Experts unravel inner workings of cell receptors involved in various diseases

A group of international scientists along with Stéphane Laporte, a McGill Professor, revealed the operational mechanism of possible drug targets for numerous diseases like rheumatoid arthritis, cancer, and even COVID-19.

Experts unravel inner workings of cell receptors involved in various diseases
Image Credit: McGill University.

Their findings reveal the inner mechanisms of cell receptors engaged in inflammatory diseases and cancer progression. The observations were published in the Molecular Cell journal.

The complement system is an integral part of our body’s defense mechanism against pathogenic attacks including viruses. When bacteria or viruses enter our body, the complement system is activated, including two different membrane receptors called C5aR1 and C5aR2.”

Arun Shukla, Joy Gill Chair Professor, Indian Institute of Technology Kanpur

Professor Arun Shukla who led the research stated, “While activation of the complement system is essential to combat harmful pathogens, excessive and sustained activation leads to inflammation, even life-threatening conditions like the ones responsible for severe complications in COVID-19.”

The scientists employed state-of-the-art technologies like cryogenic electron microscopy and CRISPR to reveal the mechanism of C5aR2, offering further opportunities for therapeutic targeting for COVID-19.

To treat COVID-19, some scientists are already trying to block the activation of the C5aR1 receptor and clinical trials are already underway for Avdoralimab in patients with COVID-19 induced severe pneumonia. Our study opens up the possibility of targeting C5aR2 by designing new drug molecules that can bind to this receptor and block its activation and inflammation response.”

Stéphane Laporte, Professor, Faculty of Medicine and Health Sciences, McGill University

Cells present in the human body are enclosed by receptors that are vital drug targets where medicines generate their useful effects. These receptors act as messengers as they receive and transmit signals that enable the cells to induce physiological processes in the body, the experts elaborated.

We are very excited to decipher the finer details of these receptors using cutting-edge technologies. Such information should enhance our fundamental knowledge about cellular signaling and allow us to translate our findings into novel drug discovery.”

Arun Shukla, Joy Gill Chair Professor, Indian Institute of Technology Kanpur

Source:
Journal reference:

Pandey, S., et al. (2021) Intrinsic bias at non-canonical, β-arrestin-coupled seven transmembrane receptors. Molecular Cell. doi.org/10.1016/j.molcel.2021.09.007.

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