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

ABSTRACT
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.
CONCLUSIONS
There is currently no suitable therapeutic treatment for early SARS-CoV-2 aimed at preventing disease progression. BromAc is under clinical development by the authors for mucinous cancers due to its ability to alter complex glycoprotein structures. The potential of BromAc on SARS-CoV-2 spike and envelope proteins stabilized by disulfide bonds was examined and found to induce the unfolding of recombinant spike and envelope proteins by reducing disulfide stabilizer bridges. BromAc also showed an inhibitory effecton wild-type and spike mutant SARS-CoV-2 by inactivation of its replication capacity in vitro. Hence, BromAc may be an effective therapeutic agent for early SARS-CoV-2infection, despite mutations, and even have potential as a prophylactic in people at high risk of infection.
CITATION
(Mekkawy, et.al., 2021). Research Gate: The Combination of Bromelain and Acetylcysteine (BromAc) Synergistically Inactivates SARS-CoV-2. Retrieved on01/17/23 online from https://www.researchgate.net/publication/349850528_The_Combination_of_Bromelain_and_Acetylcysteine_BromAc_Synergistically_Inactivates_SARS-CoV-2
Authors: Ahmed Mekkawy, Javed Akhter, Grégory Quéromès, Krishna Pillai, Vahan Kepenekian, Samina Badar, Emilie Frobert, Sarah Valle, David Lawson Morris.

