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Received by Michelle ID No.APJTB-2014-0566 Pages: Received on Revised on 2014-10-28 Scytovirin and Ebola virus glycoprotein: possible antiviral drug property approved by molecular docking study 氨基酸抗病毒蛋白和埃博拉病毒糖蛋白：潜在抗病毒性能 Abstract Ebola virus infection is the present global problem with the trend of worldwide pandemic. Searching for the new antiviral drug is the hope for management of the infection. Of several potential drug candidates, scytovirin is an interesting biomolecule. The antiviral activity of scytovirin towards Ebola virus glycoprotein is previously reported. However, there is still no clarification on the possible molecular interaction between scytovirin and Ebola virus glycoprotein. Here, the author use the standard molecular docking technique for identifying possible interaction and complex formation between scytovirin and Ebola virus glycoprotein. According to this study, the possible complex due to interaction between both molecules can be derived. This can be the clue on the antiviral biological process of scytovirin which might be useful for further drug development research. Key words: Ebola, glycoprotein, scytovirin Introduction Ebola virus infection is the present global problem with the trend of worldwide pandemic. Now (October 2014) more than ten thousands cases of Ebola infections are estimated and the disease control is still unsuccessful . The problem becomes more serious and the global pandemic is of great concerned . To stop the outbreak is still hopeless due to the lack of effective drug and vaccine. Searching for the new antiviral drug is the hope for management of the infection. There are many ongoing researches on finding of new antiviral drugs against Ebola virus . Of several potential drug candidates, scytovirin is an interesting biomolecule. The antiviral activity of scytovirin towards Ebola virus glycoprotein is previously reported . Garrison et al. proposed that “cyanobacterial lectin scytovirin (SVN) binds with high affinity to mannose-rich oligosaccharides on the envelope glycoprotein (GP) of a number of viruses, blocking entry into target cells ” and further found that the scytovirin was effective in management of Ebola virus infection in mice model. However, there is still no clarification on the possible molecular interaction between scytovirin and Ebola virus glycoprotein. Here, the author use the standard molecular docking technique for identifying possible interaction and complex formation between scytovirin and Ebola virus glycoprotein. According to this study, the possible complex due to interaction between both molecules can be derived. This can be the clue on the antiviral biological process of scytovirin which might be useful for further drug development research. Materials and methods This work is a molecular docking study. The standard technique as previously reported by Wiwanitkit is used . The primary templates for scytovirin (PDB: 2QT4_A) and Ebola virus glycoprotein (Zaire Ebola virus) (GenBank: AAB81004.1) was obtained from PubMed Database. First, the transformation of the primary template data into the sequence was done (Figure 1). The standard molecular docking tool provided by Vasker bioinformatics group was used for molecular docking study . The technique namely “GRAMM-X ” was used. This tool “is specifically designed for molecular docking pairs of protein molecules and ignores any small ligands or non-protein molecules” . Results According to the molecular docking study, the interaction between between scytovirin and Ebola virus glycoprotein is approved for possibility. The interaction can result in complex formation. The derived docked complex is shown in Figure 2. Discussion To test the possibility that a new antiviral drug candidate can be effectively interact with the virus is the basic step in new drug search. This is also the clue for success in drug search for fighting Ebola virus outbreak. To clarify the interaction requires a) approval of existed interaction and b) finding the resulted complex formation between drug candidate and virus. Here, the mentioned process is studied for the new candidate, scytovirin. Basically, scytovirin is widely mentioned for antiviral activity. In addition to anti – Ebola virus activitiy , its anti – HIV property is also mentioned [8 - 9]. The antiviral activity of scytovirin is believed to be due to its possible interaction to the virus glycoprotein and the mentioned interaction is believed to effectively preventing the viral entry to infect cell . In the present study, scytovirin is tested for the antiviral property towards Ebola virus. The standard molecular docking test was performed and it found that the interaction between scytovirin and Ebola virus glycoprotein was possible. In addition, the resulted complex is derived. This can approve that scytovirin can be a good antiviral drug candidate that should be further studied in human infected cases in the present Ebola virus infection outbreak. In addition, the basic properties of the derived complex will be further studied and reported. References 1. Brown CS, Cropley IM. Ebola virus disease: where are we now and where do we go? Postgrad Med J. 2014 Nov;90(1069):610-2. 2. Nau JY. Is the World Health Organization guilty of delaying the fight against Ebola?. Rev Med Suisse. 2014 Sep 3;10(440):1634-5. 3. Gulland A. Ebola drug trial is to start next month. BMJ. 2014 Oct 23;349:g6436. 4. Garrison AR, Giomarelli BG, Lear-Rooney CM, Saucedo CJ, Yellayi S, Krumpe LR, Rose M, Paragas J, Bray M, Olinger GG Jr, McMahon JB, Huggins J, O'Keefe BR. The cyanobacterial lectin scytovirin displays potent in vitro and in vivo activity against Zaire Ebola virus. Antiviral Res. 2014 Oct 5;112C:1-7. 5. Wiwanitkit V. Structure of human BRCA2-RAD51 by molecular docking study. Arch Gynecol Obstet. 2007 Dec;276(6):625-7. 6. Vakser IA, Kundrotas P. Predicting 3D structures of protein-protein complexes. Curr Pharm Biotechnol. 2008 Apr;9(2):57-66 7. Tovchigrechko A, Vakser IA. GRAMM-X public web server for protein-protein docking. Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W310-4. 8. Xiong C, O'Keefe BR, Byrd RA, McMahon JB. Potent anti-HIV activity of scytovirin domain 1 peptide. Peptides. 2006 Jul;27(7):1668-75. 9. Huskens D, Schols D. Algal lectins as potential HIV microbicide candidates. Mar Drugs. 2012 Jul;10(7):1476-97. 10. Jensen SM, Ruscetti FW, Rein A, Bertolette DC, Saucedo CJ, O'Keefe BR, Jones KS. Differential inhibitory effects of cyanovirin-N, griffithsin, and scytovirin on entry mediated by envelopes of gammaretroviruses and deltaretroviruses. J Virol. 2014 Feb;88(4):2327-32. Figure 1. Sequence of the primary templates A. Ebola virus glycoprotein MGVTGILQLPRDRFKRTSFFLWVIILFQRTFSIPLGVIHNSTLQVSDVDKLVCRDKLSS TNQLRSVGLNLEGNGVATDVPSATKRWGFRSGVPPKVVNYEAGEWAENCYNLEIK KPDGSECLPAAPDGIRGFPRCRYVHKVSGTGPCAGDFAFHKEGAFFLYDRLASTVIY RGTTFAEGVVAFLILPQAKKDFFSSHPLREPVNATEDPSSGYYSTTIRYQATGFGTNE TEYLFEVDNLTYVQLESRFTPQFLLQLNETIYTSGKRSNTTGKLIWKVNPEIDTTIGEW AFWETKKNLTRKIRSEELSFTVVSNGAKNISGQSPARTSSDPGTNTTTEDHKIMASEN SSAMVQVHSQGREAAVSHLTTLATISTSPQSLTTKPGPDNSTHNTPVYKLDISEATQV EQHHRRTDNDSTASDTPSATTAAGPPKAENTNTSKSTDFLDPATTTSPQNHSETAGN NNTHHQDTGEESASSGKLGLITNTIAGVAGLITGGRRTRREAIVNAQPKCNPNLHYW TTQDEGAAIGLAWIPYFGPAAEGIYIEGLMHNQDGLICGLRQLANETTQALQLFLRAT TELRTFSILNRKAIDFLLQRWGGTCHILGPDCCIEPHDWTKNITDKIDQIIHDFVDKTL PDQGDNDNWWTGWRQWIPAGIGVTGVIIAVIALFCICKFVF B. scytovirin GSGPTYCWNEANNPGGPNRCSNNKQCDGARTCSSSGFCQGTSRKPDPGPKGP TYCWDEAKNPGGPNRCSNSKQCDGARTCSSSGFCQGTAGHAAA Figure 2. Derived complex from interaction between scytovirin and Ebola virus glycoprotein.