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HGNC Genes

SARS-CoV-2 proteins

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    In Silico studies of Natural compounds that inhibit SARS-CoV-2 Nucleocapsid Nsp1 HGNC/ Nsp3 HGNC proteins mediated Viral Replication and Pathogenesis

    Authors: Hemanth Kumar Manikyam

    doi:10.21203/rs.3.rs-103400/v1 Date: 2020-11-05 Source: ResearchSquare

    Highly Transmissible and pathogenic coronavirus that emerged in late December of 2019 caused Severe acute respiratory syndrome MESHD (SARS-CoV-2), which challenged human health and public safety. Severity of the disease depends on the viral load and the type of mutation that occurred in the coronavirus. Nonstructural proteins like, Nsp1 HGNC, Nsp3 HGNC, Nsp12 and Nsp13 including other viral proteins plays important role during viral replication life cycle. Viral Replication initiated by hacking the host cellular mechanism either by synergy or by suppression using nucleocapsid proteins PROTEIN of the virus. Spike (S) protein PROTEIN of the SARS-CoV-2 uses angiotensin-converting enzyme II ( ACE2 HGNC) and TRMPSS as a cell entry. Once virus enters host cell, nucleocapsid proteins PROTEIN along with its genome is releases from endosomes into cytosol of the host cell. Ca2+/ CaM HGNC ( Calmodulin HGNC)/Calcineurin complex of the host cell plays important role during viral replication which is mediated by nucleocapsid proteins PROTEIN of the virus. Nsp1 HGNC/ Nsp3 HGNC nonstructural proteins triggers synergetic activity with CD147 HGNC/ CyPA HGNC/ HSPG HGNC pathway and TRMP2/ADPr/Ca+2 mediated Ca2+/CaM ( Calmodulin HGNC)/Calcineurin synthesis and free radicle generation in mitochondria leading to viral replication and severe chemokine activation pathways. Docking studies were carried out to inhibit Cyclophilin A and TRMP2 proteins as drug targets. Natural compounds like Withanolide A, Columbin, Cucurbitacin E, Boswellic acid along with Cyclosporines, Vitamin E and N-Acetyl cysteine ( NAC HGNC) were selected as ligands to study docking studies. Withanolide A and Cyclosporines had shown good inhibition activity against Cyclophilin A, whereas Columbin, Boswellic acid, Cucurbitacin E, Vitamin E and N-Acetyl cysteine ( NAC HGNC) had shown inhibitory activity against TRMP2. Thus, we suggest conducting further studies to conclude above pathways mechanism and inhibitory effect of natural compounds against the Nsp1 HGNC/ Nsp3 HGNC mediated pathways Invitro and In vivo.

    Targeting heparan sulfate proteoglycan-assisted endocytosis as a COVID-19 MESHD therapeutic option

    Authors: Qi Zhang; Catherine Chen; Manju Swaroop; Miao Xu; Lihui Wang; Juhyung Lee; Manisha Pradhan; Min Shen; Zhiji Luo; Yue Xu; Wenwei Huang; Wei Zheng; Yihong Ye

    doi:10.1101/2020.07.14.202549 Date: 2020-07-14 Source: bioRxiv

    Drugs capable of blocking the infectious cycle of the coronavirus SARS-CoV-2 are urgently needed to tackle the ongoing COVID-19 MESHD COVID-19 MESHD pandemic. To this end, the cell entry of SARS-CoV-2, initiated by the binding of the viral Spike (S) protein PROTEIN to human ACE2 HGNC, has emerged as an attractive drug repurposing target. Here we use murine leukemia MESHD viruses pseudotyped with Spike from SARS-CoV or SARS-CoV-2 MESHD to demonstrate that ACE2 HGNC-mediated coronavirus entry can be mitigated by heparin, a heparan sulfate-related glycan, or by genetic ablation of biosynthetic enzymes for the cell surface heparan sulfate proteoglycans (HSPGs). A drug repurposing screen targeting HSPG HGNC-dependent endocytosis identifies pharmacologically active endocytosis inhibitors that also abrogate coronavirus cell entry. Among them, Mitoxantrone (EC50=~10 nM) targets HSPGs directly, whereas Sunitinib and BNTX disrupt the actin network to impair HSPG HGNC-assisted viral entry. Gene expression profiling suggests potential combination regimens that optimally target HSPG HGNC-dependent viral entry. Altogether, our study establishes HSPGs as an assisting factor for ACE2 HGNC in endocytosis-mediated coronavirus entry and identifies drugs that can be repurposed to target this important stage in the viral life cycle.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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