Luo Zhaochen, Tian Dayong, Zhou Ming, Xiao Wenjie, Zhang Yachun, Li Mingming, Sui Baokun, Wang Wei, Guan Huashi, Chen Huanchun, Fu Zhen F, Zhao Ling
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
Glycoscience and Glycoengineering Laboratory, School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong, 266100, China.
PLoS One. 2015 Oct 14;10(10):e0140586. doi: 10.1371/journal.pone.0140586. eCollection 2015.
Rabies, caused by rabies virus (RABV), is an acute, fatal encephalitic disease that affects many warm-blooded mammals. Currently, post-exposure prophylaxis regimens are effective for most rabies cases, but once the clinical signs of the disease appear, current treatment options become ineffective. Carrageenan has been reported as a potent inhibitor of many viruses. In this study, the λ-carrageenan (λ-CG) P32 was investigated for its potential role in inhibiting RABV infection. Our results show that P32 specifically inhibits the replication of several RABV strains but not vesicular stomatitis virus in multiple cell lines and shows low cytotoxicity. P32 mainly abrogated viral replication during the early stage of the post-adsorption period. Further studies demonstrated that P32 could affect not only viral internalization but also viral uncoating by blocking cell fusion mediated by RABV glycoprotein. Moreover, P32 can fully inhibit RABV infection in vitro during the post-adsorption period, whereas heparin and heparan sulfate, which possess similar structures to P32, showed significant but not complete inhibition of RABV infectivity. Collectively, our results indicate that λ-CG P32 is a promising agent that can inhibit RABV infection mainly by inhibiting viral internalization and glycoprotein-mediated cell fusion and can be used for the development of novel anti-RABV drugs.
狂犬病由狂犬病病毒（RABV）引起，是一种影响多种温血哺乳动物的急性致命性脑炎疾病。目前，暴露后预防方案对大多数狂犬病病例有效，但一旦疾病的临床症状出现，当前的治疗选择就会失效。角叉菜胶已被报道为多种病毒的有效抑制剂。在本研究中，对λ-角叉菜胶（λ-CG）P32抑制RABV感染的潜在作用进行了研究。我们的结果表明，P32在多种细胞系中特异性抑制几种RABV毒株的复制，但不抑制水疱性口炎病毒，且细胞毒性较低。P32主要在吸附后早期阶段消除病毒复制。进一步研究表明，P32不仅可以影响病毒内化，还可以通过阻断RABV糖蛋白介导的细胞融合来影响病毒脱壳。此外，P32在吸附后阶段可在体外完全抑制RABV感染，而与P32结构相似的肝素和硫酸乙酰肝素对RABV感染性有显著但不完全的抑制作用。总体而言，我们的结果表明，λ-CG P32是一种有前景的药物，它主要通过抑制病毒内化和糖蛋白介导的细胞融合来抑制RABV感染，可用于开发新型抗RABV药物。
