null Using computer simulations in search of drugs against SARS-CoV-2

The structure and interactions of the coronavirus S-protein are studied using computer simulations. The goal is to find areas on the surface of the S-protein to which the drug could bind while preventing the virus from binding the ACE2 protein on the surface of human cells.

Using computer simulations in search of drugs against SARS-CoV-2

“Invade and hijack the cell”, a key and first step in the viral infection. The New SARS-Cov-2 uses its surface Spike glycoproteins (S-protein) to invade human cell through the ACE2 (Angiotensin-Converting Enzyme 2) receptor.

In a study conducted at the University of Turku, the structure of the coronavirus S-protein is studied using computer simulations, in which the structure of the protein and its interactions with, for example, solvents and other small molecules can be examined at the atomic level.

Our goal is to find areas on the surface of the S-protein to which the drug could bind while preventing the virus from binding the ACE2 protein on the surface of human cells. In this way, the spread of the virus in our body would be prevented, and the viral infection could be significantly slowed down if not stopped, says Olli Pentikäinen, Professor of Medicinal Chemistry.

Similarly, we are investigating whether, for example, a drug or a substance in food can accelerate the entry of the virus into the cell, in which case it could be recommended to avoid such products, Pentikäinen continues.

In drug discovery, the research group utilizes advanced technology. For example, doctoral student Elmeri Jokinen recently visited University of Michigan, USA, to gain insight into computer simulations where the protein surface is probed with various organic solvents to reveal advantageous binding sites for small molecules.

The shape and electrostatic properties of binding sites are used to create models to search for suitable small molecules in the screening of virtual molecular databases, says Pentikäinen.

The foremost interest of the study is to search for molecules with already known pharmacological properties, such as approved or emerging drugs, as well as various chemicals and natural compounds present in our environment. To date, several potential molecules that could impair the interaction between the S-protein and the ACE2 receptor have been identified in the study. Next, the identified molecules will be experimentally tested in collaboration with researchers from Shanghai Jiaotong University (China) and the University of Turku.

The computer simulations performed in the study and the screening of molecular databases have been performed with the supercomputer of CSC - Center for Science Information Technology Ltd. The computing capacity reserved by CSC for research against the COVID-19 pandemic has significantly accelerated the progress of the research.

At best, screening of virtual databases has been able to process up to millions of compounds per day. Another aim of the project has been to develop a platform to search drug molecules for rapidly spreading disease, such as the current coronavirus disease, in the future.

 – Visiting senior scientist Gopinath Krishnasamy and doctoral student Sami Kurkinen have created a molecular database that can be used in drug screening in the future, says Pentikäinen.

This will allow us to react quickly and, at best, identify some known, safe drug to control the spread of the disease.

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Elmeri Jokinen, University of Turku