Researchers report aminoadamantanes that block SARS-CoV-2 infection by S-nitrosylation of the host ACE2 protein NaturePortfolio scrippsresearch infection coronavirus covid COVID19 protein ACE2
By Neha MathurOct 3 2022Reviewed by Danielle Ellis, B.Sc. In a recent study published in Nature Chemical Biology, researchers investigated the use of aminoadamantane nitrate compounds as anti-severe acute respiratory syndrome coronavirus 2 drugs.
Intriguingly, anecdotal reports suggest that aminoadamantane drugs offer some efficacy against SARS-CoV-2. NO-based therapies have also shown promise in human clinical trials for COVID-19 treatment. However, definitive data supporting these are lacking. The team tested the efficacy of memantine/NMT1, amantadine/NMT4, and other aminoadamantane nitrate compounds, NMT2, NMT3, and NMT5-NMT9 in a masked manner against live SARS-CoV-2 in HeLa-ACE2 cells to determine their therapeutic potential based on the selectivity index . As positive controls, they used remdesivir, apilimod, and puromycin. SI compares a compound’s half-maximal non-specific cytotoxicity in the absence of infection to its half-maximal effective antiviral concentration .
Study findings The study findings evidenced that ACE2, the cellular receptor of SARS-CoV-2 S, could be S-nitrosylated by the NO donor and transnitrosylating agent S-nitrosocysteine . This nitrosylation reaction appeared to inhibit SARS-CoV-2 entry, infectivity, and cytotoxicity. Site-directed mutagenesis confirmed that C261A/C498A mutation significantly inhibited SNOC-mediated S-nitrosylation on biotin switch assays, and MS confirmed the presence of S-nitrosylated ACE2 at Cys261 and Cys498.
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