A novel treatment of bromelain and acetylcysteine (BromAc) in patients with peritoneal mucinous tumours: A phase I first in man study

Valle, Sarah J.; Akhter, Javed; Mekkawy, Ahmed H.; Lodh, Suhrid; Pillai, Krishna; Badar, Samina; Glenn, Derek; Power, M.; Liauw, Winston; Morris, David L.

doi:10.1016/j.ejso.2019.10.033

Cited by 36 publications

(41 citation statements)

References 17 publications

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“…This property has been widely exploited in the development of several therapies (chronic obstructive pulmonary disease, allergic airways diseases, cystic fibrosis, pseudomyxoma peritonei, etc.) [20,[23][24][25][26][27]. More recently, Acetylcysteine has been used in the development of therapies for respiratory infections such as influenza and COVID-19 [28][29][30], where the integrity of the spike protein is vital for infection [12,13].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the association of the spike and envelope proteins by their respective triple cysteine motifs warrants the hypothesis of impacting virion stability following disulfide bridge disruption by the action of Acetylcysteine [18]. The combination of Bromelain and Acetylcysteine (BromAc) exhibits a synergistic mucolytic effect that is used in the treatment of mucinous tumors [19,20] and as a chemosensitizer of several anticancer drugs [21]. These different actions are due to the ability of BromAc to unfold the molecular structures of complex glycoproteins, thus allowing binding to occur because of the high affinity between RBD and ACE2.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Akhter

Quéromès

Pillai³

et al. 2021

Viruses

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show abstract

“…Research into less invasive options may aid in managing patients who are not suitable for surgery, particularly those with recurrent disease. The synergistic effects of bromelain and acetylcysteine (BromAc®) have been investigated in in vitro and in vivo formulation studies and recently in a Phase I trial for inoperable peritoneal mucinous disease, with positive results and an acceptable safety profile [7, 8]. Bromelain is a pineapple stem extract that offers certain anti-cancer properties such as interfering with malignant cell growth and other anti-inflammatory effects [9].…”

Section: Introductionmentioning

confidence: 99%

Novel Use of Bromelain and Acetylcysteine (BromAc®) for Pleural Involvement in Pseudomyxoma Peritonei

et al. 2021

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Pseudomyxoma peritonei (PMP) is a rare mucinous disease most commonly arising from the appendix. Pleural involvement arising from established PMP is seen in a small number of cases. Combined cytoreductive surgery and hyperthermic intrathoracic chemotherapy is the treatment of choice when managing intra-thoracic PMP. In cases of recurrence, surgical intervention may be technically challenging and carry higher rates of complications, morbidity, and mortality. Bromelain and acetylcysteine (BromAc<sup>®</sup>) is a novel treatment modality that has demonstrated mucolytic properties. When injected directly into mucinous disease, it facilitates tumour dissolution and allows it to be aspirated. It has recently been tested in the treatment of inoperable peritoneal mucinous disease, with an acceptable safety profile and positive objective response. Here we describe the first two cases of BromAc<sup>®</sup> administered directly into pleural adenomucinosis, with striking differences in response between the two patients likely due to differences in tumour hardness.

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“…Most importantly, Acetylcysteine reduces disulfide bonds (9). The combination of Bromelain with Acetylcysteine (BromAc) exhibits a synergistic mucolytic effect to treat mucinous tumors (10,11) and as a chemosensitizer of several anticancer drugs (12). These different actions are due to the ability of BromAc to disintegrate molecular structures of complex glycoproteins.…”

Section: Introductionmentioning

confidence: 99%

The combination of Bromelain and Acetylcysteine (BromAc) synergistically inactivates SARS-CoV-2

Akhter

Quéromès

Pillai³

et al. 2020

Preprint

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ObjectivesSARS-CoV-2 infection is the cause of a worldwide pandemic, currently with limited therapeutic options. It is characterised by being highly contagious and nasal mucosa appears to be the primary site with subsequent spread to the lungs and elsewhere. BromAc (Bromelain & Acetylcysteine) has been described to disrupt glycoproteins by the synchronous breakage of glycosidic linkages and disulphide bonds. The spike protein of SARS-CoV-2 is an attractive target as it is essential for binding to the ACE2 receptor in host cells and is formed of glycoprotein and disulphide bridges for stabilisation. Hence, we sought to determine whether BromAc has activity on the spike and envelope protein specific to SARS-CoV-2 virus.DesignGel electrophoresis analysis was carried out on recombinant spike and envelope proteins that were treated with a range of concentrations of single agents and BromAc. For UV analysis of disulfide bonds reduction, both spike and envelope protein were treated with Acetylcysteine with the determination of loss of disulfide bonds.ResultsRecombinant spike and envelope SARS-CoV-2 protein were fragmented by BromAc whilst single agents had minimal effect. Spike and envelope proteins disulphide bonds were reduced by Acetylcysteine.ConclusionBromAc disintegrates the spike and envelope protein from SARS-CoV-2 and may render it non-infective. In vitro tests on live virus have been encouraging and clinical testing through nasal administration in patients with early SARS-CoV-2 infection is imminent.

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A novel treatment of bromelain and acetylcysteine (BromAc) in patients with peritoneal mucinous tumours: A phase I first in man study

Cited by 36 publications

References 17 publications

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

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

Novel Use of Bromelain and Acetylcysteine (BromAc®) for Pleural Involvement in Pseudomyxoma Peritonei

The combination of Bromelain and Acetylcysteine (BromAc) synergistically inactivates SARS-CoV-2

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