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

Sagar, Satish; Rathinavel, Ashok Kumar; Lutz, William E.; Struble, Lucas R.; Khurana, Surender; Schnaubelt, Andy; Mishra, Nitish K.; Guda, Chittibabu; Palermo, Nicholas Y.; Broadhurst, M. Jana; Hoffmann, Tobias; Bayles, Kenneth W.; Reid, St Patrick; Borgstahl, Gloria E. O.; Radhakrishnan, Prakash

doi:10.1002/ctm2.281

Cited by 28 publications

(22 citation statements)

References 10 publications

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“…Akhter et al [228] found that bromelain used alone (50 and 100 µg/mL) and in combination with acetylcysteine (50 and 100 µg/20 mg/mL) can disrupt the integrity of spike and envelope proteins of the SARS-CoV-2 virus. Bromelain pre-treatment significantly blocked SARS-CoV-2 viral binding in VeroE6 cells and, as a result, reduced the viral infection and SARS-CoV-2 viral RNA copies inside the cells [226]. Similarly, when bromelain's multipotent enzymatic competencies were complemented with acetylcysteine's strong power to reduce disulfide bonds, inhibition of the infectivity of SARS-CoV-2 was observed [228].…”

Section: Possible Management Of Bromelain In Covid-19 Disease Treatmentmentioning

confidence: 98%

“…ACE2 and TMPRSS2 contain cysteine residues with disulfide bonds to stabilize the protein structure [225,226]. Moreover, the spike glycoprotein and envelope protein of SARS-CoV-2 contain disulfide bridges for stabilization, and they are essential for binding to the ACE2 receptor in host cells [220,227].…”

Section: Possible Management Of Bromelain In Covid-19 Disease Treatmentmentioning

confidence: 99%

“…Thus, disulfide bonds represent an attractive target for bromelain, a cysteine protease capable of breaking disulfide bonds and degrading proteins. Sagar et al (2021) [226] found that bromelain can inhibit SARS-CoV-2 infection via targeting ACE2, TMPRSS2, and SARS-CoV-2 S-protein. Bromelain induced a dose-and time-dependent reduction in ACE2 and TMPRSS2 expression in VeroE6 cells.…”

Section: Possible Management Of Bromelain In Covid-19 Disease Treatmentmentioning

confidence: 99%

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Beneficial Properties of Bromelain

Hikisz

Bernasińska-Słomczewska

2021

Nutrients

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Bromelain is a major sulfhydryl proteolytic enzyme found in pineapple plants, having multiple activities in many areas of medicine. Due to its low toxicity, high efficiency, high availability, and relative simplicity of acquisition, it is the object of inexhaustible interest of scientists. This review summarizes scientific reports concerning the possible application of bromelain in treating cardiovascular diseases, blood coagulation and fibrinolysis disorders, infectious diseases, inflammation-associated diseases, and many types of cancer. However, for the proper application of such multi-action activities of bromelain, further exploration of the mechanism of its action is needed. It is supposed that the anti-viral, anti-inflammatory, cardioprotective and anti-coagulatory activity of bromelain may become a complementary therapy for COVID-19 and post-COVID-19 patients. During the irrepressible spread of novel variants of the SARS-CoV-2 virus, such beneficial properties of this biomolecule might help prevent escalation and the progression of the COVID-19 disease.

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Section: Possible Management Of Bromelain In Covid-19 Disease Treatmentmentioning

confidence: 98%

Section: Possible Management Of Bromelain In Covid-19 Disease Treatmentmentioning

confidence: 99%

Section: Possible Management Of Bromelain In Covid-19 Disease Treatmentmentioning

confidence: 99%

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Beneficial Properties of Bromelain

Hikisz

Bernasińska-Słomczewska

2021

Nutrients

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“…Interestingly, the reduction of ACE2 disulfide bonds also induced a decrease in binding [8]. Moreover, other reports suggested that Bromelain alone could inhibit SARS-CoV-2 infection in VeroE6 cells through an action on disulfide links [39,40]. As such, the loss of SARS-CoV-2 infectivity observed after pre-treatment with BromAc could be correlated to the cumulative unfolding of the spike and envelope proteins, with a significant reduction of their disulfide bonds by Acetylcysteine, demonstrated in vitro.…”

Section: Discussionmentioning

confidence: 90%

The Combination of Bromelain and Acetylcysteine (BromAc) Synergistically Inactivates SARS-CoV-2

Akhter

Quéromès

Pillai³

et al. 2021

Viruses

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Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is the cause of a worldwide pandemic, currently with limited therapeutic options. The spike glycoprotein and envelope protein of SARS-CoV-2, containing disulfide bridges for stabilization, represent an attractive target as they are essential for binding to the ACE2 receptor in host cells present in the nasal mucosa. Bromelain and Acetylcysteine (BromAc) has synergistic action against glycoproteins by breakage of glycosidic linkages and disulfide bonds. We sought to determine the effect of BromAc on the spike and envelope proteins and its potential to reduce infectivity in host cells. Recombinant spike and envelope SARS-CoV-2 proteins were disrupted by BromAc. Spike and envelope protein disulfide bonds were reduced by Acetylcysteine. In in vitro whole virus culture of both wild-type and spike mutants, SARS-CoV-2 demonstrated a concentration-dependent inactivation from BromAc treatment but not from single agents. Clinical testing through nasal administration in patients with early SARS-CoV-2 infection is imminent.

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“…6. Sagar et.al reported that Bromelain reduced the expression of TMPRSS2 in Calu-3 and ACE-2 negative normal bronchial epithelial (BEAS-2B) and lung adenocarcinoma (A549) cells [136].…”

Section: Akhter Etal Through Their Experiments Reported That Acetylcysteine Was Able To Reduce Onlymentioning

confidence: 99%

Combinations of drugs might increase the survival chances of COVID-19 patients: Literature review till date

Karthik¹

2021

Preprint

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

Cited by 28 publications

References 10 publications

Beneficial Properties of Bromelain

Beneficial Properties of Bromelain

The Combination of Bromelain and Acetylcysteine (BromAc) Synergistically Inactivates SARS-CoV-2

Combinations of drugs might increase the survival chances of COVID-19 patients: Literature review till date

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