Zika problem introduction

In 2016 the Zika virus spread rapidly from south America to north America affecting also some island in the Pacific and the southeast Asia, so WHO declared Zika a pandemic issue. Zika virus is a flavivirus transmitted by mosquitoes, mainly Aedes aegypti and also albopictus. The virus determines mild symptoms as fever, rash, conjunctivitis, muscle and joint pain, malaise or headache, but Zika virus infection during pregnancy can spread from the mother to the baby and can cause severe defects to the fetuses, infact, infants often born with microcephaly and other congenital malformations and developmental problems. Additionally, an increased risk of neurologic complications is associated with Zika virus infection in adults and children, including Guillain-Barré syndrome, neuropathy and myelitis.


CADD introduction

Computer-aided drug design (CADD) techniques are used to speed-up the early-stage drug development allowing the selection of new active compounds. Through virtual screening large virtual chemical libraries can be screened to find active molecules for query targets. Virtual screening techniques can be divided in ligand-based and structure-based if they use the structure of an active molecule to find similar compounds or they use the structure of the target to identify putative ligands, respectively. In the last years, the growing availability of protein structures, resolved by structural biologists, progressively raised the possibility to deploy structure-based drug design. Key for the success of the structure-based drug design is the evaluation of a chemical space big enough to allow the identification of chemical structures having the best complementary pattern of interactions with the biological target under investigation along with other phys-chem characteristics as well as novelty and synthesis feasibility.


The Antarex project

The ANTAREX research project has been granted in the H2020 Future and Emerging Technologies program on High Performance Computing. The project involves CINECA, the Italian Tier-0 Supercomputing Centre and IT4Innovations, the Czech Tier-1 Supercomputing Center. Being one of the nineteen research projects in FET-HPC-2014, ANTAREX brings its partners on the forefront of the European research in HPC. The project just started on September the 1st, 2015. The main goal of the ANTAREX project is to provide a breakthrough approach to map, runtime manage and autotune applications for green and heterogeneous HPC (High Performance Computing) systems up to the exascale level. The ANTAREX project is driven by two use cases chosen to address the self-adaptivity and scalability characteristics. Here we present an application scenario linked to a biopharmaceutical HPC application for accelerating drug discovery deployed on the 1.2 PetaFlops heterogeneous NeXtScale Intel-based IBM system at CINECA.


The simulation

To demonstrate the obtained results in terms of code optimization and scalability we have selected the Zika pandemic crisis to support and promote the identification of novel drugs able to address the unmet medical need in terms of effective therapies. We select 26 binding sites identified from the already resolved crystal structures of 5 zika proteins: NS5, NS1, NS2B/NS3, NS3 and the envelope protein. For this experiment, we have created a virtual chemical space of 1.2 Billion small molecular weight molecules. The evaluation of such a huge chemical space is possible thanks to the outcome of the ANTAREX project and the almost 1million core available at CINECA.


Outcome

Intention of the ANTAREX partners is to make available to the research community the outcome of the simulation to support and speed up the discovery of novel treatment to fight the zika pandemic.