IIT Kanpur Unveils Insights Into Drugs Working Mechanism Via Advanced Molecular Visualization

The IIT Kanpur research team led by Prof. Arun K. Shukla, Department of Biological Sciences and Bioengineering, provided new insights into the understanding of the molecular mechanism of  Cholesterol-lowering drugs like Niacin and others.

The researchers used cryogenic-electron microscope (cryo-EM) technology, to visualize the receptor molecules activated by Niacin. The research was published in Nature Communications.

Prof. Shukla said that Niacin is commonly prescribed to patients with high cholesterol levels. The drugs stimulate good cholesterol and remove bad cholesterol from the blood. However, it can cause side effects such as skin redness and itching which causes patients to stop treatment. The Niacin when binds with the Hydroxycarboxylic acid receptor 2 (HCA2) (GPR109A) helps in the widening of blood vessels which leads to the experience of red, flushing skin reaction.

He added that the molecular-level visualization of Niacin and receptor molecules will help in designing drugs with better efficacy and fewer side effects. The research will also help in developing related drugs for Cholesterol and other conditions such as multiple sclerosis.

Prof. S. Ganesh, Director, of IIT Kanpur also said the research will unveil new avenues to design better therapeutic agents for other medical issues. “This achievement exemplifies our dedication to addressing real-world health challenges through innovation and excellence in research. The acceptance of the research for publication is a testament to the quality and high standards of R&D at IIT Kanpur”, said he.

The study was supported by the Science and Engineering Research Board (SERB) and spearheaded by Prof. Arun K Shukla at IIT Kanpur. The other members of the team involved Dr. Manish Yadav, Ms. Parishmita Sarma, Mr. Jagannath Maharana, Mr. Manisankar Ganguly, Ms. Sudha Mishra, Ms. Annu Dalal, Mr. Nashrah Zaidi, Mr. Sayantan Saha, Ms. Gargi Mahajan, Mr. Vinay Singh, Ms. Saloni Sharma, and Dr. Ramanuj Banerjee.

Notably, with near-atomic resolution, the three-dimensional (3D) structure of biological molecules and complexes can be clarified using cryo-electron microscopy (Cryo EM). This method traps the material in vitreous ice by quickly freezing it to temperatures below -150 °C. After that, the sample is seen from various perspectives using an electron microscope. This produces a series of two-dimensional (2D) projections on the specimen as an electron beam passes through it. From these projections, a 3D model of the material is subsequently reconstructed using sophisticated computational processes.