The Big Question: NTU’s Richard Sugrue on SARS-CoV-2 Challenges

by | Mar 2, 2020 | Biology, School of Biological Sciences

Richard Sugrue is an Associate Professor at the School of Biological Sciences, Nanyang Technological University, Singapore. His research focuses on the biology of RNA viruses. In particular, his lab is trying to understand, at the molecular level, the role that host-cell factors play during specific stages of the virus replication cycle, such as virus replication and assembly.

His current focus is on the role that specialized lipid membrane structures, called lipid-rafts, play during Paramyxovirus-infection. This research will be extended to examine influenza and dengue viruses, two infectious agents that are of global and regional medical importance. It is hoped that a detailed understanding of the intimate relationship between these individual viruses and the host-cell during infection will lead to the development of novel antiviral strategies.

What is the biggest question regarding SARS-CoV-2?

In my opinion the big question is actually two closely related questions. How did SARS-CoV-2 enter the human population, and how will SARS-CoV-2 evolve as it circulates in the human population? Currently, the virus appears to cause severe disease outcome mainly in the elderly and in individuals with underlying health issues, but it is not clear if this will change in the future.

Understanding how the biological properties of the virus change as it circulates in the human population will have important consequences for understanding its future impact on human health. In addition, understanding of the underlying factors that led to SARS-CoV-2 appearing in the human population may also tell us how similar events could occur in the future.

Why is it significant?

Many viruses that we think of as causing human disease actually have an animal origin. Virus transmission from an animal to human population (zoonosis) is an important factor in human virus disease outbreaks. The SARS-CoV-2 appears to have originated in bats, and either directly, or indirectly via another animal species, it has made the species jump into the human population.

Although the virus has found the key with which to enter the human door, additional adaptations may be required for its maintenance and efficient transmission within the human population. These adaptations are mediated by the selection of sequence changes in the SARS-CoV-2 genome as the virus evolves.

However, it is not clear if these genetic changes will also be associated with increased disease severity in a wider spectrum of individuals in future. If SARS-CoV-2 infection becomes associated with increased disease severity in healthy young adults, this will become a ‘game changer’ in the SARS-CoV-2-human interaction.

Where is the answer likely to come from?

This zoonotic event is now being examined in real-time, and the information obtained should shed light on how SARS-CoV-2 is transmitted in humans. It should also provide a better understanding of the future consequences of SARS-CoV-2 in relation to human health. In this context, virus surveillance and virus genome sequence analysis provide vital information about the evolution of SARS-CoV-2.

However, this information alone is not sufficient to either understand the basis for its human adaptation, or to develop efficient control measures. Therefore, research on the biological properties of the virus should provide important insights into the interaction of the virus and its human host. This will provide an understanding for the basis for the zoonotic transmission and maintenance of SARS-CoV-2 in the human population, and it will also facilitate the development of future antiviral control measures.

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