I was browsing for recent Paul J Thornalley publications earlier, and came across this very interesting paper:
(For those not familiar with Thornalley, he is the one (and only) torch-bearer of the work surrounding quinones and methylglyoxal initiated by William F. Koch and furthered by Albert Szent-Györgyi.
Now, it is known that Pau d'Arco has the most powerful natural glyoxylase I inhibitors known: lapachol and β-lapachone. Hmmm...
(The glyoxalase system is a set of enzymes that dispose of methylglyoxal and the other reactive aldehydes that are produced as a normal part of metabolism.)
I'm not going to list the numerous benefits of Pau D'Arco, they should be known to all users of this forum. But, perhaps the most important factor behind its anticancer, antiseptic, and antimicrobial properties may very well be (beyond the NAD+ promoting effects) the inhibition of glyoxylase I...
Vulnerabilities of the SARS-Cov-2 Virus to Proteotoxicity – Opportunity for Repurposed Chemotherapy of COVID-19 Infection
(For those not familiar with Thornalley, he is the one (and only) torch-bearer of the work surrounding quinones and methylglyoxal initiated by William F. Koch and furthered by Albert Szent-Györgyi.
The global pandemic of COVID-19 disease caused by infection with the SARS-CoV-2 Coronavirus, has produced an urgent requirement and search for improved treatments whilst effective vaccines are developed. A strategy for improved drug therapy is to increase levels of endogenous reactive metabolites for selective toxicity to SARS-CoV-2 by preferential damage to the viral proteome. Key reactive metabolites producing major quantitative damage to the proteome in physiological systems are: Reactive oxygen species (ROS) and the reactive glycating agent methylglyoxal (MG); cysteine residues and arginine residues are their most susceptible targets, respectively. From sequenced-based prediction of the SARS-CoV-2 proteome, we found 0.8-fold enrichment or depletion of cysteine residues in functional domains of the viral proteome; whereas there was a 4.6-fold enrichment of arginine residues, suggesting SARS-CoV-2 is resistant to oxidative agents and sensitive to MG. We examined activated arginine residues in functional domain with predicted low pKa by neighboring group interaction in the SARS-CoV-2. We found 25 such arginine residues, including 2 in the spike protein and 10 in the nucleoprotein. These sites were partially conserved in related coronaviridae: SARS-COV and MERS. We also screened and identified drugs, which increase cellular MG concentration to virucidal levels and found two antitumor drugs with historical antiviral activity, doxorubicin and paclitaxel were the best candidate for repurposing. Our findings provide evidence of potential vulnerability of SARS-CoV2 to inactivation by MG and a scientific rationale for repurposing of doxorubicin and paclitaxel for treatment of COVID-19 disease, providing efficacy and adequate therapeutic index may be established.
Now, it is known that Pau d'Arco has the most powerful natural glyoxylase I inhibitors known: lapachol and β-lapachone. Hmmm...
(The glyoxalase system is a set of enzymes that dispose of methylglyoxal and the other reactive aldehydes that are produced as a normal part of metabolism.)
I'm not going to list the numerous benefits of Pau D'Arco, they should be known to all users of this forum. But, perhaps the most important factor behind its anticancer, antiseptic, and antimicrobial properties may very well be (beyond the NAD+ promoting effects) the inhibition of glyoxylase I...