(W1329) HUMAN TROPHOBLAST CELLULAR MODEL IS HIGHLY PERMISSIVE TO SARS-COV-2 INFECTION AND ENABLES THE DISCOVERY OF ANTIVIRAL NATURAL COMPOUNDS POTENTLY AGAINST SARS-COV-2
Post-doc Centre for Translational Stem Cell Biology HONG KONG, Hong Kong
Abstract: Non-human and/or abnormal human cell lines have long been adopted for virology studies, particularly for COVID-19. However, they may not fully mimic human physiological contexts particularly those together with pregnancy and alternative models are needed. Here we utilized our previously established normal human early syncytiotrophoblast (eSTB) model for infecting with SARS-CoV-2 of different variants and assessing antivirals. The eSTBs were highly susceptible to SARS-CoV-2 infection while being more sensitive to antivirals but resistant to post-infection cell death than other conventionally used cell models. We further validated several clinically administered antivirals and revealed that Nirmatrelvir is effective, while Molnupiravir is not, which aligns with clinical manifestations. Using SARS-CoV-2 infected eSTBs, natural compound libraries were screened and potential candidates with high anti-SARS-CoV-2 functions were identified. Selective candidate nature compound effectively reduced the infection of primary human airway cells and organoids in vitro and in both mice and hamsters in vivo by SARS-CoV-2. The eSTB cellular model is an ideal platform for virology study and antiviral discovery.
Funding Source: This work was financially supported by Health@InnoHK, Innovation Technology Commission (ITC), HKSAR, China
