The highly conserved RNA-binding specificity of nucleocapsid protein facilitates the identification of drugs with broad anti-coronavirus activity

The binding of SARS-CoV-2 nucleocapsid (N) protein to both the 5'- and 3'-ends of genomic RNA has different implications arising from its binding to the central region during virion assembly. However, the mechanism underlying selective binding remains unknown. Herein, we performed the high-throughput RNA-SELEX (HTR-SELEX) to determine the RNA-binding specificity of the N proteins of various SARS-CoV-2 variants as well as other {beta}-coronaviruses and showed that N proteins could bind two unrelated sequences, both of which were highly conserved across all variants and species. Interestingly, both these sequence motifs are virtually absent from the human transcriptome; however, they exhibit a highly enriched, mutually complementary distribution in the coronavirus genome, highlighting their varied functions in genome packaging. Our results provide mechanistic insights into viral genome packaging, thereby increasing the feasibility of developing drugs with broad-spectrum anti-coronavirus activity by targeting RNA binding by N proteins.

Application value of volumetric modulated arc therapy combined with zoledronic acid in treatment of vertebral metastasis / 肿瘤研究与临床

Objective To investigate the application value of volumetric modulated arc therapy (VMAT) combined with zoledronic acid in treatment of vertebral metastases. Methods A total of 58 patients with vertebral metastasis in Qingdao Central Hospital from January 2015 to June 2017 were extracted according to simple random sampling method. The data of 58 patients were analyzed retrospectively, and they were divided into 2 groups according to the different radiotherapy technology. The study group (28 cases) received VMAT combined with zoledronic acid treatment, and the control group (30 cases) received general radiotherapy combined with zoledronic acid treatment. The efficacy and tissue damage of the patients in both groups were compared according to the evaluation criterion including the local control rate, pain relief rate, local progression-free survival rate and exposure of the spinal cord. Results The local control rates were 92.9 ％ (26/28) and 73.3 ％ (22/30) respectively in the study group and the control group (χ2= 3.869, P=0.049). The pain relief rates were 96.4 ％ (27/28) and 76.7 ％ (23/30) respectively (χ2= 4.757, P= 0.029). The local progression-free survival rates of 3-month were 85.7 ％ (24/28), 60.0 ％ (18/30) respectively (χ2=4.794, P= 0.029) and the local progression-free survival rates of 6-month were 78.6 ％ (22/28), 50.0 ％(15/30) in the study group and the control group (χ2=5.119, P=0.024). The exposure of the spinal cord was (29.80±0.88) Gy and (39.90±0.20) Gy, respectively (t= -61.083, P= 0.000). Conclusion VMAT combined with zoledronic acid can improve the local control rate, pain relief rate, local progression-free survival rate, and reduce the exposure of the spinal cord.