Artificial Proteins as COVID-19 Drug Candidates Precisely Designed and Produced by DGIST

The Daegu Gyeongbuk Institute of Science and Technology (DGIST) announced on July 29 that it has succeeded in precisely designing and producing COVID-19 drug candidates by supercomputer-based simulation.

“We designed 11 types of artificial proteins as the candidates, established production processes regarding the proteins, analyzed the neutralization functions and the human cell toxicity, and completed patent application,” it explained.

The institute designed the artificial proteins to an atomic level by supercomputing simulation. As a result, it could design amino acid sequences and three-dimensional structures with regard to the 11 candidate substances that prevent contact between the COVID-19 virus and human cells.

At present, worldwide COVID-19 drug development is in progress in four different ways, that is, drug repositioning, convalescent plasma therapy, antibody therapy and new drug development based on synthetic chemical substances.

The DGIST’s approach, which is completely different from the four methods, is based on statistical thermodynamics and biophysics as well as the atomic-level supercomputing simulation. The artificial proteins are characterized by preventing binding between the ACE2 receptor protein in a human cell and the spike RBD protein on the surface of the virus for attachment to a host cell.

The institute already confirmed the structural, thermodynamic and immunogenic stability of the 11 candidate substances computationally and scientifically. Also, it developed cloning, expression, purification and production processes for the proteins and produced them on its own. High-purification production has been completed for seven out of the 11 and the same process is about to be completed for the rest. The institute carried out advanced mass spectrometry (MALDI-TOF, Q-Exactive and Q-TRAP) and circular dichroism analysis to confirm the stability of the secondary protein structures, the normality of the amino acid sequences, etc.

The constants of binding between the produced artificial proteins and the spike RBD protein were measured in microscale thermophoresis experiments. It was confirmed as a result that the spike RBD protein can be neutralized, that is, the artificial proteins’ binding to the spike RBD protein is stronger. The 11 proteins include PEP9. It was injected into six human cell lines (human embryonic kidney, hepatic, cerebral immune, lung, kidney and lung cancer) and resulted in no toxicity.