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Biology subjects

Gadea-Salom, L.

Publications and source records attributed to Gadea-Salom, L..

2 recordsLinked to original sources

Identification of small molecules with virus growth enhancement properties

The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused the pandemic disease known as coronavirus disease 2019 (COVID-19). COVID-19 vaccines were developed at record speed and were authorized approximately a year after the original outbreak. This fast response saved the lives of countless individuals and reduced the disease burden of many more. The experience has served as a reminder of the necessity to implement solid vaccine development platforms and fast production pipelines. Manufacturing vaccines for enveloped viruses, including some SARS-CoV-2 vaccines, often relies on the production of large quantities of viruses in vitro. Thus, speeding up or increasing virus production would expedite vaccine development. With this objective in mind, we established a high throughput screening (HTS) to identify small molecules that enhance or speed up host-virus membrane fusion. Among the HTS hits, we identified that ethynylestradiol augments SARS-CoV-2 fusion activity in both the absence and presence of TMPRSS2. Furthermore, we confirmed that ethynylestradiol can boost the growth of not only SARS-CoV-2 but also Influenza A virus in vitro. A small molecule with these characteristics could be implemented to improve vaccines production. ImportanceThe (COVID-19) pandemic had a tremendous impact on our healthcare systems and the global economy. The rapid development of effective vaccines saved the lives of countless individuals and reduced the disease burden of many more. Intending to increase vaccine production, we developed and performed a high-throughput screening (HTS) to identify small molecules that enhance viral and cellular membrane fusion. Among the HTS hits, we confirmed that Ethynylestradiol can boost the growth of SARS-CoV-2 and Influenza A virus in vitro.

microbiology↗

Computational design of BclxL inhibitors that target transmembrane domain interactions

Several methods have been developed to explore interactions among water-soluble proteins or regions of proteins. However, techniques to target transmembrane domains have not been examined thoroughly. Here we developed a novel computational approach to design transmembrane sequences that specifically modulate protein-protein interactions in the membrane. To illustrate this method we demonstrated that BclxL can interact with other members of the Bcl2 family through the transmembrane domain and that these interactions are necessary for BclxL control of cell death. Next, we designed sequences that specifically recognize and sequester the transmembrane domain of BclxL. Hence, we were able to prevent BclxL intra-membrane interactions and cancel its anti-apoptotic effect. These results advance our understanding of protein-protein interactions in membranes and provide new means to modulate them. Moreover, the success of our approach may trigger the development of a new generation of inhibitors targeting interactions between transmembrane domains.

biochemistry↗