Flies to help with COVID-19 research
At the time of writing, COVID-19 has infected almost 150 million people, killing more than 3 million. COVID-19 has put the world on hold, including research. Now a new study just published in March 2021 (Zhu et al., 2021) by the Han laboratory from the University of Maryland School of Medicine, in Baltimore, is helping us understand this disease with the help of fruit flies.
Zhu and colleagues found that 90% of the proteins that interacts with COVID-19 in humans are conserved (i.e. similar) in flies. They then created transgenic flies able to express single COVID-19 proteins in flies, to study their impact on flies. They found that flies expressing the COVID-19 genes Orf6, Nsp6 and Orf7 had reduced viability and various tissue defects, including reduced trachea (the fly lungs) branching and muscle deficits.
Previous studies showed that Orf6 interacts with the nuclear export complex, which is a cellular machine deputed to move proteins outside of the cell nucleus. Zhu and colleagues identified that, in human cells, Orf6 is interacting with XPO1, a key component of the nuclear export complex. XPO1 is known to be bound by Selinexor, and FDA-approved inhibitor of nuclear transport. Zhu and colleagues testes tested Selinexor back in the flies overexpressing the COVID-19 protein Orf6, and found that 0.2 μM Selinexor was able to attenuate the impact of Orf6.
Overall, this study shows the feasibility of using flies as a model organism to perform research on COVID-19, and as a possible host for pharmacological screen to identify putative drugs to combat COVID-19.
Citation: Zhu, J. yi, Lee, J. G., van de Leemput, J., Lee, H., & Han, Z. (2021). Functional analysis of SARS-CoV-2 proteins in Drosophila identifies Orf6-induced pathogenic effects with Selinexor as an effective treatment. Cell and Bioscience, 11(1). https://doi.org/10.1186/s13578-021-00567-8
Zhu and colleagues found that 90% of the proteins that interacts with COVID-19 in humans are conserved (i.e. similar) in flies. They then created transgenic flies able to express single COVID-19 proteins in flies, to study their impact on flies. They found that flies expressing the COVID-19 genes Orf6, Nsp6 and Orf7 had reduced viability and various tissue defects, including reduced trachea (the fly lungs) branching and muscle deficits.
Previous studies showed that Orf6 interacts with the nuclear export complex, which is a cellular machine deputed to move proteins outside of the cell nucleus. Zhu and colleagues identified that, in human cells, Orf6 is interacting with XPO1, a key component of the nuclear export complex. XPO1 is known to be bound by Selinexor, and FDA-approved inhibitor of nuclear transport. Zhu and colleagues testes tested Selinexor back in the flies overexpressing the COVID-19 protein Orf6, and found that 0.2 μM Selinexor was able to attenuate the impact of Orf6.
Overall, this study shows the feasibility of using flies as a model organism to perform research on COVID-19, and as a possible host for pharmacological screen to identify putative drugs to combat COVID-19.
Citation: Zhu, J. yi, Lee, J. G., van de Leemput, J., Lee, H., & Han, Z. (2021). Functional analysis of SARS-CoV-2 proteins in Drosophila identifies Orf6-induced pathogenic effects with Selinexor as an effective treatment. Cell and Bioscience, 11(1). https://doi.org/10.1186/s13578-021-00567-8