Abstract

The global pandemic caused by SARS-CoV-2 requires new lines of treatment to hinder viral entry and pathogenesis. Lucilia cuprina maggots’ excretion/secretion (E/S) contains proteases and antioxidants, among other active ingredients that contribute to its antibacterial, antifungal, and antiviral activity. This study aims to assess the potential effects of E/S on the entry and molecular pathogenesis of a SARS-CoV-2 isolate “NRC-03-nhCoV” in vitro for the first time. E/S was obtained from the collected maggots of L. cuprina that were maintained under controlled laboratory conditions. The E/S was used to treat VERO-E6 cells infected with SARS-CoV-2. The predicted antiviral activity of the E/S and the expression of the Notch pathway and viral pathogenesis-related genes were assessed at three time points. E/S showed potential antiviral activity against SARS-CoV-2 (IC50 = 0.324 µg/ml) with a high selectivity index value (SI = 572.997). Serine protease present in E/S was predicted to interact with transmembrane protease, serine 2 and cathepsin B. E/S was able to significantly downregulate Notch-related genes, SUMO1, and TDG in SARS-CoV-2-infected cells, shifting their expression toward levels of the control. Therefore, E/S of L. cuprina maggots is a potential strong inhibitor for SARS-CoV-2.

Key words: SARS-CoV-2; TEMPRSS2; Cathepsin B; Notch pathway; Lucilia cuprina maggots; excretion/secretion