Sars-CoV-2 virus can change its shape to improve survival: Singapore study

Scientists found that the virus' ribonucleic acid can fold into complex and dynamic shapes for its growth and survival when inside infected cells.
Scientists found that the virus' ribonucleic acid can fold into complex and dynamic shapes for its growth and survival when inside infected cells.PHOTO: AFP
Dr Wan said the findings can help to inform other researchers on the regions in the virus RNA that can be targeted for drug development.
Dr Wan said the findings can help to inform other researchers on the regions in the virus RNA that can be targeted for drug development.PHOTO: ST FILE

SINGAPORE - Scientists here have made an important discovery about the shape and structure of the Sars-CoV-2 virus' genetic material that can help in producing more effective drugs to treat Covid-19.

They found that the virus' ribonucleic acid (RNA) can fold into complex and dynamic shapes for its growth and survival when inside infected cells.

The team which comprised researchers from Duke-NUS Medical School, as well as the Genome Institute of Singapore (GIS) and Bioinformatics Institute (BII) - units under the Agency for Science, Technology and Research (A*Star) - also discovered that the virus RNA can interact with a lot of the human cell's RNA to make use of it for its own survival.

"Aside from understanding the shape that the virus takes when inside human cells, recent work has also shown that its shapes are also very important for drugs targeting the RNA, which was what prompted us to start this project," said Dr Wan Yue, group leader of the Laboratory of RNA Genomics and Structure.

Dr Wan, who is also associate director of Epigenetic and Epitranscriptomic Systems at GIS, led the study, which was published in the scientific journal Nature Communications on Wednesday (Aug 25).

The Sars-CoV-2 virus, which causes Covid-19, has a single-strand genome that is made up of RNA as its genetic material.

The RNA plays a key role in helping the virus produce its proteins. When the virus infects and enters the human cell, the spike protein on the surface of its cell binds with the human or host cell receptor.

It then releases its genome into the host cell, where the RNA is translated to make viral proteins.

As the virus' genetic material closely resembles that of human cellular RNA, the human cell is therefore "tricked" into helping the virus to create its proteins.

These viral proteins are essential in helping the viral RNA replicate and infect more human cells.

While a lot of research has gone into how antibodies interact with the virus proteins and its genome, little is known about how the virus interacts with human RNA once it infects a cell.

The Singapore study tackles this gap.

Aside from the discovering the shape and structure of the Sars-CoV-2 virus' genetic material, the team also learnt that the virus binds with a small nucleolar RNA, or snoRNA, to steal its modification abilities.

The snoRNA modifies the body's translation machinery to enable the body to produce protein properly.

In stealing the modification abilities, this helps to stabilise the virus, making it more successful in infecting the host cells.

Dr Wan said the findings can help to inform other researchers on the regions in the virus RNA that can be targeted for drug development.

The study was carried out together with Dr Roland Huber, assistant principal investigator at the BII, and Prof Wang Linfa of the Emerging Infectious Diseases Programme at Duke-NUS Medical School.

The team had also compared the structures of the original, or wild-type Sars-CoV-2 virus, with a variant, and found that the latter has a region of its RNA deleted.

They also found shape differences between the wild type and the variant.

Studies are under way to determine how the different circulating variants can use its different shapes to replicate itself, said Dr Wan.