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Accelerated Drug Discovery with Oracle Cloud Infrastructure High Performance Computing

Yogi Pandey, Leandro Oliveira Bortot, and Paulo S. L. de Oliveira (Brazilian Biosciences National Laboratory, and Brazilian Center for Research in Energy and Materials (LNBio/CNPEM))

Humanity has witnessed an unprecedented crisis over the past months. With the emergence of the COVID-19 pandemic, Life Sciences researchers across the globe have been working tirelessly to find a treatment for the disease. Oracle Cloud Infrastructure high-performance computing (HPC) is playing its part by enabling researchers with access to cutting-edge hardware.

Scalable HPC infrastructure on Oracle Cloud Infrastructure (OCI) significantly speeds up the drug discovery process. OCI has supported researchers across the globe in their efforts to find a treatment for COVID-19, including the Brazilian Biosciences National Laboratory (LNBio). Researchers at LNBio have made advancements in the fight against COVID-19 through Oracle for Research, a new program that provides Oracle Cloud credits and related resources to projects that drive meaningful change in the world.

A Race for a Cure

Given the prevailing situations, researchers are in a race to find a COVID-19 vaccine and treatment. The drug discovery life cycle from the beginning of the project to regulatory approvals takes over 12 years. Also, only one out of 5,000 experimental drug molecules are approved for safe human usage. With COVID-19, time is a luxury that the researchers don’t have.

Keeping this fact in mind, the researchers at LNBio are attempting to follow a drug-repurposing approach. In this approach, a medicine pre-approved by the regulatory agencies for treatment of another disease is tested for treatment of a newly emerging disease. This approach may significantly cut down the time it takes to make a treatment available to the larger population.

The team of researchers at LNBio and the Brazilian Center for Research in Energy and Materials (CNPEM), part of the Brazilian Ministry of Science, Technology and Innovation, are working on identifying drug molecules, which attach to viral proteins and stop the virus from causing infection or multiplying inside the human body (Figure 1). This process can help patients to recover from COVID-19, because it helps the immune system to fight the infection by decreasing the number of viral particles inside the patient’s body.

Figure 1. Researchers at the Brazilian Biosciences National Laboratory (LNBio) and the Brazilian Center for Research in Energy and Materials (CNPEM) are targeting active sites (from left to right) nucleocapsid, 3CL-protease, and PL-protease. Drug molecules blocking these active sites stop the virus from causing infection or multiplying inside our body. (Courtesy: LNBio)

Process of Drug Repurposing

Researchers of LNBio started with 2,097 pre-approved drug molecules available in the DrugBank database. They performed the process of virtual screening, where 419,400 conformations of these 2,097 molecules attached to the target locations on virus were generated through molecular docking algorithm. Briefly, this algorithm takes the atom Cartesian coordinates of molecules and applies random rotation in all vectors formed by rotatable bonds, generating thousands of possible conformations for the original molecule. Each conformation is rotated and translated to generate a “molecular pose” in the active site of viral protein. An empirical score function is calculated for each pose.

This process is repeated millions of times for each target. A customized ranking algorithm narrows down the prospects to 200 best poses. Finally, using these 200 poses generated through virtual screening, molecular simulations help identify three drug molecules, which have a potential of stopping multiplication of the virus (Figure 2). Solving this problem is computationally intensive and requires scalable robust infrastructure, which is often difficult for research organizations to access quickly and cost effectively.