Discovery of mechanics of drug targets for COVID-19
Scientist unravel inner workings of cell receptors involved in
inflammatory diseases

Date:
September 27, 2021
Source:
McGill University
Summary:
Researchers have discovered the working mechanism of potential drug
targets for various diseases such as cancer, rheumatoid arthritis,
and even COVID-19. The findings uncover the inner workings of cell
receptors that are involved in cancer progression and inflammatory
diseases.



FULL STORY ==========================================================================
A team of international researchers, including McGill Professor Ste'phane Laporte, have discovered the working mechanism of potential drug targets
for various diseases such as cancer, rheumatoid arthritis, and even
COVID-19. The findings published in Molecular Cell uncover the inner
workings of cell receptors that are involved in cancer progression 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 body, 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 spearheaded the study. "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." Using cutting-edge technologies such as
CRISPR and cryogenic electron microscopy, the researchers unraveled
the inner workings of C5aR2, providing an additional opportunity 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 sever 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,"
says Ste'phane Laporte, a Professor in the Faculty of Medicine and
Health Sciences.

Cells in the human body are surrounded by receptors that are important
drug targets where medicines produce their beneficial effects. These
receptors work as messengers because they receive and transmit signals
that allow the cells to trigger physiological processes in our body,
the researchers explain.

"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," concludes Arun Shukla.

About this study "Intrinsic bias at non-canonical, b-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, Ste'phane A. Laporte, Trent M. Woodruff, Asuka Inoue and Arun K. Shukla
was published in Molecular Cell.

This research was supported by the DBT Wellcome Trust India Alliance, Department of Science and Technology (DST), Science and Engineering
Research Board (SERB), Council of Scientific and Industrial Research
(CSIR), Lady Tata Memorial Trust, and the Canadian Institutes of Health Research.

========================================================================== Story Source: Materials provided by McGill_University. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. 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, Ste'phane A. Laporte,
Trent M. Woodruff, Asuka Inoue, Arun K. Shukla. Intrinsic bias
at non-canonical, b-arrestin- coupled seven transmembrane
receptors. Molecular Cell, Sept. 27, 2021; DOI:
10.1016/j.molcel.2021.09.007 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/09/210927121234.htm

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