| The COVID-19 epidemic caused by SARS-CoV-2 has caused a continuous global pandemic,and currently,there is no specific medicine for COVID-19.At the beginning of the outbreak,traditional Chinese medicine(TCM)played a vital role in COVID-19 clinical treatment in China.However,the components of TCM are complex and diverse,and some Chinese medicine prescriptions may.contain toxic.and harmful ingredients.The isolation and identification of the monomeric compounds with antiviral effects is of great significance for understanding the antiviral mechanism of TCM and its further clinical applications.Based on the pangolin coronavirus GX_P2V,which is highly homologous to SARS-CoV-2,our study established an efficient and reliable SARS-CoV-2 drug screening alternative model.Based on this model,8 kinds of anti-GX_P2V active monomer compounds with EC50 at the μM level were identified from the anti-COVID-19 Chinese medicine monomer library.The results of Time of addition assay and Western blot demonstrated that most of these 8 drugs played a role at the post-entry stage,which laid the foundation for further research on the anti-SARS-CoV-2 mechanism of these drugs.Moreover,the SARS-CoV-2 model was used to verify the antiviral effects of these compounds,and their EC50 of anti-SARS-CoV-2 were also at the μM level.These results further proved the effectiveness and reliability of the GX_P2V as an ideal alternative SARS-CoV-2 drug screening model.In addition,this study also predicted the potential targets of these drugs through surface plasmon resonance technology and molecular docking.In this study,8 kinds of antiviral active monomer compounds in traditional Chinese medicine prescriptions were found at the cellular level,and their antiviral action mechanism was preliminarily verified,providing new opportunities for the prevention and treatment of COVID-19. |