Spring
viremia of carp virus (SVCV) is a highly pathogenic Vesiculovirus 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. IMPORTANCE 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 (Cyprinus carpio), 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 in vivo and in vitro. Our study provides a template for rational drug discovery efforts to treat and prevent SVCV
infections.