been occurred between bat and pangolin CoVs that triggered cross-species transmission and emergence of SARS-CoV-2, and, during the ongoing outbreak, SARS-CoV-2 is still evolving for its adaptability.

    Cross-reactive antibody response between SARS-CoV-2 and SARS-CoV infections

    Authors: Huibin Lv; Nicholas C. Wu; Owen Tak-Yin Tsang; Meng Yuan; Ranawaka A. P. M. Perera; Wai Shing Leung; Ray T. Y. So; Jacky Man Chun Chan; Garrick K. Yip; Thomas Shiu Hong Chik; Yiquan Wang; Chris Yau Chung Choi; Yihan Lin; Wilson W. Ng; Jincun Zhao; Leo L. M. Poon; J. S. Malik Peiris; Ian A. Wilson; Chris K. P. Mok

    doi:10.1101/2020.03.15.993097 Date: 2020-03-17 Source: bioRxiv

    The World Health Organization has recently declared the ongoing outbreak of COVID-19 MESHD, which is caused by a novel coronavirus SARS-CoV-2, as pandemic. There is currently a lack of knowledge in the antibody response elicited from SARS-CoV-2 infection MESHD. One major immunological question is concerning the antigenic differences between SARS-CoV-2 and SARS-CoV. We address this question by using plasma from patients infected by SARS-CoV-2 or SARS-CoV MESHD, and plasma obtained from infected MESHD or immunized mice. Our results show that while cross-reactivity in antibody binding to the spike protein PROTEIN is common, cross-neutralization of the live viruses is rare, indicating the presence of non-neutralizing antibody response to conserved epitopes in the spike. Whether these non-neutralizing antibody responses will lead to antibody-dependent disease enhancement needs to be addressed in the future. Overall, this study not only addresses a fundamental question regarding the antigenicity differences between SARS-CoV-2 and SARS-CoV, but also has important implications in vaccine development.

    Predicting COVID-19 MESHD distribution in Mexico through a discrete and time-dependent Markov chain and an SIR-like model

    Authors: Alfonso Vivanco-Lira

    id:2003.06758v1 Date: 2020-03-15 Source: arXiv

    COVID-19 MESHD is an emergent viral infection which rose in December 2019 in a city in the Chinese province of Hubei, Wuhan; the viral aetiology of this infection is now known as COVID-19 MESHD virus, which belongs to the Betacoronavirus genus. This virus produces the syndrome of acute respiratory stress MESHD that h as been witnessed in other coronaviruses, such as that MERS-CoV in Middle East countries or SARS-CoV which was seen in 2002 and 2003 in China. This virus mediates its entry through its spike (S) proteins PROTEIN interacting with ACE2 receptors in lung epithelial cells, and may promote an inflammatory response by means of inflammasome NLRP3 activation and unfolded protein response (these are possibly consequence of the envelope E protein PROTEIN of COVID-19 MESHD virus). Efforts have been made worldwide to prevent further spread of the disease, but in March 2020 the WHO declared it a pandemic emergency and Mexico started to report its first cases. In this paper we attempt to summarize the biological features of the virus and the possible pathophysiological mechanisms of its disease, as well as a stochastic model characterizing the probability distribution of cases in Mexico by states and the estimated number of cases in Mexico through a differential equation model (modified SIR model), thus will we be able to characterize the disease and its course in Mexico in order to display more preparedness and promote more logical actions by both the policy makers as well as the general population.

    A highly conserved cryptic epitope in the receptor-binding domains of SARS-CoV-2 and SARS-CoV

    Authors: Meng Yuan; Nicholas C. Wu; Xueyong Zhu; Chang-Chun D. Lee; Ray T. Y. So; Huibin Lv; Chris K. P. Mok; Ian A. Wilson

    doi:10.1101/2020.03.13.991570 Date: 2020-03-14 Source: bioRxiv

    The outbreak of COVID-19 MESHD, which is caused by SARS-CoV-2 virus, continues to spread globally, but there is currently very little understanding of the epitopes on the virus. In this study, we have determined the crystal structure of the receptor-binding domain (RBD) of the SARS-CoV-2 spike PROTEIN ( S) protein PROTEIN in complex with CR3022, a neutralizing antibody previously isolated from a convalescent SARS patient. CR3022 targets a highly conserved epitope that enables cross-reactive binding between SARS-CoV-2 and SARS-CoV MESHD. Structural modeling further demonstrates that the binding site can only be accessed when at least two RBDs on the trimeric S protein PROTEIN are in the "up" conformation. Overall, this study provides structural and molecular insight into the antigenicity of SARS-CoV-2. ONE SENTENCE SUMMARYStructural study of a cross-reactive SARS antibody reveals a conserved epitope on the SARS-CoV-2 receptor-binding domain.

    SARS-CoV-2 invades host cells via a novel route: CD147 HGNC- spike protein PROTEIN

    Authors: Ke Wang; Wei Chen; Yu-Sen Zhou; Jian-Qi Lian; Zheng Zhang; Peng Du; Li Gong; Yang Zhang; Hong-Yong Cui; Jie-Jie Geng; Bin Wang; Xiu-Xuan Sun; Chun-Fu Wang; Xu Yang; Peng Lin; Yong-Qiang Deng; Ding Wei; Xiang-Min Yang; Yu-Meng Zhu; Kui Zhang; Zhao-Hui Zheng; Jin-Lin Miao; Ting Guo; Ying Shi; Jun Zhang; Ling Fu; Qing-Yi Wang; Huijie Bian; Ping Zhu; Zhi-Nan Chen

    doi:10.1101/2020.03.14.988345 Date: 2020-03-14 Source: bioRxiv

    Currently, COVID-19 MESHD caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely spread around the world; nevertheless, so far there exist no specific antiviral drugs for treatment of the disease, which poses great challenge to control and contain the virus. Here, we reported a research finding that SARS-CoV-2 invaded host cells via a novel route of CD147- spike protein PROTEIN (SP). SP bound to CD147 HGNC, a receptor on the host cells, thereby mediating the viral invasion. Our further research confirmed this finding. First, in vitro antiviral tests indicated Meplazumab, an anti- CD147 HGNC humanized antibody, significantly inhibited the viruses from invading host cells, with an EC50 of 24.86 g/mL and IC50 of 15.16 g/mL. Second, we validated the interaction between CD147 HGNC and SP, with an affinity constant of 1.85x10-7M. Co-Immunoprecipitation and ELISA also confirmed the binding of the two proteins. Finally, the localization of CD147 HGNC and SP was observed in SARS-CoV-2 infected MESHD Vero E6 cells by immuno-electron microscope. Therefore, the discovery of the new route CD147-SP for SARS-CoV-2 invading host cells provides a critical target for development of specific antiviral drugs.

    Differential Antibody Recognition by Novel SARS-CoV- 2 and SARS-CoV Spike PROTEIN Protein Receptor Binding Domains: Mechanistic Insights

    Authors: Filippo Marchetti; Giorgio Colombo

    doi:10.1101/2020.03.13.990267 Date: 2020-03-14 Source: bioRxiv

    The appearance of the novel betacoronavirus SARS-CoV-2 represents a major threat to human health, and its diffusion around the world is causing dramatic consequences. The knowledge of the 3D structures of SARS-CoV-2 proteins can facilitate the development of therapeutic and diagnostic molecules. Specifically, comparative analyses of the structures of SARS-CoV-2 proteins MESHD and homologous proteins from previously characterized viruses, such as SARS-CoV MESHD, can reveal the common and/or distinctive traits that underlie the mechanisms of recognition of cell receptors and of molecules of the immune system. Herein, we apply our recently developed energy-based methods for the prediction of antibody-binding epitopes and protein-protein interaction regions to the Receptor Binding Domain (RBD) of the Spike proteins PROTEIN from SARS-CoV-2 and SARS-CoV. Our analysis focusses only on the study of the structure of RBDs in isolation, without making use of any previous knowledge of binding properties. Importantly, our results highlight structural and sequence differences among the regions that are predicted to be immunoreactive and bind/elicit antibodies. These results provide a rational basis to the observation that several SARS-CoV RDB-specific monoclonal antibodies fail to appreciably bind the SARS-CoV-2 counterpart. Furthermore, we correctly identify the region of SARS-CoV-2 RBD that is engaged by the cell receptor ACE2 HGNC during viral entry into host cells. The data, sequences and structures we present here can be useful for the development of novel therapeutic and diagnostic interventions.

    SARS-CoV-2 Entry Genes Are Most Highly Expressed in Nasal Goblet and Ciliated Cells within Human Airways

    Authors: Waradon Sungnak; Ni Huang; Christophe Bécavin; Marijn Berg; HCA Lung Biological Network

    id:2003.06122v1 Date: 2020-03-13 Source: arXiv

    The SARS-CoV-2 coronavirus, the etiologic agent responsible for COVID-19 MESHD coronavirus disease MESHD, is a global threat. To better understand viral tropism, we assessed the RNA expression of the coronavirus receptor, ACE2 HGNC, as well as the viral S protein PROTEIN priming protease TMPRSS2 HGNC thought to govern viral entry in single-cell RNA-sequencing (scRNA-seq) datasets from healthy individuals generated by the Human Cell Atlas consortium. We found that ACE2 HGNC, as well as the protease TMPRSS2 HGNC, are differentially expressed in respiratory and gut epithelial cells. In-depth analysis of epithelial cells in the respiratory tree reveals that nasal epithelial cells, specifically goblet/secretory cells and ciliated cells, display the highest ACE2 HGNC expression of all the epithelial cells analyzed. The skewed expression of viral receptors/entry-associated proteins towards the upper airway may be correlated with enhanced transmissivity. Finally, we showed that many of the top genes associated with ACE2 HGNC airway epithelial expression are innate immune-associated, antiviral genes, highly enriched in the nasal epithelial cells. This association with immune pathways might have clinical implications for the course of infection and viral pathology, and highlights the specific significance of nasal epithelia in viral infection MESHD. Our findings underscore the importance of the availability of the Human Cell Atlas as a reference dataset. In this instance, analysis of the compendium of data points to a particularly relevant role for nasal goblet and ciliated cells as early viral targets and potential reservoirs of SARS-CoV-2 infection MESHD. This, in turn, serves as a biological framework for dissecting viral transmission and developing clinical strategies for prevention and therapy.

    Virus strain of a mild COVID-19 MESHD patient in Hangzhou representing a new trend in SARS-CoV-2 evolution related to Furin HGNC cleavage site

    Authors:

    doi:10.1101/2020.03.10.20033944 Date: 2020-03-13 Source: medRxiv

    We found, in our 788 confirmed COVID-19 MESHD patients, the decreased rate of severe/critical type, increased liver/kidney damage MESHD and prolonged period of nuclear acid positivity during virus dissemination, when compared with Wuhan. To investigate the underlining mechanism, we isolated one strain of SARS- CoV-2 (ZJ01) in mild COVID-19 MESHD patient and found the existence of 35 specific gene mutation by gene alignment. Further phylogenetic analysis and RSCU heat map results suggested that ZJ01 may be a potential evolutionary branch of SARS-CoV-2. We classified 54 strains of viruses worldwide (C/T type) based on the base (C or T) at positions 8824 and 28247. ZJ01 were both T at these two sites, becoming the only TT type currently identified in the world. The prediction of Furin HGNC cleavage site (FCS) and the sequence alignment of virus family indicated that FCS may be an important site of coronavirus evolution. ZJ01 had mutations near FCS (F1-2), which caused changes in the structure and the electrostatic distribution of the S protein PROTEIN surface, further affecting the binding capacity of Furin HGNC. Single cell sequencing and ACE2 HGNC- Furin HGNC co-expression results confirmed that Furin HGNC level was higher in the whole body, especially in glands, liver, kidney and colon MESHD while FCS may help SARS-CoV-2 infect MESHD these organs. The evolutionary pattern of SARS-CoV-2 towards FCS formation may result in its clinical symptom becoming closer to HKU-1 and OC43 (the source of FCS sequence-PRRA) caused influenza, further showing potential in differentiating into mild COVID-19 MESHD subtypes.

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SARS-CoV-2 Proteins


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