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离子载体抗生素抑制体外 II 型猫冠状病毒的增殖。

Ionophore Antibiotics Inhibit Type II Feline Coronavirus Proliferation In Vitro.

机构信息

Department of Veterinary Hygiene, Veterinary School, Nippon Veterinary & Life Science University, 1-7-1 Kyounan, Musashino 180-8602, Japan.

Research Center for Animal Life Science, Nippon Veterinary & Life Science University, 1-7-1 Kyounan, Musashino 180-8602, Japan.

出版信息

Viruses. 2022 Aug 6;14(8):1734. doi: 10.3390/v14081734.

Abstract

Feline coronaviruses (FCoVs) infect cats worldwide and cause severe systemic diseases, such as feline infectious peritonitis (FIP). FIP has a high mortality rate, and drugs approved by the Food and Drug Administration have been ineffective for the treatment of FIP. Investigating host factors and the functions required for FCoV replication is necessary to develop effective drugs for the treatment of FIP. FCoV utilizes an endosomal trafficking system for cellular entry after binding between the viral spike (S) protein and its receptor. The cellular enzymes that cleave the S protein of FCoV to release the viral genome into the cytosol require an acidic pH optimized in the endosomes by regulating cellular ion concentrations. Ionophore antibiotics are compounds that form complexes with alkali ions to alter the endosomal pH conditions. This study shows that ionophore antibiotics, including valinomycin, salinomycin, and nigericin, inhibit FCoV proliferation in vitro in a dose-dependent manner. These results suggest that ionophore antibiotics should be investigated further as potential broad-spectrum anti-FCoV agents.

摘要

猫冠状病毒(FCoV)在全球范围内感染猫科动物,并导致严重的全身性疾病,如猫传染性腹膜炎(FIP)。FIP 的死亡率很高,而美国食品和药物管理局批准的药物对 FIP 的治疗无效。研究宿主因素和 FCoV 复制所需的功能对于开发治疗 FIP 的有效药物是必要的。FCoV 在与病毒刺突(S)蛋白与其受体结合后,利用内体运输系统进入细胞。将 FCoV 的 S 蛋白切割释放病毒基因组进入细胞质所需的细胞酶需要内体中通过调节细胞离子浓度优化的酸性 pH。离子载体抗生素是与碱金属离子形成复合物以改变内体 pH 条件的化合物。本研究表明,离子载体抗生素,包括缬氨霉素、盐霉素和 Nigericin,以剂量依赖的方式在体外抑制 FCoV 的增殖。这些结果表明,离子载体抗生素应该作为潜在的广谱抗 FCoV 药物进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e84/9415497/f2d59417ed91/viruses-14-01734-g001.jpg

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