Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.
melinamottin@gmail.com
Dr. Melina Mottin
Carolina Horta Andrade Alexander L. Perryman Sean Ekins
13th Jul 2017
http://open...
Transmission:
• mosquito
• sperm
• blood
• breast milk
OpenZika Project: Antivirals
• IBM philanthropic initiative
• idle ...
Transmission:
• mosquito
• sperm
• blood
• breast milk
OpenZika Project: Antivirals
• IBM philanthropic initiative
• idle ...
OpenZika = # crunching for a cure
Ekins, S.; Perryman, A. L.; Horta Andrade, C. PLoS Negl. Trop. Dis. 2016, 10, e0005023.
...
NS3 helicase structure
and binding sites
• unwinds viral RNA strand
• facilitates replication of the viral genome
-> attra...
Dynamic behavior of
ZIKV NS3 helicase
Mottin, M, Braga, R C, da Silva R A, da Silva J H M, Perryman, A L, Ekins, S, Andrad...
NS3 helicase selected candidates
Target specific
ZIKV NS3
Helicase (5JMT)
ZIKV NS3 Helicase
with RNA (5GJB)
150 cpds
22 cp...
ZIKV Selected candidates
Full data sets
ZINC subsets: FDA approved + NIH
clinical collection+ Prestwick
Chemicals
3600 cpd...
NS1
NS2B-NS3 protease
NS3 helicase
NS5 RNA polymerase
20.000 volunteers donating CPU time
Approximate total # of results n...
Future Steps
Protein - hit
MD simulations
NS3
Helicase
NS5
Methiltransferase
other Zika proteins
Virtual Screening
Enzymat...
OpenZika Team
Alexander Perryman
Wim Degrave
Ana Carolina Ramos
João H. Martins
Joel Freundlich
Pedro Torres
Carolina Andr...
Acknowledgments
melinamottin@gmail.com
Upcoming SlideShare
Loading in …5
×

Opening the Discovery of New Antiviral Candidates Against Zika Virus and Insights into Dynamic Behavior of NS3 Helicase

241 views

Published on

The main goal of this project is to accelerate the discovery of drug candidates against the zika virus, through the World Community Grid.

  • Be the first to comment

  • Be the first to like this

Opening the Discovery of New Antiviral Candidates Against Zika Virus and Insights into Dynamic Behavior of NS3 Helicase

  1. 1. melinamottin@gmail.com Dr. Melina Mottin Carolina Horta Andrade Alexander L. Perryman Sean Ekins 13th Jul 2017 http://openzika.ufg.br Opening the Discovery of New Antiviral Candidates Against Zika Virus and Insights into Dynamic Behavior of NS3 Helicase Rodolpho Braga Roosevelt A. da Silva João H. Martins
  2. 2. Transmission: • mosquito • sperm • blood • breast milk OpenZika Project: Antivirals • IBM philanthropic initiative • idle processing power of computer/mobile phone • massive supercomputing data • Free of charge!
  3. 3. Transmission: • mosquito • sperm • blood • breast milk OpenZika Project: Antivirals • IBM philanthropic initiative • idle processing power of computer/mobile phone • massive supercomputing data • Free of charge!
  4. 4. OpenZika = # crunching for a cure Ekins, S.; Perryman, A. L.; Horta Andrade, C. PLoS Negl. Trop. Dis. 2016, 10, e0005023. Zika proteins Virtual screening Molecular docking > 30 millions of compounds Zika virus proteins
  5. 5. NS3 helicase structure and binding sites • unwinds viral RNA strand • facilitates replication of the viral genome -> attractive target for antivirals www.ftmap.bu.edu Mottin, M, Braga, R C, da Silva R A, da Silva J H M, Perryman, A L, Ekins, S, Andrade C H; Biochem Biophysical Res Comm; 2017, in press.
  6. 6. Dynamic behavior of ZIKV NS3 helicase Mottin, M, Braga, R C, da Silva R A, da Silva J H M, Perryman, A L, Ekins, S, Andrade C H; Biochem Biophysical Res Comm; 2017, in press. MD Program: Gromacs 5.1.2 Amber Force Field99SB-ILDN MD trajectories: 100 ns
  7. 7. NS3 helicase selected candidates Target specific ZIKV NS3 Helicase (5JMT) ZIKV NS3 Helicase with RNA (5GJB) 150 cpds 22 cpds 2 cpds 232 cpds 74 cpds 4 cpds free energy filter Molecular Docking (AutoDock Vina) Selected hits QSAR phenotypic model MedChem based inspection ZINC subsets: FDA approved + NIH clinical collection+ Prestwick Chemicals 7600 compounds Dr. Jair Siqueira-Neto
  8. 8. ZIKV Selected candidates Full data sets ZINC subsets: FDA approved + NIH clinical collection+ Prestwick Chemicals 3600 cpds QSAR phenotypic model 51 cpds consensus model prediction, visual inspection, $$$ 9 virtual hits Zika proteins Dataset for modeling Zika bioassay (AID1224857) ~ 5,700 compounds Balanced dataset: 90 compounds Active<10µM
  9. 9. NS1 NS2B-NS3 protease NS3 helicase NS5 RNA polymerase 20.000 volunteers donating CPU time Approximate total # of results now ~ 3,5 billion docking jobs submitted* ~ 1,9 billion results received* Updated Outcomes OpenZika Project *84 target sites: ZIKV, Dengue Virus, Hepatitis C Virus, Yellow Fever Virus, Japanese Encephalitis Virus Compounds database
  10. 10. Future Steps Protein - hit MD simulations NS3 Helicase NS5 Methiltransferase other Zika proteins Virtual Screening Enzymatic assays
  11. 11. OpenZika Team Alexander Perryman Wim Degrave Ana Carolina Ramos João H. Martins Joel Freundlich Pedro Torres Carolina Andrade Sean Ekins Rodolpho Braga Melina Mottin Roosevelt Silva Jair Siqueira-Neto Bruno Neves Joyce Borba Cleber Melo-Filho Be a WCG volunteer and help us! http://openzika.ufg.br
  12. 12. Acknowledgments melinamottin@gmail.com

×