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. ### Competing Interest Statement The University of Valencia has filed a patent application related to the use of Ethynylestradiol to increase viral growth.