虎杖抗登革熱病毒感染之活性探討

登革熱病毒由於其傳播快速與感染率的提升而成為嚴重的全球性威脅，並造成各國健康上與經濟上的負擔。其臨床症狀從輕微的發燒、前額及骨頭疼痛至嚴重的登革出血熱或休克症候群，目前尚無治療登革熱之臨床用藥，因此開發抗登革熱病毒藥物為迫切任務。虎杖為傳統生藥，廣泛分佈於全世界，且有悠久的藥用歷史，其療效包含治療各式發炎、毛囊癬、黃疸等。本研究室先前研究初步發現虎杖有抗登革熱病毒活性，故本研究選擇此生藥進行深入的抗病毒活性及機轉探討。本實驗分別選擇甲醇與乙醇兩種溶媒萃取虎杖根莖藥材，藉由細胞模式探討虎杖抗病毒效用，並針對登革熱病毒感染週期與早期病毒入侵進行機轉探討。結果顯示虎杖在無細胞毒性的劑量下具有潛在的抗登革熱病毒感染的作用；另外，針對登革熱病毒感染週期進行機轉研究得知其作用於病毒感染初期，相對的在病毒感染前後加藥則無明顯抑制效果，且進一步發現虎杖能在細胞外環境使病毒顆粒失去感染力及抑制病毒與細胞膜結合與融合。因此，本研究發現虎杖醇萃取物有潛在抗病毒入侵的藥理活性，值得更進一步評估作為抗登革熱病毒初期感染的藥物

關鍵字

登革熱病毒；虎杖；抗病毒藥物；病毒入侵

並列摘要

Dengue virus (DENV) infection causes a serious global threat due to its rapid spread and rise in incidence, imposing considerable health and economic burdens. DENV can cause a range of symptoms from mild dengue fever (DF), forehead ache, and bone pain to severe dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Currently, there is no approved antiviral agent against dengue infection, which necessitates prompt strategies to develop effective drugs. Polygonum cuspidatum Sieb. et Zucc. (Polygonum cuspidatum) (PC) is a traditional and popular crude medicinal herb widely distributing in the world and has been known for treatment of favus, inﬂammation, jaundice, hyperlipemia and scald. Our previous study has discovered that Polygonum cuspidatum has anti-DENV activity during drug screening. Thus, we chose the crude medicine for further research. Herein, rhizomes of PC were extracted using methanol (PCME) and ethanol (PCEE) and were examined for antiviral activity against DENV infection in vitro. The impacts of PCME and PCEE treatments on the DENV life cycle and the early viral entry steps were explored. Data indicated that both PCME and PCEE potently inhibited DENV infection without causing cytotoxicity. In addition, examination on the viral life cycle demonstrated that PCME and PCEE targeted the initial stages of infection while pre- and postinfection treatments had no effect. Speciﬁcally, PCME and PCEE could efﬁciently inactivate DENV free virus particles and block the viral attachment and entry/fusion events without influencing viral replication, egress, and cell-to-cell spread. Due to its potency against DENV entry, we suggest that the alcohol extracts from PC may be further evaluated as entry-specific antiviral candidates and explored for the management of DENV infection.