Protein Structure-Function and Research Unit, School of Molecular and Cell Biology, Faculty of Science, University of the Witwatersrand, Braamfontein, Johannesburg 2050, South Africa.
Department of Medical Biochemistry, Alex Ekwueme Federal University Ndufu-Alike, Abakaliki PMB 1010, Ebonyi State, Nigeria.
Viruses. 2023 Jan 3;15(1):146. doi: 10.3390/v15010146.
Lassa fever (LF) is a rodent-borne disease that threatens human health in the sub-region of West Africa where the zoonotic host of Lassa virus (LASV) is predominant. Currently, treatment options for LF are limited and since no preventive vaccine is approved for its infectivity, there is a high mortality rate in endemic areas. This narrative review explores the transmission, pathogenicity of LASV, advances, and challenges of different treatment options. Our findings indicate that genetic diversity among the different strains of LASV and their ability to circumvent the immune system poses a critical challenge to the development of LASV vaccines/therapeutics. Thus, understanding the biochemistry, physiology and genetic polymorphism of LASV, mechanism of evading host immunity are essential for development of effective LASV vaccines/therapeutics to combat this lethal viral disease. The LASV nucleoprotein (NP) is a novel target for therapeutics as it functions significantly in several aspects of the viral life cycle. Consequently, LASV NP inhibitors could be employed as effective therapeutics as they will potentially inhibit LASV replication. Effective preventive control measures, vaccine development, target validation, and repurposing of existing drugs, such as ribavirin, using activity or in silico-based and computational bioinformatics, would aid in the development of novel drugs for LF management.
拉沙热(LF)是一种啮齿动物传播的疾病,在拉沙病毒(LASV)的人畜共患病宿主占主导地位的西非次区域威胁着人类健康。目前,LF 的治疗选择有限,由于没有针对其传染性的预防性疫苗获得批准,因此在流行地区的死亡率很高。本叙述性评论探讨了 LASV 的传播、致病性、不同治疗选择的进展和挑战。我们的研究结果表明,LASV 不同毒株之间的遗传多样性及其规避免疫系统的能力对 LASV 疫苗/疗法的开发构成了重大挑战。因此,了解 LASV 的生物化学、生理学和遗传多态性、逃避宿主免疫的机制对于开发有效的 LASV 疫苗/疗法来对抗这种致命的病毒性疾病至关重要。LASV 核蛋白(NP)是一种新的治疗靶点,因为它在病毒生命周期的几个方面都有重要作用。因此,LASV NP 抑制剂可以作为有效的治疗药物,因为它们可能会抑制 LASV 的复制。有效的预防控制措施、疫苗开发、靶点验证以及使用基于活性或基于计算机的生物信息学对现有药物(如利巴韦林)的重新利用,将有助于开发用于 LF 管理的新型药物。