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-Structure paper
タイトル | Structure of the Spring Viraemia of Carp Virus Ribonucleoprotein Complex Reveals Its Assembly Mechanism and Application in Antiviral Drug Screening. |
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ジャーナル・号・ページ | J Virol, Vol. 97, Issue 4, Page e0182922, Year 2023 |
掲載日 | 2023年4月27日 |
著者 | Zhao-Xi Wang / Bing Liu / Tian Yang / Daqi Yu / Chu Zhang / Liming Zheng / Jin Xie / Bin Liu / Mengxi Liu / Hailin Peng / Luhua Lai / Qi Ouyang / Songying Ouyang / Yong-An Zhang / |
PubMed 要旨 | Spring viremia of carp virus (SVCV) is a highly pathogenic infecting the common carp, yet neither a vaccine nor effective therapies are available to treat spring viremia of carp (SVC). Like all ...Spring viremia of carp virus (SVCV) is a highly pathogenic infecting the common carp, yet neither a vaccine nor effective therapies are available to treat spring viremia of carp (SVC). Like all negative-sense viruses, SVCV contains an RNA genome that is encapsidated by the nucleoprotein (N) in the form of a ribonucleoprotein (RNP) complex, which serves as the template for viral replication and transcription. Here, the three-dimensional (3D) structure of SVCV RNP was resolved through cryo-electron microscopy (cryo-EM) at a resolution of 3.7 Å. RNP assembly was stabilized by N and C loops; RNA was wrapped in the groove between the N and C lobes with 9 nt nucleotide per protomer. Combined with mutational analysis, our results elucidated the mechanism of RNP formation. The RNA binding groove of SVCV N was used as a target for drug virtual screening, and it was found suramin had a good antiviral effect. This study provided insights into RNP assembly, and anti-SVCV drug screening was performed on the basis of this structure, providing a theoretical basis and efficient drug screening method for the prevention and treatment of SVC. Aquaculture accounts for about 70% of global aquatic products, and viral diseases severely harm the development of aquaculture industry. Spring viremia of carp virus (SVCV) is the pathogen causing highly contagious spring viremia of carp (SVC) disease in cyprinids, especially common carp (), yet neither a vaccine nor effective therapies are available to treat this disease. In this study, we have elucidated the mechanism of SVCV ribonucleoprotein complex (RNP) formation by resolving the 3D structure of SVCV RNP and screened antiviral drugs based on the structure. It is found that suramin could competitively bind to the RNA binding groove and has good antiviral effects both and . Our study provides a template for rational drug discovery efforts to treat and prevent SVCV infections. |
リンク | J Virol / PubMed:36943056 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 3.7 - 3.98 Å |
構造データ | EMDB-33810, PDB-7yg7: PDB-7xpn: |
由来 |
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キーワード | VIRAL PROTEIN / SVCV / RNP / VIRUS / VIRUS LIKE PARTICLE/RNA / Ribonucleoprotein / Complex / VIRUS LIKE PARTICLE-RNA complex |