Antiviral Research ( IF 4.5 ) Pub Date : 2022-12-24 , DOI: 10.1016/j.antiviral.2022.105494 Yaw Bia Tan 1 , Michelle Cheok Yien Law 1 , Dahai Luo 1
Many alphaviruses, including chikungunya virus (CHIKV) are known human pathogens that lack specific and effective antivirals or vaccines available. The upstream portion of the positive-sense single-stranded RNA genome of alphaviruses encodes four nonstructural proteins: nsP1 to nsP4. They are expressed and autoprocessed to nonstructural proteins which assemble into a replication complex (RC) playing multiple essential roles on viral RNA replication and communication with the host components. The assembly of alphavirus RC and its RNA genome initiates the membrane-derived ultrastructure known as spherule which facilitates viral RNA synthesis protected from host immune responses. Recent advances in the molecular understanding of the high-resolution CHIKV RC heteromeric ultrastructure have provided new insights into the viral replication process. Hence, alphavirus RC presents as an ideal multi-enzyme target for the development of structure-based antiviral drugs. Moreover, the alphavirus RC has therapeutic potential in the form of self-amplifying RNA technology against both infectious and non-infectious diseases.
中文翻译:
针对甲病毒复制过程进行抗病毒开发
许多甲病毒,包括基孔肯雅病毒 (CHIKV),是已知的人类病原体,缺乏特异性和有效的抗病毒药物或疫苗。甲病毒的正义单链 RNA 基因组的上游部分编码四种非结构蛋白:nsP1 到 nsP4。它们被表达并自动加工成非结构蛋白,这些蛋白组装成复制复合物 (RC),在病毒 RNA 复制和与宿主成分的通讯中发挥着多种重要作用。甲病毒 RC 及其 RNA 基因组的组装启动了称为小球的膜衍生超微结构,它促进了病毒 RNA 的合成,使其免受宿主免疫反应的影响。对高分辨率 CHIKV RC 异聚超微结构的分子理解的最新进展为病毒复制过程提供了新的见解。因此,甲病毒 RC 是开发基于结构的抗病毒药物的理想多酶靶标。此外,甲病毒 RC 以自我扩增 RNA 技术的形式具有治疗传染性和非传染性疾病的潜力。