更新于：2024-11-01

HCoV-229E S protein

更新于：2024-11-01

基本信息

别名-

简介-

关联

项与 HCoV-229E S protein 相关的药物

6RBD-np

靶点

HCoV-229E S protein x SARS-CoV S protein x SARS-CoV-2 S protein x hCoV HKU1

作用机制

HCoV-229E S protein抑制剂 [+3]

在研机构

Korea University

原研机构

Korea University

在研适应症

冠状病毒感染

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 HCoV-229E S protein 相关的临床结果

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100 项与 HCoV-229E S protein 相关的转化医学

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0 项与 HCoV-229E S protein 相关的专利（医药）

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项与 HCoV-229E S protein 相关的文献（医药）

2022-06-01·Virology

Flavonols and dihydroflavonols inhibit the main protease activity of SARS-CoV-2 and the replication of human coronavirus 229E

Article

作者: Kisthardt, Samantha C ; Scholle, Frank ; Xie, De-Yu ; Zhu, Yue

Since December 2019, the deadly novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the current COVID-19 pandemic. To date, vaccines are available in the developed countries to prevent the infection of this virus; however, medicines are necessary to help control COVID-19. Human coronavirus 229E (HCoV-229E) causes the common cold. The main protease (M^pro) is an essential enzyme required for the multiplication of these two viruses in the host cells, and thus is an appropriate candidate to screen potential medicinal compounds. Flavonols and dihydroflavonols are two groups of plant flavonoids. In this study, we report docking simulation with two M^pro enzymes and five flavonols and three dihydroflavonols, in vitro inhibition of the SARS-CoV-2 M^pro, and in vitro inhibition of the HCoV 229E replication. The docking simulation results predicted that (+)-dihydrokaempferol, (+)- dihydroquercetin, (+)-dihydromyricetin, kaempferol, quercetin, myricentin, isoquercitrin, and rutin could bind to at least two subsites (S1, S1', S2, and S4) in the binding pocket and inhibit the activity of SARS-CoV-2 M^pro. Their affinity scores ranged from -8.8 to -7.4 (kcal/mol). Likewise, these compounds were predicted to bind and inhibit the HCoV-229E M^pro activity with affinity scores ranging from -7.1 to -7.8 (kcal/mol). In vitro inhibition assays showed that seven available compounds effectively inhibited the SARS-CoV-2 M^pro activity and their IC₅₀ values ranged from 0.125 to 12.9 μM. Five compounds inhibited the replication of HCoV-229E in Huh-7 cells. These findings indicate that these antioxidative flavonols and dihydroflavonols are promising candidates for curbing the two viruses.

2021-07-01·Journal of Assisted Reproduction and Genetics3区 · 医学

Expression map of entry receptors and infectivity factors for pan-coronaviruses in preimplantation and implantation stage human embryos

3区 · 医学

Article

作者: Modi, D ; Bhide, A ; Husein, A ; Chhabria, K ; Singh, D ; Colaco, S ; Sharma, R ; Mishra, A ; Singh, N ; Ashary, N ; Singh, A

PURPOSETo predict if developing human embryos are permissive to multiple coronaviruses.METHODWe analyzed publicly available single-cell RNA-seq datasets of human embryos for the known canonical and non-canonical receptors and spike protein cleavage enzymes for multiple coronaviruses like SARS-CoV, SARS-CoV-2, MERS-CoV, hCoV-229E, and hCoV-NL63. We also analyzed the expression of host genes involved in viral replication, host proteins involved in viral endosomal sorting complexes required for transport (ESCRT), genes of host proteins that physically interact with proteins of SARS-CoV-2, and the host genes essential for coronavirus infectivity.RESULTSOf the known receptors of SARS viruses, ACE2, BSG, GOLGA7, and ZDHHC5 were expressed in different proportions in the zygote, 4-cell, 8-cell, morula, and blastocysts including the trophectoderm. The MERS-CoV receptor, DPP4, and hCoV-229E receptor, ANPEP, were expressed mainly from the compact morula to the blastocyst stages. Transcripts of the MERS-CoV alternate receptor LGALS1 were detected in most cells at all stages of development. TMPRSS2 transcripts were detected in the epiblast, primitive endoderm, and trophectoderm, while transcripts of the endosomal proteases CTSL, CTSB, and FURIN were expressed in most cells at all stages of development. ACE2 and TMPRSS2 were co-expressed in a proportion of epiblast and trophectoderm cells. The embryonic cells expressed genes involved in ESCRT, viral replication, SARS-CoV-2 interactions, and coronavirus infectivity. The ACE2 and TMPRSS2 co-expressing cells were enriched in genes associated with lipid metabolism, lysosome, peroxisome, and oxidative phosphorylation pathways.CONCLUSIONPreimplantation and implantation stage human embryos could be permissive to multiple hCoVs.

2020-05-01·Respiratory Investigation

Inhibitory effects of glycopyrronium, formoterol, and budesonide on coronavirus HCoV-229E replication and cytokine production by primary cultures of human nasal and tracheal epithelial cells

Article

作者: Watanabe, Oshi ; Deng, Xue ; Momma, Haruki ; Shimotai, Yoshitaka ; Kawase, Tetsuaki ; Nishimura, Hidekazu ; Nomura, Kazuhiro ; Yamaya, Mutsuo ; Sugawara, Mitsuru ; Ichinose, Masakazu

BACKGROUNDCoronavirus 229E (HCoV-229E), one of the causes of the common cold, exacerbates chronic obstructive pulmonary disease (COPD) and bronchial asthma. Long-acting muscarinic antagonists and β₂-agonists and inhaled corticosteroids inhibit the exacerbation of COPD and bronchial asthma caused by infection with viruses, including HCoV-229E. However, the effects of these drugs on HCoV-229E replication and infection-induced inflammation in the human airway are unknown.METHODSPrimary human nasal (HNE) and tracheal (HTE) epithelial cell cultures were infected with HCoV-229E.RESULTSPretreatment of HNE and HTE cells with glycopyrronium or formoterol decreased viral RNA levels and/or titers, the expression of the HCoV-229E receptor CD13, the number and fluorescence intensity of acidic endosomes where HCoV-229E RNA enters the cytoplasm, and the infection-induced production of cytokines, including IL-6, IL-8, and IFN-β. Treatment of the cells with the CD13 inhibitor 2'2'-dipyridyl decreased viral titers. Pretreatment of the cells with a combination of three drugs (glycopyrronium, formoterol, and budesonide) exerted additive inhibitory effects on viral titers and cytokine production. Pretreatment of HNE cells with glycopyrronium or formoterol reduced the susceptibility to infection, and pretreatment with the three drugs inhibited activation of nuclear factor-kappa B p50 and p65 proteins. Pretreatment with formoterol increased cAMP levels and treatment with cAMP decreased viral titers, CD13 expression, and the fluorescence intensity of acidic endosomes.CONCLUSIONSThese findings suggest that glycopyrronium, formoterol, and a combination of glycopyrronium, formoterol, and budesonide inhibit HCoV-229E replication partly by inhibiting receptor expression and/or endosomal function and that these drugs modulate infection-induced inflammation in the airway.