Viruses · 2021 · 39 citations · 43 references
Viral PathogenesisImmunologyAntiviral DrugViral Structural ProteinChemical BiologyCovid-19Antiviral Drug DevelopmentSpike GlycoproteinDisulfide BondsDisulfide BridgesAllergyBiochemistryVirologyAntiviral CompoundBiomolecular EngineeringNatural SciencesAntiviral ResponseAntiviral TherapyMedicine
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.
43
Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation
Daniel Wrapp, Nianshuang Wang, Kizzmekia S. Corbett et al. · Science · 2020 · 9.7K citations · Full text
Bette Korber, Will Fischer, S. Gnanakaran et al. · Cell · 2020 · 4.4K citations · Full text
Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates
Edward E. Walsh, Robert W. Frenck, Ann R. Falsey et al. · New England Journal of Medicine · 2020 · 2.7K citations · Full text
Pedro M. Folegatti, Katie Ewer, Parvinder K. Aley et al. · The Lancet · 2020 · 2.6K citations · Full text