Soumya Shraddhya Paul, Amity University, Noida
COVID-19 pandemic has caused a lot of turmoil all around the world. According to WHO nearly 164 million people were infected worldwide out of which 3.4 million people lost their lives worldwide. Now, as we know COVID 19 is a respiratory disease caused by SARS-C0V-2 which belongs to the family of Coronaviridae. It is an enveloped, single-stranded RNA, positive sense betacoronavirus which exclusively only affects the mammalians.
To generate SARS-CoV-2 RNA, cells need to assemble their RTCs correctly and efficiently as a result of a coordinated transcription and replication cascade.
The study
The SARS-CoV-2 has a relatively large RNA genome and utilizes sophisticated replication/transcription complexes (RTCs) to establish efficient infection. RTCs are mainly composed of proteins such as nonstructural proteins and nucleocapsid proteins. In a recent study by Weifan Xu and colleagues, the researchers tried to show how phase separation in cellulo can lead to a novel interaction screening strategy called compartmentalization of protein-protein interactions in cells (CoPIC). With the help of CoPIC screening, we can map the interaction network among the RTC-related viral proteins.
The analysis identifies a total of 47 binary interactions between 14 proteins governing replication, translation, and discontinuous transcription of Coronaviruses. Further study using CoPIC reveals the existence of extensive ternary complexes based on these components this gives rise to potential higher-order complexes.
All in all, the results of this study were able to demonstrate an efficient and robust interaction screening approach that identifies a complex network of interactions between factors related to RTC. Which should provide the basis for an increased understanding of SARS-CoV-2 biology and the development of therapeutic solutions for COVID-19.
The outcome
As we learn more about SARS-CoV-2 molecular architectures, we must dissect the nonstructural protein interaction network and thus gain a better understanding of RTC assembly. Based on phase separation in cells in order to screen interactions, we have developed a new interaction screening strategy called CoPIC (compartmentalization of protein-protein interactions in cells).
The current study established a sensitive method for identifying PPIs in living cells and thereby constructed a network of interactions between the factors associated with SARS-CoV-2 RTC. As a result of obtaining data from other methods as well as identifying interactions, the most interesting and striking are those that occur between core viral enzymes and the corresponding higher-order complexes.
Despite the limited understanding of the function of the majority of intraviral PPIs, the understanding of networks is a powerful resource for figuring out how they modulate the replication/transcription of the SARS-CoV-2 genome. The extensive interaction landscape among intraviral proteomes seems to be the norm, underscoring the crucial roles of PPIs in the life cycle. Hence the disruption of these intraviral PPIs would likely provide therapeutic opportunities against SARS-CoV-2. Notably, we have been already actively engaging in high-throughput screening for drugs disrupting essential PPIs within SARS552 CoV-2 using CoPIC.
Also read: A special protein in rice to protect it against viral infection
Reference:
- Xu, W., Pei, G., Liu, H., Ju, X., Wang, J., Ding, Q., & Li, P. (2021). Compartmentalization-aided interaction screening reveals extensive high-order complexes within the sars-cov-2 proteome. Cell Reports, 109482. https://doi.org/10.1016/j.celrep.2021.109482
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Author info:
Soumya Shraddhya Paul is an undergrad biotechnology student who worked in building 3D prosthetics in Base Hospital Delhi Cantt, and holds a key interest in nutraceuticals and enzymology.
Publications:
- https://bioxone.in/news/worldnews/understanding-b-cell-genomics-to-fight-against-covid-19/
- https://bioxone.in/news/worldnews/the-current-ebola-epidemic-comes-to-an-end/
- https://bioxone.in/news/worldnews/epigenetic-changes-can-cause-permanent-changes-to-offsprings/
- https://bioxone.in/news/worldnews/crispr-act-3-0-a-revolution-in-plant-gene-technology/
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