It must be taken into account that

It must be taken into account that the compounds may also interact with the flexible N-terminal domain because NPRs have been derived by molecular simulation from human PrP (124–230 a.a.). To address this point, an in vitro-binding experiment (i.e. SPR) with purified PrPs (121–231 and 90–231 a.a.) will be needed. In addition, interaction with abnormal form is also another possible action of anti-prion drugs and we cannot exclude this possibility regarding with the NPRs. Continuously, conformation of fibril formed PrP has been analysed using solid-state NMR, X-ray fiber diffraction, Hydrogen exchange mass spectrometry or AS 2034178 micrograph with high resolution (Laws et al., 2001; Helmus et al., 2008; Wille et al., 2009; Damo et al., 2010; Smirnovas et al., 2011), thereby high content of beta sheet and their stacking structure were suggested (Wille et al., 2002; Groveman et al., 2014). However, there are still some obligations to overcome before using the structural information in docking simulation on DEGIMA at present, because some of them are hypothetical and not sufficient. In the future, specific anti-prion drugs that can directly interact with abnormal PrP structure will be necessary for treatment of prion disease, because normal cellular PrP has a critical physiological function on maintenance of myelin and axon (Bremer et al., 2010). In conclusion, results from in silico screening and targeting of the PrPC structure showed that this method could be useful for drug discovery against prion disease. Future studies should evaluate these effects in animal models of disease, in in vitro screening with post-translational modifications of PrPC and in the structure analysis using NMR of the compounds–PrPC complexes. Results also showed that NPRs could be made widely available as candidate drugs for conformational disease.
Competing interests
Author contribution statement
Acknowledgments We thank Dr. Yoshimasa Tanaka and Prof. Katsuya Satoh from Nagasaki University and Dr. Yuji O. Kamatari from Gifu University for helpful discussions and critical assessment of the manuscript, and Hanako Nakayama, Ayako Nakazaki, Atsuko Matsuo and Megumi Tanaka for technical assistance. This work was supported by a Grant-in-Aid of the Research Committee of Prion Disease and Slow Virus Infection from the Ministry of Health, Labor and Welfare of Japan; a Grant-in-Aid of the Research Committee of Molecular Pathogenesis and Therapies for Prion Disease and Slow Virus Infection, the Practical Research Project for Rare and Intractable Disease from the Japan Agency for Medical Research and Development, AMED; a grant from the Takeda Science Foundation; a grant from the Japan Intractable Disease Research Foundation; a Grant-in-Aid from the Tokyo Biochemical Research Foundation; and a grant provided by the YOKOYAMA Foundation for Clinical Pharmacology (Grant No. YRY1502).
Introduction On May 17th, 2015, the Program for Monitoring Emerging Diseases (ProMED-mail) published a report confirming locally acquired cases of Zika virus (ZIKV) in several northeastern Brazilian states, marking the first time this virus is known to have spread within the Americas (Promed, 2015). Eight months later, on February 1st, 2016 the World Health Organization declared the ZIKV epidemic in the Americas a Public Health Emergency of International Concern, in part due to an emerging association with congenital birth anomalies such as microcephaly (Calvet et al., 2016; Mlakar et al., 2016; Rodrigues, 2016) and Guillain-Barré syndrome (Cao-Lormeau et al., 2016). After the virus\' introduction into Brazil, the epidemic has swiftly spread across Latin America and the Caribbean (Faria et al., 2016; Petersen et al., 2016a). Potential reasons for this rapid spread include the presence of immunologically naïve populations and an abundance of Aedes mosquitoes (Kraemer et al., 2015) within a conducive environment.