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

Akhter et al., Viruses, doi:10.3390/v13030425
Mar 2021  
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14th treatment shown to reduce risk in February 2021, now with p = 0.000028 from 24 studies, recognized in 3 countries.
Lower risk for mortality, hospitalization, and cases.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 112 treatments. c19early.org
In Vitro study showing dose dependent inactivation of SARS-CoV-2 with the combination of bromelain and acetylcysteine.
9 preclinical studies support the efficacy of N-acetylcysteine for COVID-19:
N-acetylcysteine shows dose-dependent inhibition of SARS-CoV-23,6,8, shows anti-inflammatory and immunomodulatory effects against SARS-CoV-2-induced immune responses in combination with bromelain5, suppressed virus-induced reactive oxygen species and blocked viral replication in a humanized mouse model and in human lung cells4, and may limit COVID-19 induced cardiac damage by boosting cellular antioxidant defenses and potentially mitigating the oxidative stress caused by spike protein-induced ROS production in cardiac fibroblasts9. NAC may be beneficial for COVID-19 by replenishing glutathione stores and reinforcing the glutathione peroxidase-4 pathway to inhibit ferroptosis, an oxidative stress-induced cell death pathway implicated in COVID-1910. NAC reinforces glutathione levels, reduces ROS, and minimizes ferroptosis and cytokine storm11.
Akhter et al., 6 Mar 2021, USA, peer-reviewed, 9 authors. Contact: david.morris@unsw.edu.au (corresponding author), javed.akhter@health.nsw.gov.au, vahan.kepenekian@chu-lyon.fr, samina.badar@unsw.edu.au, z3170073@ad.unsw.edu.au, sarah.valle@mucpharm.com, panthera6444@yahoo.com.au, gregory.queromes@univ-lyon1.fr, emilie.frobert@chu-lyon.fr.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperN-acetylcys..All
The Combination of Bromelain and Acetylcysteine (BromAc) Synergistically Inactivates SARS-CoV-2
Javed Akhter, Grégory Quéromès, Krishna Pillai, Vahan Kepenekian, Samina Badar, Ahmed H Mekkawy, Emilie Frobert, Sarah J Valle, David L Morris
Viruses, doi:10.3390/v13030425
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.
Author Contributions: Conceptualization, J.A., K.P., S.J.V., and D.L.M.; methodology, J.A., G.Q., K.P., S.B., and A.H.M.; validation, J.A., G.Q., K.P., V.K., S.B., and A.H.M.; investigation, J.A., G.Q., K.P., V.K., S.B., and A.H.M.; writing-original draft preparation, G.Q., K.P., V.K, A.H.M., E.F., and S.J.V.; supervision, D.L.M. and E.F.; project administration, S.J.V.; funding acquisition, S.J.V. and D.L.M. All authors have read and agreed to the published version of the manuscript. Conflicts of
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