A team of international researchers, including McGill professor Stéphane Laporte, has discovered the mechanism of action of potential drug targets for various diseases such as cancer, rheumatoid arthritis and even COVID-19. The results published in Molecular cell Discover the inner workings of cell receptors that are involved in the progression of cancer and inflammatory diseases.
“The complement system is an integral part of our body’s defense mechanism against pathogenic attacks, including viruses. When bacteria or viruses enter our bodies, the complement system is activated, including two different membrane receptors called C5aR1 and C5aR2, ”says Arun Shukla, the Joy Gill Chair Professor at IIT Kanpur who led the study. “While activation of the complement system is essential to fighting harmful pathogens, excessive and prolonged activation leads to inflammation, even the life-threatening conditions that are responsible for the serious complications of COVID-19.”
Using state-of-the-art technologies such as CRISPR and cryogenic electron microscopy, the researchers deciphered the inner workings of C5aR2 and thus offered an additional option for the therapeutic focus on COVID-19. “To treat COVID-19, some scientists are already trying to block activation of the C5aR1 receptor, and clinical studies are ongoing for avdoralimab in patients with COVID-19-induced severe pneumonia. Our study opens up the possibility of C5aR2 by developing new drug molecules that can bind to this receptor and block its activation and inflammatory response, “says Stéphane Laporte, professor at the Faculty of Medicine and Health Sciences.
Cells in the human body are surrounded by receptors that are important targets for drugs on which drugs develop their positive effects. These receptors work as messenger substances because they receive and transmit signals that enable cells to trigger physiological processes in our body, the researchers explain.
“We are delighted to be able to decipher the finer details of these receptors using state-of-the-art technology. Such information should expand our basic knowledge of cellular signaling and enable us to translate our findings into the discovery of new drugs, ”concludes Arun Shukla.
About this study
“Intrinsic bias at non-canonical, β-arrestin-coupled seven transmembrane receptors” by Shubhi Pandey, Punita Kumari, Mithu Baidya, Ryoji Kise, Yubo Cao, Hemlata Dwivedi-Agnihotri, Ramanuj Banerjee, Xaria X. Li, Cedric S. Cui , John D. Lee, Kouki Kawakami, Jagannath Maharana, Ashutosh Ranjan, Madhu Chaturvedi, Gagan Deep Jhingan, Stéphane A. Laporte, Trent M. Woodruff, Asuka Inoue, and Arun K. Shukla was published in Molecular cell.
This research was funded by the DBT Wellcome Trust India Alliance, the Department of Science and Technology (DST), the Science and Engineering Research Board (SERB), the Council of Scientific and Industrial Research (CSIR), the Lady Tata Memorial Trust, and the Canadian Institutes of. supports health research.
Materials provided by McGill University. Note: The content can be edited in terms of style and length.