Work

Bromelain inhibits SARS‐CoV‐2 infection via targeting ACE‐2, TMPRSS2, and spike protein

Year: 2021

Type: article

Abstract: Bromelain inhibits SARS-CoV-2 infection via targeting ACE-2, TMPRSS2, and spike proteinDear Editor, The new coronavirus, SARS-CoV-2, transmits rapidly from human-to-human resulting in the ongoing pandemic.SARS-CoV-2 infects angiotensin-converting enzyme 2 (ACE-2) expressing lung, heart, kidney, intestine, gall bladder, and testicular tissues of patients, leading to organ failure and sometimes death.1,2 Currently, COVID-19 patients are treated with different agents, including favilavir, remdesivir, chloroquine, hydroxychloroquine, lopinavir, darunavir, and tocilizumab.3,4 However, the safety and efficacy of those drugs against COVID-19 still need further confirmation by randomized clinical trials.Hence, there is an emergent need to repurpose the existing drugs or develop new virus-based and host-based antivirals against SARS-CoV-2.Bromelain is a cysteine protease isolated from pineapple stem and is used as a dietary supplement for treating patients with pain, inflammation, 5 thrombosis, 6 and cancer.7 Recently, studies have shown that SARS-CoV-2 homotrimeric viral spike protein (S1) binds to the Transmembrane Serine Protease 2 (TMPRSS2) primed host cell's receptor ACE-2 for initial entry, followed by S2mediated membrane fusion.8 Of several normal and cancerous cells tested, VeroE6 and Calu-3 cells showed ACE-2 protein expression (Fig. 1A), as well as a basal level of TMPRSS2 protein (Fig. 1B).Since ACE-2 9 and TMPRSS2 (UniProtKB-O15393) contains cysteine residues with disulfide bonds to stabilize the protein structure, we investigated the effect of bromelain on ACE-2 and TMPRSS2 expression.Bromelain-induced a dose-and time-dependent reduction of ACE-2 and TMPRSS2 expression in VeroE6 cells (Fig. 1C and D) but do not alter ACE-2 expression in Calu-3 cells (Fig. 1E).However, bromelain reduces the expression of TMPRSS2 in Calu-3 (Fig. 1E) and ACE-2 negative normal bronchial epithelial (BEAS-2B) and lung adenocarcinoma (A549) cells (Fig. 1F and G).Cysteine protease inhibitor (E-64) treatment further confirmed that bromelain's cysteine protease

Source: Clinical and Translational Medicine

DOI: 10.1002/ctm2.281