Pau D'arco (and other quinones): A Potential Silver Bullet Against Covid?

Jam

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I was browsing for recent Paul J Thornalley publications earlier, and came across this very interesting paper:

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...
 

Regina

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Micahel Yon embedded and reporting from Panama.

I was wondering if they chew pau d'arco leaves.

Also wondered if tribes were getting a deliberate spraying operation of sarscov2.
Crash local economies and bank the surviving unbanked.

And how would he learn he has "diabetes?"

 
OP
Jam

Jam

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ABSTRACT

Background: The ongoing coronavirus disease 2019 (COVID-19) pandemic has resulted in a global health emergency. With incomplete vaccination and incomplete protection of the vaccinated population, there remains an urgent need to develop drugs to treat COVID-19. Our previou in silico analysis suggested vulnerability of SARS-CoV-2 to inactivation by the endogenous reactive metabolite, methylglyoxal (MG), by modification of arginine residues in the functional domains of viral spike and nucleocapsid proteins 1–3 . In this study, the antiviral activity of MG against wild-type SARS-CoV-2 using in vitro assays was evaluated. Methods: Wild-type SARS-CoV-2 with titers of multiplicities of infection (MOI) 0.8, 0.2, 0.02, and 0.01 were incubated with 2-fold serial dilutions of MG (7.8 μM to 500 μM) in infection medium for six hour. MG-treated and untreated control SARS-CoV-2 were incubated with confluent cultures of Vero cells in vitro for one hour, cultures were washed and then incubated in a fresh infection medium at 37°C for 4 - 5 days until 70% of virus–infected cells displayed cytopathic effect (CPE). The antiviral activity of MG was judged by assessing virus replication using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and median tissue culture infectious dose (TCID50) assays. Results: MG inhibited virus replication as measured by PCR and CPE of SARS-CoV-2 in vitro, with TCID50 increasing with increasing MOI. MG was most potent at MOI 0.02 and 0.01 where EC50 of MG was 49.6 ± 4.7 μM and 28.5 ± 1.3μM; respectively. Similar findings were also found for a shorter incubation period (3 hours) of MG and virus. Conclusion: MG has inhibitory activity against wild-type SARS-CoV-2 for virus exposure in the cell-free systems at low MOI. However, the antiviral activity of MG against other SARS-CoV-2 variants including alpha- and beta-variants is being investigated. Drugs increasing cellular concentration of MG to viricidal levels may have anti-COVID-19 activity.
 
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Jam

Jam

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Abstract​

Conclusion: Manuka honey has antiviral activity against SARS-CoV-2 when incubated with the virus in cell-free media at no greater than ca. 40-fold dilutions of 250+ grade. Anti-viral activity was inhibited by AG, consistent with the anti-viral effect being mediated by MG. Manuka honey dilutions in MG equivalents had similar antiviral effect compared to authentic MG, also consistent with MG content of Manuka honey mediating the antiviral effect. Whilst Manuka honey may inactivate SARS-CoV-2 in cell-free culture medium, its antiviral activity in vivo for other than topical application may be limited because of the rapid metabolism of MG by the glyoxalase system and limited bioavailability of oral MG.
 

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