Lassa fever

拉萨热
  • 文章类型: Journal Article
    这项研究旨在制定一个数学框架,以研究拉萨病毒如何在相反性别的人类中传播。在没有拉沙热的情况下,在平衡点分析模型的稳定性。使用现实生活中的数据评估模型的有效性,并估计确定基本再现数所需的所有参数。进行敏感性分析以查明显着影响感染传播的关键参数。模拟了阈值参数与基本再现数之间的相互作用。控制论被用来设计和评估策略,比如提高认识运动,提倡使用避孕套,并部署灭鼠剂以有效减少病毒传播的可能性。
    This study aims to formulate a mathematical framework to examine how the Lassa virus spreads in humans of opposite genders. The stability of the model is analyzed at an equilibrium point in the absence of the Lassa fever. The model\'s effectiveness is evaluated using real-life data, and all the parameters needed to determine the basic reproduction number are estimated. Sensitivity analysis is performed to pinpoint the crucial parameters significantly influencing the spread of the infection. The interaction between threshold parameters and the basic reproduction number is simulated. Control theory is employed to devise and evaluate strategies, such as awareness campaigns, advocating condom usage, and deploying rodenticides to reduce the possibility of virus transmission efficiently.
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  • 文章类型: Journal Article
    拉萨热是西非特有的人畜共患传染病,病死率高,据报道存活患者受到污名化。这项研究调查了拉沙热(LF)并发听力损失(HL)的幸存者之间的歧视。
    这项横断面定性研究使用了深入的访谈指南,从HL患者那里收集了有关其污名经历的信息。在获得知情同意后,于2022年1月至4月在乔斯大学教学医院由训练有素的采访者团队以豪萨语进行了采访。采访记录被转录并从豪萨翻译成英语。使用NVivo软件使用主题框架方法进行数据分析。
    大多数(73%)受访者是男性(n=11);27%是女性(n=4)。中位年龄为35岁(四分位距,16.5).一些拉萨热患者经历了耻辱和歧视(53%),包括在患病期间和患病后的家庭和社区支持的孤立和撤回。HL增加了污名,因为一些病人被其他社区成员贴上了“聋人”的标签,越来越多的人感到耻辱和贬值。HL影响了一些无法与家人和客户良好沟通的人的社会经济福祉,并限制了社交互动。引起疼痛和冷漠。LF的一些幸存者及其HL后遗症的受害者经历了双重污名化。当他们患有LF时,三分之一的受访者报告说,家庭和社区成员回避和孤立,他们撤回了对他们及其近亲的照顾和支持。这些形式的污名化使他们的关系紧张。
    有必要解决LF幸存者的污名化问题,这些幸存者通过一致的社区拥有的意识来提高他们的生活质量,并建立强大的社会支持系统来帮助预防。
    UNASSIGNED: Lassa fever is a zoonotic infectious disease endemic in West Africa with a high case-fatality rate and reported stigmatization of surviving patients. This study examines discrimination among survivors of Lassa fever (LF) complicated by hearing loss (HL).
    UNASSIGNED: This cross-sectional qualitative study used an in-depth interview guide to collect information from patients with HL about their experience of stigma. Interviews were conducted by a trained team of interviewers at the Jos University Teaching Hospital between January and April 2022 in Hausa language after informed consent was obtained. Recordings of the interviews were transcribed and translated from Hausa to English. Data analysis was conducted using NVivo software using a thematic framework approach.
    UNASSIGNED: Most (73%) respondents were male (n = 11); 27% were female (n = 4). The median age was 35 years (interquartile range, 16.5). Some Lassa fever patients experienced stigma and discrimination (53%) including isolation and withdrawal of family and community support during and after illness. HL increased stigma, as some patients were labeled \"deaf\" by other community members, increasing perceived stigma and devaluation. HL affected the socio-economic wellbeing of some who could not communicate well with their families and customers and constrained social interactions, evoking pain and apathy. Some survivors of LF and victims of its sequelae of HL experienced double stigmatization. While they were ill with LF, a third of respondents reported avoidance and isolation by family and community members who withdrew care and support both to them and their close family members. These forms of stigmatization strained their relationships.
    UNASSIGNED: There is a need to address stigma in LF survivors who develop HL through concerted community-owned awareness to improve their quality of life along with a robust social support system to aid prevention.
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  • 文章类型: Journal Article
    拉沙热是一种西非啮齿动物传播的病毒性出血热,每年杀死数千人,每年有100000至300000人可能感染拉沙病毒(LASV)。LASV的主要水库是纳塔尔多母鼠,纳塔尔人。据报道,啮齿动物种群中的感染高峰与人群中的拉沙热高峰风险之间存在异步性。可能是由于不同的季节性接触率。这里,我们在其啮齿动物宿主中开发了一种基于LASV动力学的易感感染恢复([公式:见正文])模型,纳塔尔根,持续感染的类别和季节性分娩,以测试未来由于气候和土地利用变化而对季节性分娩的影响。我们的模拟表明,啮齿动物出生时间和同步性的变化将改变病毒流行的高峰,改变人们的风险,病毒动力学主要在成年人中稳定,在年轻人中变化,而是感染更多的人。我们计算时间平均基本繁殖数,[公式:见正文],对于这种传染病系统,由于分娩而导致人口规模周期性变化,使用时间平均法和敏感性分析显示了四个关键参数:承载能力,成人死亡率,成年人之间的传播参数和额外的疾病诱导的死亡率对纳塔尔氏菌LASV的维持影响最大,由于人类活动和干预,承载能力和成人死亡率可能会发生变化。
    Lassa fever is a West African rodent-borne viral haemorrhagic fever that kills thousands of people a year, with 100 000 to 300 000 people a year probably infected by Lassa virus (LASV). The main reservoir of LASV is the Natal multimammate mouse, Mastomys natalensis. There is reported asynchrony between peak infection in the rodent population and peak Lassa fever risk among people, probably owing to differing seasonal contact rates. Here, we developed a susceptible-infected-recovered ([Formula: see text])-based model of LASV dynamics in its rodent host, M. natalensis, with a persistently infected class and seasonal birthing to test the impact of changes to seasonal birthing in the future owing to climate and land use change. Our simulations suggest shifting rodent birthing timing and synchrony will alter the peak of viral prevalence, changing risk to people, with viral dynamics mainly stable in adults and varying in the young, but with more infected individuals. We calculate the time-average basic reproductive number, [Formula: see text], for this infectious disease system with periodic changes to population sizes owing to birthing using a time-average method and with a sensitivity analysis show four key parameters: carrying capacity, adult mortality, the transmission parameter among adults and additional disease-induced mortality impact the maintenance of LASV in M. natalensis most, with carrying capacity and adult mortality potentially changeable owing to human activities and interventions.
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  • 文章类型: Letter
    利巴韦林安瓿制剂仍然是管理拉沙热疾病的主要挑战。拉沙热是西非次区域的地方性病毒性出血热,其中以高剂量利巴韦林为护理标准。所需的高剂量治疗使200mg/ml安瓿剂量的利巴韦林成为一项艰巨的任务,尤其是在疾病爆发期间。这篇评论强调了挑战,并热情地呼吁调整小瓶剂量以适应拉沙热疾病的高剂量要求。
    Ribavirin ampoule formulation remains a major challenge in managing Lassa fever disease. Lassa fever is an endemic viral hemorrhagic fever in the West Africa subregion, which has high-dose ribavirin as the standard of care. The high-dose therapy required makes the 200 mg/ml ampoule dosing of ribavirin a daunting task to administer, especially during disease outbreaks. This commentary highlights the challenges and makes a passionate call for vial dosage adjustment to fit the high-dose requirement of Lassa fever disease.
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  • 文章类型: Journal Article
    手部卫生被认为是防止微生物交叉传播和减少医疗保健相关感染发生率的主要措施。
    评估即使在拉沙热之后,牙科卫生工作者的卫生知识和实践。
    这项基于问卷调查的描述性横断面研究是在江户州的四家公立医院进行的。所有数据都是在获得伦理许可后使用自我管理的结构化问卷收集的。
    在分发的120份问卷中,有108份被填写并返回,回复率为90.0%。对受访者手部卫生知识的整体评估显示,41.7%的受访者具有良好的手部卫生知识,37.0%有优秀的知识,17.6%的中度和3.7%的手卫生知识薄弱。手卫生实践的总体评估显示,58.3%的受访者的手卫生实践是公平的,而37.0%的手卫生实践较差。只有少数(5.6%)的受访者有良好的手卫生习惯。
    拉沙热的爆发似乎并未对受访者的手卫生行为产生积极影响。虽然在这项研究中手卫生知识令人满意,这种做法仍然有很多不足之处。
    UNASSIGNED: Hand hygiene is recognized as the leading measure to prevent the cross-transmission of microorganisms and to reduce the incidence of healthcare-associated infections.
    UNASSIGNED: To assess the knowledge and practice of hygiene among dental health workers even in the wake of Lassa fever.
    UNASSIGNED: This questionnaire-based descriptive cross-sectional study was carried out in four public hospitals in Edo state. All data were collected using a self-administered structured questionnaire after obtaining ethical clearance.
    UNASSIGNED: 108 of the 120 questionnaires distributed were filled and returned giving a response rate of 90.0%. Overall assessment of respondents\' knowledge of hand hygiene revealed that 41.7% of the respondents possessed a good knowledge of hand hygiene, 37.0% had excellent knowledge, 17.6% had moderate and 3.7% had a weak knowledge of hand hygiene. Overall assessment of the practice of hand hygiene showed that the hand hygiene practice of 58.3% of respondents was fair while 37.0% practiced hand hygiene poorly. Only a few (5.6%) respondents had good hand hygiene practices.
    UNASSIGNED: The outbreak of Lassa fever does not seem to positively influence the practice of hand hygiene among the respondents. While knowledge of hand hygiene is satisfactory in this study, the practice still leaves much to be desired.
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    文章类型: Journal Article
    拉沙热是由拉沙病毒引起的病毒性出血性疾病,Arenavirus家族的单链RNA病毒。这是一种由Mastomysnatalensis的大鼠传播的人畜共患疾病。在第1周和第17周(2017年)之间,尼日利亚报告了242例疑似拉沙热病例,58例实验室确诊病例和46例死亡(CFR,19.01%)来自20个州的50个地方政府区域(LGA)。
    我们进行了疫情调查,并收集了索引病例和接触者的全面临床病史,然后使用标准的病毒性出血热接触监测表进行随访。在此之后,从该患者收集血液样本。总共跟踪了54名接触者21天,并使用临床温度计记录了他们的温度。此外,对Zabarmari社区和Madinatu境内流离失所者营地进行了环境评估。
    索引病例是一名32岁的妇女,她在Zabarmari社区内流离失所。她的症状始于发烧和阴道出血,然后进展为鼻出血,嘴,还有尿道.有老鼠暴露的历史以及环境卫生和个人卫生不足。实时荧光定量PCR检测血样中的拉沙热。博尔诺州环境部,与卫生部合作,开展了预防拉萨热的公共卫生教育,并采取了出色的卫生措施。
    提高对良好感染预防和控制措施的认识对于国内流离失所者和卫生保健提供者来说至关重要,以防止疾病的发生和传播。
    UNASSIGNED: Lassa fever is a viral hemorrhagic disease caused by the Lassa virus, a single stranded RNA virus of the Arenavirus family. It is a zoonotic illness spread by rats of the speciesMastomys natalensis . Between weeks 1 and 17, (2017), 242 suspected Lassa fever cases were reported in Nigeria, with 58 laboratory confirmed cases and 46 fatalities (CFR, 19.01%) from 50 Local Government Areas (LGAs) in 20 States.
    UNASSIGNED: We conducted an outbreak investigation and gathered a thorough clinical history of the index case as well as contacts, who were then followed up using the standard viral hemorrhagic fever contact monitoring form. Following that, blood samples were collected from this patient. A total of 54 contacts were tracked for 21 days and their temperatures were recorded using a clinical thermometer. Furthermore, an environmental evaluation of the Zabarmari community and the Madinatu Internally-displaced persons\' (IDP) camp was carried out.
    UNASSIGNED: The index case was a 32-year-old woman who was internallydisplaced in Zabarmari community. Her symptoms began with fever and vaginal bleeding and progressed to bleeding from the nose, mouth, and urethra. There was a history of rat exposure as well as inadequate environmental sanitation and hygiene. Real Time PCR detected Lassa fever in the blood sample. The Borno State Ministry of Environment, in partnership with the Ministry of Health, undertook public health education on Lassa fever prevention and implemented excellent sanitary measures.
    UNASSIGNED: Increased awareness creation on good infection prevention and control practices is crucial among internally-displaced person and health care providers to prevent occurrence and spread of the disease.
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  • 文章类型: Journal Article
    病毒性出血热(VHF)对人类健康构成重大威胁。近年来,由埃博拉病毒引起的VHF爆发,马尔堡病毒和拉萨病毒在西非和中非造成了大量的发病率和死亡率。2022年,由苏丹病毒引起的乌干达埃博拉疫情导致164例病例,55例死亡。2023年,在赤道几内亚和坦桑尼亚确认了马尔堡病爆发,导致超过49例确诊或疑似病例;其中41例是致命的。对这些VHF的防护没有明确的关联,阻碍靶向疫苗的发展。因此,所开发的任何疫苗应诱导针对这些病毒的强的和优选持久的体液和细胞免疫。理想情况下,这种免疫力也应该交叉保护免受病毒变异,已知在动物水库中循环并引起人类疾病。我们利用了两个病毒载体疫苗平台,腺病毒(ChAdOx1)和改良的安卡拉痘苗(MVA),开发针对三种丝状病毒(埃博拉病毒,苏丹病毒,马尔堡病毒)和沙粒病毒(拉沙病毒)。这些平台技术一直证明了在人类中诱导强大的细胞和体液抗原特异性免疫的能力。最近推出了许可的ChAdOx1-nCoV19/AZD1222。这里,我们证明我们的多病原体疫苗能引起强大的细胞和体液免疫,诱导不同范围的趋化因子和细胞因子,最重要的是,在致命的埃博拉病毒之后提供保护,苏丹病毒和马尔堡病毒在小动物模型中的挑战。
    Viral haemorrhagic fevers (VHF) pose a significant threat to human health. In recent years, VHF outbreaks caused by Ebola, Marburg and Lassa viruses have caused substantial morbidity and mortality in West and Central Africa. In 2022, an Ebola disease outbreak in Uganda caused by Sudan virus resulted in 164 cases with 55 deaths. In 2023, a Marburg disease outbreak was confirmed in Equatorial Guinea and Tanzania resulting in over 49 confirmed or suspected cases; 41 of which were fatal. There are no clearly defined correlates of protection against these VHF, impeding targeted vaccine development. Any vaccine developed should therefore induce strong and preferably long-lasting humoral and cellular immunity against these viruses. Ideally this immunity should also cross-protect against viral variants, which are known to circulate in animal reservoirs and cause human disease. We have utilized two viral vectored vaccine platforms, an adenovirus (ChAdOx1) and Modified Vaccinia Ankara (MVA), to develop a multi-pathogen vaccine regime against three filoviruses (Ebola virus, Sudan virus, Marburg virus) and an arenavirus (Lassa virus). These platform technologies have consistently demonstrated the capability to induce robust cellular and humoral antigen-specific immunity in humans, most recently in the rollout of the licensed ChAdOx1-nCoV19/AZD1222. Here, we show that our multi-pathogen vaccines elicit strong cellular and humoral immunity, induce a diverse range of chemokines and cytokines, and most importantly, confers protection after lethal Ebola virus, Sudan virus and Marburg virus challenges in a small animal model.
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  • 文章类型: Journal Article
    背景:拉沙热(LF)在塞拉利昂带来了重大的公共卫生挑战,尤其是在下班巴拉酋长领地。这项研究旨在深入了解对LF的知识和态度如何与社区驱动的预防和控制措施相关联。
    方法:采用描述性横断面定量方法进行研究。从2022年2月1日至2022年2月14日,使用基于Android的调查收集了2167名参与者的数据。受访者对LF原因的了解,危险因素,传输模式,通过多项选择问卷评估预防措施,对预防和控制的态度以5点李克特量表进行测量。定量数据使用SPSS26.0版进行分析,频率以计数表示,百分比,和桌子。卡方统计量用于检验关联。
    结果:在2167名参与者中,一半以上是男性(1184,54.60%),农民(1406,64.90%),已婚(一夫一妻制)(1428,65.90%),从未上过学(1336,61.70%)。受访者在社会人口统计学群体中表现出很高的LF知识水平(33%至100%),并对预防和控制持积极态度(5-40量表的平均得分为26.77)。教育水平,宗教信仰,职业状况对LF知识有显著影响(p<0.05)。具体来说,文盲的知识得分高达48.24%,而受过高等教育的人得分最高,为83.33%。此外,aPearson相关分析显示,对LF感染的知识程度和积极态度与死亡危险因素之间呈正线性关系(r=0.090,p=0.02).
    结论:下班巴拉酋长区的高LF知识对预防态度有积极影响。教育,宗教,职业是关键因素。量身定制的干预措施可增强公共卫生工作。
    BACKGROUND: Lassa fever (LF) presents significant public health challenges in Sierra Leone, particularly in the Lower Bambara Chiefdom. This study aims to deeply understand how knowledge and attitudes towards LF correlate with community-driven prevention and control measures.
    METHODS: A descriptive cross-sectional quantitative approach was used to conduct the research. Data from 2167 participants were collected using an Android-based survey from 1st February 2022 to 14th February 2022. Respondents\' knowledge of LF causes, risk factors, transmission modes, and preventive measures were evaluated through a multiple-choice questionnaire, and attitudes toward prevention and control were measured on a 5-point Likert scale. Quantitative data were analyzed using SPSS version 26.0 and frequencies were presented in count, percentage, and table. Chi-square statistics were used to test for associations.
    RESULTS: Among the 2167 participants, over half were males (1184, 54.60%), farmers (1406, 64.90%), married (monogamous) (1428, 65.90%), and had never attended school (1336, 61.70%). Respondents demonstrated high knowledge levels of LF across socio-demographic groups (33% to 100%) and shared a positive attitude towards prevention and control (mean score of 26.77 on a 5-40 scale). Educational level, religious beliefs, and occupational status significantly influenced LF knowledge (p < 0.05). Specifically, illiterates had a high knowledge score of 48.24%, while those with tertiary education had the highest score at 83.33%. Additionally, a Pearson correlation analysis revealed a positive linear relationship between the degree of knowledge and positive attitude towards LF infection and mortality risk factors (r = 0.090, p = 0.02).
    CONCLUSIONS: High LF knowledge in Lower Bambara Chiefdom positively influences prevention attitudes. Education, religion, and occupation are key factors. Tailored interventions enhance public health efforts.
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  • 文章类型: Journal Article
    拉沙热(LF),由拉沙病毒(LASV)引起,是对公众健康最危险的疾病之一。同源重组(HR)是驱动生物进化的基本遗传动力。然而,作为一种负链RNA病毒,尚不清楚LASV之间是否发生HR及其对LF爆发的影响。在这项研究中,在分析了在非洲收集的575S和433LLASV片段后,我们发现LASV可以在其两个细分市场中实现HR。有趣的是,虽然S段的长度小于L段的一半,具有S重组体的LASV的比例明显高于具有L重组体的LASV。这些结果表明HR可能是LASV的一个特征,可以通过自然选择来设定,以产生有益的或消除有害的病毒突变,因此在LF爆发期间在LASV进化中起作用。
    Lassa fever (LF), caused by Lassa virus (LASV), is one of the most dangerous diseases to public health. Homologous recombination (HR) is a basic genetic power driving biological evolution. However, as a negative-stranded RNA virus, it is unknown whether HR occurs between LASVs and its influence on the outbreak of LF. In this study, after analyzing 575 S and 433 L segments of LASV collected in Africa, we found that LASV can achieve HR in both of its segments. Interestingly, although the length of S segment is less than half of the L segment, the proportion of LASVs with S recombinants is significantly higher than that with L recombinants. These results suggest that HR may be a feature of LASV, which can be set by natural selection to produce beneficial or eliminate harmful mutations for the virus, so it plays a role in LASV evolution during the outbreak of LF.
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  • 文章类型: Journal Article
    拉沙病毒(LASV)是人类拉沙热的病原体,其在严重的情况下表现为每年导致数千人死亡的出血热。然而,目前尚无批准的疫苗或抗病毒药物。最近,我们使用表达LASV糖蛋白GP(VSV-LASVGP)的重组水泡性口炎病毒(VSV)筛选了约2,500种化合物,并鉴定了P-糖蛋白抑制剂为潜在的LASV进入抑制剂.这里,我们显示另一个确定的候选人,hexestrol(HES),雌激素受体激动剂,也是LASV进入抑制剂。HES以0.63μM的50%抑制浓度(IC50)抑制VSV-LASVGP复制。重要的是,HES还抑制真正的LASV复制,IC50值为0.31µM-0.61µM。添加时间和基于细胞的膜融合测定表明HES在病毒进入期间抑制膜融合步骤。替代雌激素受体激动剂不抑制VSV-LASVGP复制,这表明雌激素受体本身不太可能参与HES的抗病毒活性。HES抗性突变体的产生揭示了LASVGP氨基酸位置446(F446)的苯丙氨酸,它位于跨膜区域,赋予了对HES的抵抗力。尽管F446的突变增强了LASVGP的膜融合活性,它表现出减少的VSV-LASVGP复制,很可能是由于LASVGP融合前状态的不稳定性。总的来说,我们的结果表明,HES是一种有前景的抗LASV药物,其通过抑制LASV进入的膜融合步骤起作用.这项研究还强调了LASVGP跨膜区作为抗LASV药物靶标的重要性。IMPORTANCELassa病毒(LASV),拉沙热的病原体,就其对西非公共卫生的影响而言,是最具破坏性的哺乳动物病毒。然而,目前尚无批准的抗病毒药物或疫苗。这里,我们确定了hexestrol(HES),雌激素受体激动剂,作为潜在的抗病毒候选药物。我们表明,雌激素受体本身不参与抗病毒活性。HES直接与LASVGP结合并阻断膜融合,从而抑制LASV感染。通过产生抗HES病毒,我们发现LASVGP跨膜区446位(F446)的苯丙氨酸在HES的抗病毒活性中起着至关重要的作用。F446突变导致病毒复制减少,可能是由于LASVGP融合前状态的不稳定性。这些发现突出了HES作为开发靶向LASV的抗病毒化合物的有希望的候选物的潜力。
    Lassa virus (LASV) is the causative agent of human Lassa fever which in severe cases manifests as hemorrhagic fever leading to thousands of deaths annually. However, no approved vaccines or antiviral drugs are currently available. Recently, we screened approximately 2,500 compounds using a recombinant vesicular stomatitis virus (VSV) expressing LASV glycoprotein GP (VSV-LASVGP) and identified a P-glycoprotein inhibitor as a potential LASV entry inhibitor. Here, we show that another identified candidate, hexestrol (HES), an estrogen receptor agonist, is also a LASV entry inhibitor. HES inhibited VSV-LASVGP replication with a 50% inhibitory concentration (IC50) of 0.63 µM. Importantly, HES also inhibited authentic LASV replication with IC50 values of 0.31 µM-0.61 µM. Time-of-addition and cell-based membrane fusion assays suggested that HES inhibits the membrane fusion step during virus entry. Alternative estrogen receptor agonists did not inhibit VSV-LASVGP replication, suggesting that the estrogen receptor itself is unlikely to be involved in the antiviral activity of HES. Generation of a HES-resistant mutant revealed that the phenylalanine at amino acid position 446 (F446) of LASVGP, which is located in the transmembrane region, conferred resistance to HES. Although mutation of F446 enhanced the membrane fusion activity of LASVGP, it exhibited reduced VSV-LASVGP replication, most likely due to the instability of the pre-fusion state of LASVGP. Collectively, our results demonstrated that HES is a promising anti-LASV drug that acts by inhibiting the membrane fusion step of LASV entry. This study also highlights the importance of the LASVGP transmembrane region as a target for anti-LASV drugs.IMPORTANCELassa virus (LASV), the causative agent of Lassa fever, is the most devastating mammarenavirus with respect to its impact on public health in West Africa. However, no approved antiviral drugs or vaccines are currently available. Here, we identified hexestrol (HES), an estrogen receptor agonist, as the potential antiviral candidate drug. We showed that the estrogen receptor itself is not involved in the antiviral activity. HES directly bound to LASVGP and blocked membrane fusion, thereby inhibiting LASV infection. Through the generation of a HES-resistant virus, we found that phenylalanine at position 446 (F446) within the LASVGP transmembrane region plays a crucial role in the antiviral activity of HES. The mutation at F446 caused reduced virus replication, likely due to the instability of the pre-fusion state of LASVGP. These findings highlight the potential of HES as a promising candidate for the development of antiviral compounds targeting LASV.
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