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.
【저자키워드】 Drug repurposing, SARS-CoV-2, Bromelain, Acetylcysteine, BromAc, 【초록키워드】 Treatment, coronavirus, spike, SARS-COV-2 infection, spike glycoprotein, Infection, ACE2 receptor, nasal, in vitro, severe acute respiratory syndrome Coronavirus, virus, Culture, inactivation, clinical, Patient, Bromelain, Acetylcysteine, envelope protein, glycoprotein, virus culture, Glycoproteins, respiratory, nasal mucosa, binding, therapeutic options, Disulfide, administration, recombinant, disulfide bond, host cells, host cell, synergistic action, acute respiratory syndrome, acute respiratory syndrome coronavirus, worldwide pandemic, wild-type, clinical testing, SARS-CoV-2 protein, breakage, envelope proteins, spike mutants, synergistic, reduced, determine, demonstrated, reduce, glycosidic, 【제목키워드】 Acetylcysteine,