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Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 utilizes its spike protein to enter host cells via ACE2 and TMPRSS2. Here, we constructed and validated spike-pseudotyped virus using lentiviral genomes to mimic SARS-CoV-2 cell entry. Findings revealed that elevated levels of ACE2 and/or TMPRSS2 enhanced infection efficiency of pseudotyped SARS-CoV-2 in recipient cells. The infection efficiency depends on TMPRSS2 transfection dosage with ACE2 overexpression. Stably overexpressed ACE2 and TMPRSS2 in 293T cells also enhanced the infection efficiency of the pseudotyped SARS-CoV-2. Finally, Osimertinib, an EGFR inhibitor, enhanced SARS-CoV-2 infection susceptibility in PC-9 cells by the potential upregulation of ACE2 levels. The research underscores the critical role of ACE2 and TMPRSS2 in SARS-CoV-2 infection and the potential implications of certain anti-cancer agents in SARS-CoV-2 susceptibility. The created pseudotyped SARS-CoV-2 will offer a valuable tool for studying the cell entry mechanism of SARS-CoV-2 and identify therapeutic strategies.