Bromelain Inhibits SARS-CoV-2 Infection in VeroE6 Cells

Sagar, S.; Rathinavel, A. K.; Lutz, W. E.; Struble, L. R.; Khurana, S.; Schnaubelt, A. T.; Mishra, N. K.; Guda, C.; Broadhurst, M. J.; Reid, S. P.; Bayles, K. W.; Borgstahl, G. E. O.; Radhakrishnan, P.

doi:10.1101/2020.09.16.297366

bioRxiv · 10.1101/2020.09.16.297366

Bromelain Inhibits SARS-CoV-2 Infection in VeroE6 Cells

Sagar, S.·Rathinavel, A. K.·Lutz, W. E.·Struble, L. R.·Khurana, S.·Schnaubelt, A. T.·Mishra, N. K.·Guda, C.·Broadhurst, M. J.·Reid, S. P.·Bayles, K. W.·Borgstahl, G. E. O.·Radhakrishnan, P.

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Abstract

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The initial interaction between Transmembrane Serine Protease 2 (TMPRSS2) primed SARS-CoV-2 spike (S) protein and host cell receptor angiotensin-converting enzyme 2 (ACE-2) is a pre-requisite step for this novel coronavirus pathogenesis. Here, we expressed a GFP-tagged SARS-CoV-2 S-Ectodomain in Tni insect cells. That contained sialic acid-enriched N- and O-glycans. Surface resonance plasmon (SPR) and Luminex assay showed that the purified S-Ectodomain binding to human ACE-2 and immunoreactivity with COVID-19 positive samples. We demonstrate that bromelain (isolated from pineapple stem and used as a dietary supplement) treatment diminishes the expression of ACE-2 and TMPRSS2 in VeroE6 cells and dramatically lowers the expression of S-Ectodomain. Importantly, bromelain treatment reduced the interaction between S-Ectodomain and VeroE6 cells. Most importantly, bromelain treatment significantly diminished the SARS-CoV-2 infection in VeroE6 cells. Altogether, our results suggest that bromelain or bromelain rich pineapple stem may be used as an antiviral against COVID-19. Highlights O_FIG O_LINKSMALLFIG WIDTH=178 HEIGHT=200 SRC="FIGDIR/small/297366v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@b7afb0org.highwire.dtl.DTLVardef@16f8185org.highwire.dtl.DTLVardef@1a07df8org.highwire.dtl.DTLVardef@1ae33fa_HPS_FORMAT_FIGEXP M_FIG C_FIG O_LIBromelain inhibits / cleaves the expression of ACE-2 and TMPRSS2 C_LIO_LIBromelain cleaves / degrades SARS-CoV-2 spike protein C_LIO_LIBromelain inhibits S-Ectodomain binding and SARS-CoV-2 infection C_LI

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Sagar, S., Rathinavel, A. K., Lutz, W. E., Struble, L. R., Khurana, S., Schnaubelt, A. T., Mishra, N. K., Guda, C., Broadhurst, M. J., Reid, S. P., Bayles, K. W., Borgstahl, G. E. O., Radhakrishnan, P.. 2020-09-16. Bromelain Inhibits SARS-CoV-2 Infection in VeroE6 Cells. https://doi.org/10.1101/2020.09.16.297366

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