Optimization of Inhibitory Peptides Targeting Phosphoprotein of Rabies Virus

  • Yongzhong LuEmail author
  • Linyue Cheng
  • Jie Liu


Rabies is a serious zoonosis caused by rabies virus (RABV) of the genus Lyssavirus, and immunotherapy is now the only approved, effective method for post-exposure prophylaxis against rabies in humans, whereas an effective antiviral therapy is still unavailable if the central nervous system is invaded. Phosphoprotein (P) is known to play pivotal roles in the life cycle of RABV, and has been regarded as a prime target for inhibitors of viral replication. This study aimed to carry out intracellular administration of a kind of P-binding peptide for RABV inhibition. A group of reported P-binding peptides were focused on for activity improvement by quantitative structure–activity relationship (QSAR) method, and then were mediated by cell penetrating peptide (CPP) for intracellular activity evaluation. The QSAR models had good performance in reliability and predictability (R2 ≥ 0.852, Q2 ≥ 0.601, \({\text{Q}}_{\text{ext}}^{2}\) ≥ 0.595), and the peptide screened by partial least squares (PLS) QSAR model (R2 = 0.994, Q2 = 0.937, \({\text{Q}}_{\text{ext}}^{2}\) = 0.981) exhibited even higher antiviral activity when it was delivered into the cells by CPP. Above all, this study provided an effective way for development of peptide drug against RABV.


Cell penetrating peptides Descriptor Post-exposure prophylaxis QSAR Vaccination 



This work was supported by Shandong Provincial Natural Science Foundation, China (Grant No. ZR2016CM25). We thank Shimao Zhu (Shenzhen Weiguang Biological Products Co., Ltd., China) for his generous technical assistance and advice.

Author Contributions

LYZ designed the study and wrote the manuscript, CLY built the models, LJ checked and polished the manuscript. All authors read and approved the final manuscript.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

No human or animal subjects were involved in the experiments, so an ethical approval was not required.

Informed Consent

Informed consent was not required in this study.


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Shandong Provincial Key Laboratory of Biochemical EngineeringQingdao University of Science and TechnologyQingdaoChina

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