New tool outsmarts COVID-19 virus to help vaccine development

September 09, 2020

Melbourne researchers have developed a tool to monitor mutations that make it difficult to develop coronavirus (COVID-19) vaccines and drugs.

Ensuring treatments remain effective as the virus mutates is a huge challenge for researchers. The powerful new tool harnesses genomic and protein information about the virus and its mutations to aid drug and vaccine development.

University of Melbourne Associate Professor David Ascher and his team at the Bio21 Molecular Science and Biotechnology Institute and the Baker Heart and Diabetes Institute developed the software tool and library, dubbed COVID-3D.

Published in Nature Genetics, COVID-3D contains information about all the protein structures that coincide with the SARS-CoV-2 (COVID-19) genome, including every known genetic mutation and its resultant mutant protein structure.

"Although the SARS-CoV-2 virus is a relatively new pathogen, its ability to readily accumulate mutations across its genes was evident from the start of this pandemic," Associate Professor Ascher said.

"In the context of therapeutic drug design and discovery, these mutations, and the patterns by which they accumulate within the virus' protein structures, can affect the ability of vaccines and drugs to bind the virus, or to create a specific immune response against it. Because of this, scientists must not only try to control the virus, but outsmart it by predicting how it will change over time."

Several international universities and research institutions already use COVID-3D in vaccine and treatment development.

"At Bio21 it is being used as part of ongoing efforts to understand and develop drugs to treat COVID-19," Associate Professor Ascher said.

To develop COVID-3D, Professor Ascher's team analysed the genome sequencing data of over 120,000 SARS-CoV-2 samples from infected people globally, including those that uniquely affect Australia, to identify mutations within each of the virus' proteins. They tested and analysed the mutations' effects on their protein structure using computer simulations.

This data was used to calculate all the biological effects of every possible mutation within the genome. To help researchers account for possible future mutations, the team analysed mutations in the related coronaviruses SARS-CoV and Bat RaTG13.

Mutations or changes in an organism's genetic material are natural 'errors' in the cell replication process. They can give the virus new 'powers' of survival, infectivity and virulence. Fortunately, the researchers found SARS-CoV-2 is mutating slower than other viruses such as influenza, with about two new changes in its genome every month.

COVID-3D can help researchers recognise how mutations operate and identify more effective vaccine and drug targets.

"It is only when you know how a mutation will affect the 3D shape of a protein, that you can predict if it will compromise your drug's ability to bind," Associate Professor Ascher said.

"As the global scientific and medical community gains better understanding of the biology behind the SARS-CoV2 infection and disease, this will be a powerful resource to predict problems with mutations and to guide the development of more effective therapies.

"COVID-3D continues to be updated with new protein structures, mutations and analyses to keep ahead of mutations that cause problems and increasing our understanding of the SARS-CoV-2 mechanisms of disease."
-end-
Study link: https://www.nature.com/articles/s41588-020-0693-3

University of Melbourne

Related Genome Articles from Brightsurf:

Genome evolution goes digital
Dr. Alan Herbert from InsideOutBio describes ground-breaking research in a paper published online by Royal Society Open Science.

Breakthrough in genome visualization
Kadir Dede and Dr. Enno Ohlebusch at Ulm University in Germany have devised a method for constructing pan-genome subgraphs at different granularities without having to wait hours and days on end for the software to process the entire genome.

Sturgeon genome sequenced
Sturgeons lived on earth already 300 million years ago and yet their external appearance seems to have undergone very little change.

A sea monster's genome
The giant squid is an elusive giant, but its secrets are about to be revealed.

Deciphering the walnut genome
New research could provide a major boost to the state's growing $1.6 billion walnut industry by making it easier to breed walnut trees better equipped to combat the soil-borne pathogens that now plague many of California's 4,800 growers.

Illuminating the genome
Development of a new molecular visualisation method, RNA-guided endonuclease -- in situ labelling (RGEN-ISL) for the CRISPR/Cas9-mediated labelling of genomic sequences in nuclei and chromosomes.

A genome under influence
References form the basis of our comprehension of the world: they enable us to measure the height of our children or the efficiency of a drug.

How a virus destabilizes the genome
New insights into how Kaposi's sarcoma-associated herpesvirus (KSHV) induces genome instability and promotes cell proliferation could lead to the development of novel antiviral therapies for KSHV-associated cancers, according to a study published Sept.

Better genome editing
Reich Group researchers develop a more efficient and precise method of in-cell genome editing.

Unlocking the genome
A team led by Prof. Stein Aerts (VIB-KU Leuven) uncovers how access to relevant DNA regions is orchestrated in epithelial cells.

Read More: Genome News and Genome Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.