探討藥用植物對登革熱病毒2型（DENV-2）NS3解旋酶結構域ATPase活性的抑製效果之研究

Abstract

登革熱病毒感染是由蚊子，主要品種爲埃及伊蚊和較小程度上的白紋伊蚊在人與人之間傳播的全身性感染。登革熱病毒共有四种血清型（登革熱病毒1型，登革熱病毒2型，登革熱病毒3型，登革熱病毒4型）;每种血清型登革病毒都能引發因人而異的全方位臨床表現，從無症狀感染到登革熱（DF）以及最嚴重的登革出血熱（DHF）和登革熱休克綜合徵（DSS）。登革熱病毒是屬於黃病毒科的黃病毒屬之成員; 在此屬科中也包含了其它幾個對公眾健康構成威脅的病毒。登革病毒是正義單鏈核糖核酸（ssRNA）病毒，其基因組擁有有約11000個核苷酸，編碼至少10種病毒蛋白，包括3結構蛋白和7個非結構（NS）蛋白。 NS3蛋白的C-末端結構域被稱為NS3解旋酶; NS3解旋酶結構域也有一個NTPase的活性，負責ATP水解以提供化學能量驅動RNA易位和解旋的機械過程。登革熱迅速擴大的足跡是一個當前未有特定的治療藥物或有效的病媒控制策略可以克服的全球性公共衛生挑戰與經濟負擔。開發登革熱病毒疫苗的過程中遇到的相關挑戰更凸顯了開發抗登革病毒藥物的重要性。此項研究篩選16藥用植物以評估這些植物對DENV-2 NS3解旋酶結構域ATPase活性的抑製劑開發的可能性。共有2種來自於Polygonum chinense植物的萃取物在篩選過程中表現出對DENV-2 NS3解旋酶結構域ATPase活性有一定程度的抑製；這2種萃取物已通過進行劑量反應試驗以進一步試驗它們對ATPase活性的抑製能力。Polygonum chinense乙酸乙酯萃取物對DENV-2 NS3解旋ATPase活性的抑製作用表現出對劑量的依賴性。

Dengue virus (DENV) infection is a systemic infection transmitted between humans by mosquitoes, mainly the species Aedes aegypti and, to lesser extent Aedes albopictus. There are total four serotypes of DENV (DENV-1, DENV-2, DENV-3 and DENV-4); each of these four serotypes of DENV is capable of causing the full spectrum of clinical manifestations that may varies from patient to patient, ranging from an asymptomatic infection to dengue fever (DF) and the most severe disease, dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS). The DENV are members of the Flavivirus genus of the Flaviviridae family; which includes in the same family are several viruses that pose a threat to public health. DENV is a positive-sense single-stranded RNA (ssRNA) virus with a genome of about 11 000 nucleotides which encodes at least 10 viral proteins including 3 structural proteins and 7 non-structural (NS) proteins. The C-terminal domain of the NS3 protein is known as NS3 helicase; NS3 helicase domain also has a nucleoside 5’-triphosphatase (NTPase) activity that responsible for ATP hydrolysis to provide the chemical energy to driven the translocation and unwinding mechanical process. The rapidly expanding footmark of dengue is a global public health challenge with an economic burden that is currently unmet by specific therapeutic agents or efficient vector control strategies. The challenges associated with the development of a successful DENV vaccine underlines the importance of antiviral development for DENV. Current study screened through 16 medicinal herbs to evaluate the possibilities of discovery of any inhibitors on the DENV-2 NS3 helicase ATPase activity. Total of 2 extracts of Polygonum chinense exhibited a certain degree of inhibition on the DENV-2 NS3 helicase ATPase activity in the plant extract screening section; these 2 extracts were further validated by conducting the dose response test. Ethyl acetate extract of Polygonum chinense exhibited inhibitory effects against the DENV-2 NS3 helicase ATPase activity in a dose-dependent manner.