cuprous iodide particles

This post is not about how Mitosynergy and BDLbiochem learned of this project.  This post is about some of the crazy stuff going on in trying to find better ways to treat Covid-19.  Many of the treatments proposed to be encapsulated in this nanoparticles are already losing favor.

Laboratory Investigation of Effectiveness of Microencapsulated Biocontrol Antagonist Therapy and Immunogenicity Treatment for COVID-19 Virus

Alternate Title:

Investigation of Enhanced Experimental Nasal Muscosa Biocontrol Therapy and Immunogenicity Treatment for MERS, SARS, COV-2, (Corona-19), COVID-19 Viruses Using Nanoscopic Biopolymer/Biometal Micro-NanoCapsules With CuI Copper(I) iodide, Neocuproine Copper(II), Bathocuproine Disulfonic Acid Copper(I), Chloroquine, CBD and ACE-2 Inhibitors as Combined Functioning Antagonists

What is still not clear is if the core contents are actually part of the CuI matrix on the outside.  Many of the proposed delivery drugs have nitrogens that may form complexes with cuprous and cupric copper.  Many of the proposed contents are losing favor for the treatment of Covid-19.

Resnick_5
Cuprous iodide forms polymers with a variety of phases. The Resnick group proposed have CBD a one of the materials in the core.

Medications used to treat parasitic infections

Melarsoprol is an acute toxin  that is  under investigation in clinical trial NCT00330148 (Randomized Clinical Trial of Three Drug Combinations for Late-Stage Gambiense Human African Trypanosomiasis).  This compound is very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]   While melarsoprol is used to treat Trypanosoma brucei, the causative agent of sleeping sickness, it only worsens co-infections with  human immunodeficiency virus (HIV).  This  drug stimulates the replication of several strains of HIV-1 in monocyte-derived DCs, and also renders such cells susceptible to HIV-2 infection.   We do not know how this  drug will also increase the efficacy of the reverse transcription process in COVID-19 [1].

Resnick_3
Melansoprol is a highly toxic arenite. Eflornithine is a suicide inhibitor of ornithine decarboxylase. The structure of ornithine is also shown. An arrow points to the carboxyl group that is removed.

Eflornithine is a difluoromethylated ornithine (DFMO) compound with antineoplastic activity. Eflornithine irreversibly inhibits ornithine decarboxylase, an enzyme required for polyamine biosynthesis, thereby inhibiting the formation and proliferation of tumor cells.  DFMO has been shown to slow the replication of certain RNA viruses in a cell culture model [2].

Copper Chelators

Resnick_1
Structures of neo- and bathocuproine from PubChem
  • Neocuproine is a chelator that has been used to treat copper overload in cultured cells.  However the neocuproine MSDS (material safety data sheet) presents neocuproine as a highly toxic compound in the whole human.  Neocuproine is toxic when inhaled or comes in contact with the skin.  Its target organs are central nervous system, kidneys, liver, and optic nerve.
  • Bathocuproine is classified as an irritant by PubChem.  While neocuproine-Cu+ was shown to inhibit the HIV-1 protease needed to cleave the viral poly-protein into individual proteins.[3].  However Neo-Cu+  failed to inhibit HIV-1 poly-protein processing in a T helper cell line.  The authors proposed other methods of inhibition of viral replication.  While Coivd-19 also has a viral protease needed to cleave the poly-protein, we have no evidence that  inhibits the 3CL protease, or if it is possible to  achieve inhibitory concentrations by spraying this material into the lungs.  If nothing else, direct spraying into the lungs could limit the sites of side effects.

Forbes Recommended Covid-19 treatments

In April of this year hydroxychloroquine and azithromycin  were touted by Forbes Magazine as a possible Covid-19 combination treatment.

Hydroxychloroquine is an anti-malarial that may also be an irritant at the wrong dosing and route of exposure.

Azythithromax is an antibiotic that inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit of the bacterial 70S ribosome.  PubChem reports rare cases of acute liver injury.  

Resnick_4

A French study published at the end of March followed the  virologic and clinical outcomes of 11 consecutive patients hospitalized who received hydroxychloroquine (600 mg/d for 10 days) and azithromycin (500 mg day 1 and 250 mg days 2 to 5) using  previously dosing [4].  No benefit of this combination treatment was observed.  One patient had to discontinue treatment due to cardiac function abnormalities.  a subsequent study of 200 Covid-19 patients on the combination therapy or dihyrochloroquine alone revealed a greater incidence in long QT abnormalities.   And just two days of this writing, ” These medications can pathologically prolong the QT interval and lead to malignant ventricular arrhythmias such that organized guidance on QT evaluation and management strategies are important to reduce morbidity associated with the potential large-scale use.” [6]

The ACE2 inhibitor and cannabidiol

ACCE2 counter blances ACE1 in terms of maintaining blood pressure [7].  ACE2 expression may be influeced by ACE1 inhibitors [7].  In addition to the lungs, ACE2 is expressed in the brain, gut, and kidney.  The loss of ACE2 in the brain stem may facilitate an increase in sympathetic drive, alterations in the baroreflex, and exacerbation of hypertension.

Resnick_2

And finally, there is some suggestion that CBD might make Covid-19 infections worse [8].

References

  1. Barat C, Pepin J, Tremblay MJ. (2011) HIV-1 replication in monocyte-derived dendritic cells is stimulated by melarsoprol, one of the main drugs against human African trypanosomiasis. J Mol Biol. 2011 Jul 29;410(5):1052-64
  2. Mounce BC, Cesaro T, Moratorio G, Hooikaas PJ, Yakovleva A, Werneke SW, Smith EC, Poirier EZ, Simon-Loriere E, Prot M, Tamietti C, Vitry S, Volle R, Khou C, Frenkiel MP, Sakuntabhai A, Delpeyroux F, Pardigon N, Flamand M, Barba-Spaeth G, Lafon M, Denison MR, Albert ML, Vignuzzi M. (2016)Inhibition of Polyamine Biosynthesis Is a Broad-Spectrum Strategy against RNA Viruses. J Virol. 2016 Oct 14;90(21):9683-9692. [PMC free article]
  3. Davis DA, Branca AA, Pallenberg AJ, Marschner TM, Patt LM, Chatlynne LG, Humphrey RW, Yarchoan R, Levine RL. (1995)Inhibition of the human immunodeficiency virus-1 protease and human immunodeficiency virus-1 replication by bathocuproine disulfonic acid Cu1+. Arch Biochem Biophys. 322(1):127-34.
  4. Molina JM, Delaugerre C, Le Goff J, Mela-Lima B, Ponscarme D, Goldwirt L, de Castro N.(2020)No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection. Med Mal Infect. 2020 Jun;50(4):384. [PMC free article]
  5. Saleh M, Gabriels J, Chang D, Kim BS, Mansoor A, Mahmood E, Makker P, Ismail H, Goldner B, Willner J, Beldner S, Mitra R, John R, Chinitz J, Skipitaris N, Mountantonakis S, Epstein LM.(2020 Apr 29) The Effect of Chloroquine, Hydroxychloroquine and Azithromycin on the Corrected QT Interval in Patients with SARS-CoV-2 Infection. Circ Arrhythm Electrophysiol.
  6. Asensio E, Acunzo R, Uribe W, Saad EB, Sáenz LC.(2020) Recommendations for the measurement of the QT interval during the use of drugs for COVID-19 infection treatment. Updatable in accordance with the availability of new evidence. J Interv Card Electrophysiol. 2020 May 16
  7. South AM, Diz DI, Chappell MC. (2020) COVID-19, ACE2, and the cardiovascular consequences. Am J Physiol Heart Circ Physiol. 2020 May 1;318(5):H1084-H1090. doi: 10.1152/ajpheart.00217.2020. Epub 2020 Mar 31.[PMC free article]  [author pod cast]
  8. Brown JD. (2020) Cannabidiol as prophylaxis for SARS-CoV-2 and COVID-19? Unfounded claims versus potential risks of medications during the pandemic.Res Social Adm Pharm. 2020 Mar 31. pii: S1551-7411(20)30300-4. [Cross Ref]

Published by BL

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