Targeting the alphavirus virus replication process for antiviral development

• Main Authors: Tan, Yaw Bia, Law, Michelle Cheok Yien, Luo, Dahai
• Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
• Format: Article
• Language: English
• Published: 2023
• Subjects: Science::Medicine; Science::Biological sciences; Alphavirus; Replication Complex
• Online Access: https://hdl.handle.net/10356/168999
• Institution: Nanyang Technological University

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.