Targeting the alphavirus virus replication process for antiviral development
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 expres...
| Main Authors: | , , |
|---|---|
| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2023
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/168999 |
| _version_ | 1811690897072455680 |
|---|---|
| author | Tan, Yaw Bia Law, Michelle Cheok Yien Luo, Dahai |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Tan, Yaw Bia Law, Michelle Cheok Yien Luo, Dahai |
| author_sort | Tan, Yaw Bia |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T06:11:17Z |
| format | Journal Article |
| id | ntu-10356/168999 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:11:17Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | ntu-10356/1689992023-06-26T07:27:59Z Targeting the alphavirus virus replication process for antiviral development Tan, Yaw Bia Law, Michelle Cheok Yien Luo, Dahai Lee Kong Chian School of Medicine (LKCMedicine) NTU Institute of Structural Biology Science::Medicine Science::Biological sciences Alphavirus Replication Complex 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. Ministry of Education (MOE) This research is supported by the Singapore Ministry of Education under its MOE AcRF Tier 2 Award [grant number MOE-T2EP30220- 0009] and MOE AcRF Tier 1 Award [grant number 2021-T1-002-021], awarded to D.L. 2023-06-26T07:27:58Z 2023-06-26T07:27:58Z 2023 Journal Article Tan, Y. B., Law, M. C. Y. & Luo, D. (2023). Targeting the alphavirus virus replication process for antiviral development. Antiviral Research, 210, 105494-. https://dx.doi.org/10.1016/j.antiviral.2022.105494 0166-3542 https://hdl.handle.net/10356/168999 10.1016/j.antiviral.2022.105494 210 2-s2.0-85145693028 210 105494 en MOE-T2EP30220- 0009 2021-T1-002-021 Antiviral Research © 2022 Elsevier B.V. All rights reserved. |
| spellingShingle | Science::Medicine Science::Biological sciences Alphavirus Replication Complex Tan, Yaw Bia Law, Michelle Cheok Yien Luo, Dahai Targeting the alphavirus virus replication process for antiviral development |
| title | Targeting the alphavirus virus replication process for antiviral development |
| title_full | Targeting the alphavirus virus replication process for antiviral development |
| title_fullStr | Targeting the alphavirus virus replication process for antiviral development |
| title_full_unstemmed | Targeting the alphavirus virus replication process for antiviral development |
| title_short | Targeting the alphavirus virus replication process for antiviral development |
| title_sort | targeting the alphavirus virus replication process for antiviral development |
| topic | Science::Medicine Science::Biological sciences Alphavirus Replication Complex |
| url | https://hdl.handle.net/10356/168999 |
| work_keys_str_mv | AT tanyawbia targetingthealphavirusvirusreplicationprocessforantiviraldevelopment AT lawmichellecheokyien targetingthealphavirusvirusreplicationprocessforantiviraldevelopment AT luodahai targetingthealphavirusvirusreplicationprocessforantiviraldevelopment |