COVID-19 has taken the globe by storm and completely disrupted the world’s norm. As a disease with such a huge effect on people’s quality of life, researchers across the world have been racing against time to understand the infectious mechanisms of SARS-CoV-2, the virus that causes COVID-19.
So far, a lot of research has gone into how antibodies interact with SARS-CoV-2 proteins and the genome, with little known about how the virus interacts with human RNA once it infects a cell. This knowledge gap sets the aim for Yue Wan, Associate Director of Epigenetic and Epitranscriptomic Systems at A*STAR’s Genome Institute of Science (GIS) and A*STAR Scholarship recipient.
“SARS-CoV-2 is known to degrade many host proteins to facilitate its replication and translation,” explained Wan. “Emulating our previous work on the dengue virus and the Zika virus, we mapped the SARS-CoV-2 genome to identify structural elements important for its growth and survival.”
Wan and her collaborators, Roland Huber from Bioinformatics Institute (BII) and Lin-Fa Wang from Duke-NUS Medical School, led their team in using different high throughput RNA and interactome techniques and observed how the virus genome interacted with itself and host RNA. Viral RNA plays a key role in helping the virus produce its proteins. As the virus' genetic material closely resembles that of human cellular RNA, the human cell is, therefore, ‘hijacked’ to help the virus to produce its proteins.
They found that the SARS-CoV-2 genome binds to SNORD27, a small nucleolar RNA that can both stabilize the virus and destabilize host RNAs by sequestering important cellular machinery to the viral genome and away from the host. This, along with the production of Nsp1 protein that degrades cellular RNAs, ensures a multi-pronged approach for the virus’ survival.
The researchers also successfully mapped a Singapore-variant of the virus to determine its difference from the wildtype SARS-CoV-2 genome.
“These genomic maps will eventually have a therapeutic consequence as they can serve as a useful resource for understanding how the virus genome folds and how we can target it using small molecules,” said Wan.
Looking ahead, Wan believes that more studies on the different SARS-CoV-2 variants should be done to understand which structural elements are functionally important and common to all variants. This knowledge is key to understanding the features that enable SARS-CoV-2 survival, such as replication, infectivity and the ability to evade host immune surveillance.
The A*STAR-affiliated researchers contributing to this research are from Genome Institute of Science (GIS) and Bioinformatics Institute (BII).
