HTCC: Broad Range Inhibitor of Coronavirus Entry.

HTCC: Broad Range Inhibitor of Coronavirus Entry.
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DOI:
10.1371/journal.pone.0156552
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发表时间:
2016
期刊:
影响因子:
3.7
通讯作者:
Pyrc K
Pyrc K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Milewska A;Kaminski K;Ciejka J;Kosowicz K;Zeglen S;Wojarski J;Nowakowska M;Szczubiałka K;Pyrc K

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迄今为止,已知有六种人类冠状病毒,它们都与人类呼吸道感染有关。除了高致病性SARS和MERS冠状病毒外,人类冠状病毒(HCoV-NL 63,HCoV-OC 43,HCoV-229 E和HCoV-HKU 1)在世界范围内传播,通常引起普通感冒。在大多数情况下,感染这些病毒不会导致严重疾病,尽管婴儿、老年人和免疫功能低下患者的急性感染可能进展为需要住院治疗的严重疾病。重要的是,目前还没有针对人类冠状病毒的药物,只有支持性治疗。以前,我们提出了阳离子改性的壳聚糖,N-(2-羟丙基)-3-三甲基铵壳聚糖氯化物(HTCC),及其疏水改性的衍生物(HM-HTCC)作为冠状病毒HCoV-NL 63的有效抑制剂。在这里,我们表明,HTCC抑制病毒与其受体的相互作用,从而阻止进入。此外,我们证明了具有不同取代度的HTCC聚合物可作为所有低致病性人类冠状病毒的有效抑制剂。
To date, six human coronaviruses have been known, all of which are associated with respiratory infections in humans. With the exception of the highly pathogenic SARS and MERS coronaviruses, human coronaviruses (HCoV-NL63, HCoV-OC43, HCoV-229E, and HCoV-HKU1) circulate worldwide and typically cause the common cold. In most cases, infection with these viruses does not lead to severe disease, although acute infections in infants, the elderly, and immunocompromised patients may progress to severe disease requiring hospitalization. Importantly, no drugs against human coronaviruses exist, and only supportive therapy is available. Previously, we proposed the cationically modified chitosan, N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC), and its hydrophobically-modified derivative (HM-HTCC) as potent inhibitors of the coronavirus HCoV-NL63. Here, we show that HTCC inhibits interaction of a virus with its receptor and thus blocks the entry. Further, we demonstrate that HTCC polymers with different degrees of substitution act as effective inhibitors of all low-pathogenic human coronaviruses.