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HGNC Genes

SARS-CoV-2 proteins

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    Genome-wide CRISPR activation screen identifies novel receptors for SARS-CoV-2 entry MESHD

    Authors: Shiyou Zhu; Ying Liu; Zhuo Zhou; Zhiying Zhang; Xia Xiao; Zhiheng Liu; Ang Chen; Xiaojing Dong; Feng Tian; Shihua Chen; Yiyuan Xu; Chunhui Wang; Qiheng Li; Xuran Niu; Qian Pan; Shuo Du; Junyu Xiao; Jianwei Wang; Wensheng Wei

    doi:10.1101/2021.04.08.438924 Date: 2021-04-09 Source: bioRxiv

    The ongoing pandemic of coronavirus disease 2019 MESHD ( COVID-19 MESHD) caused by severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) has been endangering worldwide public health and economy. SARS-CoV-2 infects MESHD a variety of tissues where the known receptor ACE2 HGNC is low or almost absent, suggesting the existence of alternative pathways for virus entry. Here, we performed a genome-wide barcoded-CRISPRa screen to identify novel host factors that enable SARS-CoV-2 infection MESHD. In addition to known host proteins, i.e PROTEIN. ACE2 HGNC, TMPRSS2 HGNC, and NRP1 HGNC, we identified multiple host components, among which LDLRAD3 HGNC, TMEM30A HGNC, and CLEC4G HGNC were confirmed as functional receptors for SARS-CoV-2. All these membrane proteins bind directly to spike's N-terminal domain ( NTD HGNC). Their essential and physiological roles have all been confirmed in either neuron or liver cells. In particular, LDLRAD3 HGNC and CLEC4G HGNC mediate SARS-CoV-2 entry MESHD and infection in a fashion independent of ACE2 HGNC. The identification of the novel receptors and entry mechanisms could advance our understanding of the multiorgan tropism of SARS-CoV-2, and may shed light on the development of the therapeutic countermeasures against COVID-19 MESHD.

    miR-24 targets SARS-CoV-2 co-factor Neuropilin-1 HGNC in human brain microvascular endothelial cells: Insights for COVID-19 MESHD neurological manifestations

    Authors: Pasquale Mone; Jessica Gambardella; Xujun Wang; Stanislovas S. Jankauskas; Alessandro Matarese; Gaetano Santulli

    doi:10.21203/rs.3.rs-192099/v1 Date: 2021-01-30 Source: ResearchSquare

    Neuropilin-1 HGNC is a transmembrane glycoprotein that has been implicated in several processes including angiogenesis and immunity. Recent evidence has also shown that it is implied in the cellular internalization of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) MESHD, which causes the coronavirus disease 2019 MESHD ( COVID-19 MESHD). We hypothesized that specific microRNAs can target Neuropilin-1 HGNC. By combining bioinformatic and functional approaches, we identified miR-24 as a regulator of Neuropilin-1 HGNC transcription. Since Neuropilin-1 HGNC has been shown to play a key role in the endothelium-mediated regulation of the blood-brain barrier, we validated miR-24 as a functional modulator of Neuropilin-1 HGNC in human brain microvascular endothelial cells (hBMECs), which are the most suitable cell line for an in vitro blood–brain barrier model.

    Deep RNA Sequencing of Intensive Care Unit Patients with COVID-19 MESHD

    Authors: Sean F Monaghan; Alger M Fredericks; Maximilian S Jentzsch; William G Cioffi; Maya Cohen; William G Fairbrother; Shivam J Gandhi; Elizabeth O Harrington; Gerard J Nau; Jonathan S Reichner; Corey E Ventetuolo; Mitchell M Levy; Alfred Ayala

    doi:10.1101/2021.01.11.21249276 Date: 2021-01-13 Source: medRxiv

    Purpose COVID-19 MESHD has impacted millions of patients across the world. Molecular testing occurring now identifies the presence of the virus at the sampling site: nasopharynx, nares, or oral cavity. RNA sequencing has the potential to establish both the presence of the virus and define the hosts response in COVID-19 MESHD. MethodsSingle center, prospective study of patients with COVID-19 MESHD admitted to the intensive care unit where deep RNA sequencing (>100 million reads) of peripheral blood with computational biology analysis was done. All patients had positive SARS-CoV-2 PCR. Clinical data was prospectively collected. ResultsWe enrolled fifteen patients at a single hospital. Patients were critically ill with a mortality of 47% and 67% were on a ventilator. All the patients had the SARS-CoV- MESHD2 RNA identified in the blood in addition to RNA from other viruses, bacteria, and archaea. The expression of many immune modulating genes, including PD-L1 HGNC and PD-L2 HGNC, were significantly different in patients who died from COVID-19 MESHD. Some proteins were influenced by alternative transcription and splicing events, as seen in HLA-C, HLA-E HGNC, NRP1 HGNC and NRP2 HGNC. Entropy calculated from alternative RNA splicing and transcription start/end predicted mortality in these patients. ConclusionsCurrent upper respiratory tract testing for COVID-19 MESHD only determines if the virus is present. Deep RNA sequencing with appropriate computational biology may provide important prognostic information and point to therapeutic foci to be precisely targeted in future studies. Take Home MessageDeep RNA sequencing provides a novel diagnostic tool for critically ill MESHD patients. Among ICU patients with COVID-19 MESHD, RNA sequencings can identify gene expression, pathogens (including SARS-CoV-2), and can predict mortality. TweetDeep RNA sequencing is a novel technology that can assist in the care of critically ill COVID-19 MESHD patients & can be applied to other disease

    Neuropilin-1 HGNC Assists SARS-CoV-2 Infection MESHD by Stimulating the Separation of Spike Protein PROTEIN Domains S1 and S2

    Authors: Zhenlu Li; Matthias Buck; Pei Hao; Xintian Xu; Lina Song; Simo Kitanovski; Jun Wang; Matthias Buck; Aaron Weinberg; Chun-Che Liao; Yen-Hui Chen; Jia-Tsrong Jan; Cheng-Pu Sun; Yin-Shiou Lin; Ping-Yi Wu; Yu-Chiuan Wang; Mi-Hua Tao; Yi-Ling Lin

    doi:10.1101/2021.01.06.425627 Date: 2021-01-07 Source: bioRxiv

    The cell surface receptor Neuropilin-1 ( Nrp1 HGNC) was recently identified as a host factor for SARS-CoV-2 entry. As the Spike protein PROTEIN of SARS-Cov-2 is cleaved into the S1 and the S2 domain by furin protease, Nrp1 HGNC binds to the newly created C-terminal RRAR amino acid sequence of the S1 domain. In this study, we model the association of a Nrp1 HGNC (a2-b1-b2) protein with the Spike PROTEIN protein computationally and analyze the topological constraints in the SARS-CoV-2 Spike PROTEIN SARS-CoV-2 Spike MESHD protein for binding with Nrp1 HGNC and ACE2 HGNC. Importantly, we study the exit mechanism of S2 from the S1 domain with the assistance of ACE2 HGNC as well as Nrp1 HGNC by molecular dynamics pulling simulations. In the presence of Nrp1 HGNC, by binding the S1 more strongly to the host membrane, there is a high probability of S2 being pulled out, rather than S1 being stretched. Thus, Nrp1 HGNC binding could stimulate the exit of S2 from the S1 domain, which will likely increase virus infectivity as the liberated S2 domain mediates the fusion of virus and host membranes. Understanding of such a Nrp1 HGNC-assisted viral infection opens the gate for the generation of protein-protein inhibitors, such as antibodies, which could attenuate the infection mechanism and protect certain cells in a future combination therapy.

    In Silico Docking for Inhibition Neuropilin-1 HGNC (SARS-CoV-2 receptor) by Some Natural and Approved Drugs

    Authors: mohamed seadawy; Mohamed Shamel; Aya Ahmed; Abdel Rahman N. Zekri

    doi:10.21203/rs.3.rs-118263/v1 Date: 2020-11-29 Source: ResearchSquare

    Background: Neuropilin-1 HGNC ( NRP-1 HGNC) is a multifunctional transmembrane receptor for ligands that affect developmental axonal growth MESHD and angiogenesis. Beside its role in cancer MESHD, NRP-1 HGNC is a reported entrance for several viruses, including severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), the causal agent of coronavirus disease 2019 MESHD ( COVID-19 MESHD). Methods: We made Insilco docking between the spike protein PROTEIN and Neuropilin-1 HGNC using Cluspro 2.0 software. Therefore, Neuropilin-1 HGNC becomes host factor for SARS-CoV-2 infection MESHD. Then by using molecular docking, we test nine compounds against Neuropilin-1 HGNC for its inhibition. Results: Our result revealed that NRP-1 receptor is considered as Therapeutic target for SARS-CoV2 treatment and screened with natural compounds and drugs (e.g. Carvacrol, Thymol, Amantadine, Daclatasvir, Ravidasvir, Remdesivir, Sofosbuvir, Hesperidine and Thymoquinone) by molecular docking study. Conclusion: These natural products and drugs may emerge as potential Neuropilin-1 HGNC inhibitor. However, additional exploration is predictable for the investigation of the essential use of the drugs and herbs containing these natural products and their in-vivo activity.

    In Silico Docking for Inhibition Neuropilin-1 HGNC (SARS-CoV-2 Receptor) by Some Natural and Approved Drugs

    Authors: Mohamed G.Seadawy; Mohamed Shamel; Aya Ahmed; Abdel Rahman N. Zekri

    doi:10.21203/rs.3.rs-111160/v1 Date: 2020-11-18 Source: ResearchSquare

    Severe Acute Respiratory Syndrome MESHD Coronavirus2 (SARS-CoV-2) attached to Angiotensin Converting Enzyme 2 HGNC ( ACE2 HGNC) as human receptor. The Spike (S) protein PROTEIN of this virus is responsible for host cell penetration and attachment. This viral glycoprotein is synthesized as a precursor in infected cells and, to be active, must be cleaved to two associated polypeptides: S1 and S2 1, 2. We made Insilco docking between the spike protein PROTEIN and Neuropilin-1 HGNC using Cluspro 2.0 software. Therefore, Neuropilin-1 HGNC becomes host factor for SARS-CoV-2 infection MESHD. Our study revealed that some drugs and natural compounds success in inhibition of binding between the virus and its new receptor with Insilco docking data. 

    In silico identification and validation of inhibitors of the interaction between neuropilin receptor 1 and SARS-CoV-2 Spike PROTEIN protein

    Authors: Samantha Perez-Miller; Marcel Patek; Aubin Moutal; Carly R Cabel; Curtis A. Thorne; Samuel K Campos; Rajesh Khanna

    doi:10.1101/2020.09.22.308783 Date: 2020-09-23 Source: bioRxiv

    Neuropilin-1 HGNC ( NRP-1 HGNC) is a multifunctional transmembrane receptor for ligands that affect developmental axonal growth MESHD and angiogenesis. In addition to a role in cancer MESHD, NRP-1 HGNC is a reported entry point for several viruses, including severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), the causal agent of coronavirus disease 2019 MESHD ( COVID-19 MESHD). The furin cleavage product of SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN protein takes advantage of the vascular endothelial growth factor A HGNC ( VEGF-A HGNC) binding site on NRP-1 HGNC which accommodates a polybasic stretch ending in a C-terminal arginine. This site has long been a focus of drug discovery efforts for cancer MESHD therapeutics. We recently showed that interruption of the VEGF-A HGNC/ NRP-1 HGNC signaling pathway ameliorates neuropathic pain MESHD and hypothesize that interference of this pathway by SARS-CoV-2 spike PROTEIN protein interferes with pain MESHD signaling. Here, we report hits from a small molecule and natural product screen of nearly 0.5 million compounds targeting the VEGF-A HGNC binding site on NRP-1 HGNC. We identified nine chemical series with lead- or drug-like physico-chemical properties. Using an ELISA, we demonstrate that six compounds disrupt VEGF-A-NRP-1 binding more effectively than EG00229, a known NRP-1 HGNC inhibitor. Secondary validation in cells revealed that almost all tested compounds inhibited VEGF-A HGNC triggered VEGFR2 HGNC phosphorylation. Two compounds displayed robust inhibition of a recombinant vesicular stomatitis MESHD virus protein that utilizes the SARS-CoV-2 Spike PROTEIN for entry and fusion. These compounds represent a first step in a renewed effort to develop small molecule inhibitors of the VEGF-A HGNC/ NRP-1 HGNC signaling for the treatment of neuropathic pain MESHD and cancer MESHD with the added potential of inhibiting SARS-CoV-2 virus entry.

    SARS-CoV-2 Spike PROTEIN protein hijacks VEGF-A HGNC/Neuropilin-1 receptor signaling to induce analgesia

    Authors: Aubin Moutal; Laurent F Martin; Lisa Boinon; Kimberly Gomez; Dongzhi Ran; Yuan Zhou; Harrison J Stratton; Cai Song; Shizhen Luo; Kerry Beth Gonzalez; Samantha Perez-Miller; Amol Patwardhan; Mohab Ibrahim; Rajesh Khanna

    doi:10.1101/2020.07.17.209288 Date: 2020-07-18 Source: bioRxiv

    Global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues unabated. Binding of SARS-CoV-2s Spike MESHD Spike protein PROTEIN to host angiotensin converting enzyme 2 triggers viral entry, but other proteins may participate, including neuropilin-1 receptor ( NRP-1 HGNC). As both Spike protein PROTEIN and vascular endothelial growth factor-A (VEGF-A) - a pronociceptive and angiogenic factor, bind NRP-1 HGNC, we tested if Spike could block VEGF-A HGNC/ NRP-1 HGNC signaling. VEGF-A HGNC-triggered sensory neuronal firing was blocked by Spike protein PROTEIN and NRP-1 HGNC inhibitor EG00229. Pro-nociceptive behaviors of VEGF-A HGNC were similarly blocked via suppression of spontaneous spinal synaptic activity and reduction of electrogenic currents in sensory neurons. Remarkably, preventing VEGF-A HGNC/ NRP-1 HGNC signaling was antiallodynic in a neuropathic pain MESHD model. A silencing of pain MESHD via subversion of VEGF-A HGNC/ NRP-1 HGNC signaling may underlie increased disease transmission in asymptomatic individuals. One Sentence SummarySARS-CoV-2s Spike protein PROTEIN promotes analgesia by interfering with VEGF-A HGNC/ NRP1 HGNC pathway, which may affect disease transmission dynamics.

    Neuropilin-1 HGNC facilitates SARS-CoV-2 cell entry and provides a possible pathway into the central nervous system

    Authors: Ludovico Cantuti-Castelvetri; Ravi Ohja; Liliana Pedro; Minou Djannatian; Jonas Franz; Suvi Kuivanen; Katri Kallio; Tugberg Kaya; Maria Anastasina; Teemu Smura; Lev Levanov; Leonora Szirovicza; Allan Tobi; Hannimari Kallio-Kokko; Pamela Osterlund; Merja Joensuu; Frederic Meunier; Sarah Butcher; Martin Winkler; Brit Mollenhauer; Ari Helenius; Ozgun Gokce; Tambet Teesalu; Jussi Hepojoki; Olli Vapalahti; Christine Stadelmann; Giuseppe Balistreri; Mikael Simons

    doi:10.1101/2020.06.07.137802 Date: 2020-06-07 Source: bioRxiv

    The causative agent of the current pandemic and coronavirus disease 2019 MESHD ( COVID-19 MESHD) is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1. Understanding how SARS-CoV-2 enters and spreads within human organs is crucial for developing strategies to prevent viral dissemination. For many viruses, tissue tropism is determined by the availability of virus receptors on the surface of host cells2. Both SARS-CoV MESHD and SARS-CoV-2 use angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC) as a host receptor, yet, their tropisms differ3-5. Here, we found that the cellular receptor neuropilin-1 HGNC ( NRP1 HGNC), known to bind furin-cleaved substrates, significantly potentiates SARS-CoV-2 infectivity MESHD, which was inhibited by a monoclonal blocking antibody against the extracellular b1b2 domain of NRP1 HGNC. NRP1 HGNC is abundantly expressed in the respiratory and olfactory epithelium, with highest expression in endothelial cells and in the epithelial cells facing the nasal cavity. Neuropathological analysis of human COVID-19 MESHD autopsies revealed SARS-CoV-2 infected MESHD NRP1 HGNC-positive cells in the olfactory epithelium and bulb. In the olfactory bulb infection MESHD was detected particularly within NRP1 HGNC-positive endothelial cells of small capillaries and medium-sized vessels. Studies in mice demonstrated, after intranasal application, NRP1-mediated transport of virus-sized particles into the central nervous system. Thus, NRP1 could explain the enhanced tropism and spreading of SARS-CoV-2.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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