The –1 ribosomal frameshifting is vital for the translation of the open reading frame (ORF)1b in SARS-CoV-2. The products of ORF1b participate in viral replication. Therefore, changing the frameshift frequency reduces the survival of the virus. This study aimed to successfully develop a toolkit for screening antiviral drugs. Finally, the FDA-approved drug library was screened, revealing that ivacaftor and (–)-Huperzine A worked well in changing the –1 ribosomal frameshifting of SARS-CoV-2 in vitro .

Apelin acts as a tumor promoter in multiple malignant tumors; however, its regulatory mechanism remains unclear. Previous studies have indicated that exosomes are pivotal to mediating tumor progression and metastasis. This study examined whether apelin enhances proliferation and invasion ability of lung cancer cells via exosomal miRNA. Lung cancer A549 cells overexpressing apelin and control vector were generated by lentiviral transfection. Exosomes were isolated from the culture supernatant of each cell group, and characterized. A-exo and V-exo were respectively co-cultured with A549 cells, and assays of proliferation, apoptosis, colony formation, and invasion were conducted. Exosomal microRNA (miRNA) sequencing (miRNA-seq) was performed on A-exo and V-exo to select a candidate miRNA. It was found that A549 cells absorbed more A-exo than V-exo, and A-exo could promote proliferation, colony formation, migration and invasion of A549 cells more than V-exo. Exosomal miRNA-seq data revealed that miR-15a-5p was markedly lower in A-exo compared with V-exo. Low expression of miR-15a-5p was also found in lung cancer tissues and cell lines, suggesting that miR-15a-5p may have an anti-tumor role. Overexpression of miR-15a-5p in A549 cells was associated with less cell proliferation, migration, invasion, and suppressed cell cycle; and lower amounts of CDCA4 (cell division cycle-associated protein 4) indicated that it may be a potential target for miR-15a-5p. This study elucidated a novel regulatory mechanism that apelin may promote proliferation and invasion of lung cancer cells by inhibiting miR-15a-5p encapsulated in exosomes.

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