Krebs cycle–derived immunometabolite itaconate based therapy for COVID-19/SARS-COV-2 and other infectious diseases: 4-Octyl Itaconate, a cell-permeable derivative derived from the TCA cycle metabolite Aconitate, inhibits SARS-COV-2, Hepatitis-B/C, Dengue, Zika, Ebola, HIV-1, Mtb, Malaria, CMV, Influenza H1NI1, Foot and Mouth disease, ADV, respiratory syncytial, Sindbis, and SFV viruses and others by increasing the levels of NRF2, IFN (Interferon)-alpha/alpha-2/beta/gamma/lamda, interferon-inducible transmembrane protein IFITM3, Interferon-stimulated gene-15, Mx2 and antimicrobial peptides and decreasing the expression of inflammatory cytokines, 19/November/2020, 11.43 am

PTC299-based therapy for COVID-19/SARS-COV-2 and other infectious diseases: PTC299, an anti-cancer drug, inhibits SARS-COV-2, Hepatitis-B/C, Dengue, Zika, Ebola, HIV-1, Mtb, Malaria, CMV, Influenza H1NI1,  Foot and Mouth disease, ADV, respiratory syncytial, Sindbis, and SFV viruses and others by increasing the levels of IFN (Interferon)-alpha/alpha-2/beta/gamma/lamda, interferon-inducible transmembrane protein IFITM3, Interferon-stimulated gene-15, Mx2 and antimicrobial peptides and decreasing the expression of inflammatory cytokines 24/October/2020, 9.39 am
October 24, 2020
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Introduction: What they say:

A study from the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard Medical School, Charlestown, MA 02129, USA shows that “The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus.” This study was published, in the 24 December 2009 issue of the journal “Cell” (the number 1 research journal in General Biology with an impact factor of 33), by the 2015 Laskar award winner Prof. Stephen Elledge, Brass and others.


What we say: 

On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Krebs cycle–derived immunometabolite itaconate based therapy for COVID-19/SARS-COV-2 and other infectious diseases: 4-Octyl Itaconate, a cell-permeable derivative derived from the TCA cycle metabolite Aconitate, inhibits SARS-COV-2, Hepatitis-B/C, Dengue, Zika, Ebola, HIV-1, Mtb, Malaria, CMV, Influenza H1NI1,  Foot and Mouth disease, ADV, respiratory syncytial, Sindbis, and SFV viruses and others by increasing the levels of NRF2, IFN (Interferon)-alpha/alpha-2/beta/gamma/lamda, interferon-inducible transmembrane protein IFITM3, Interferon-stimulated gene-15, Mx2 and antimicrobial peptides and decreasing the expression of inflammatory cytokines


What is known?

Prof. Stephen Elledgeresearch team has shown thatinterferon-inducible transmembrane proteins IFITM1, 2, and 3 inhibit influenza A H1N1 virus, West Nile virus, and dengue virus replication, suggesting that increasing the expression of IFITM3 may confer resistance against these viruses. Other studies suggest that IFITM3 may also protect against Ebola virus, hepatitis C virus, yellow fever virus and SARS coronavirus etc.


From research findings to therapeutic opportunity: 

4-Octyl Itaconate [(2-Methylenesuccinic acid/2-Methylidenebutanedioic acid] is a cell-permeable derivative of Itaconate, which can be derived from TCA cycle metabolite aconitate.

This study suggests, for the first time, that 4-Octyl Itaconate, with detailed mechanistic insights, can be used to treat COVID-19 [caused by SARS-COV-2 virus) and other infectious diseases (Fig.1). 4-Octyl Itaconate, by decreasing the expression of its target genes, it could increase the expression of NRF2, IFN (Interferon)-alpha/alpha-2/beta/gamma/lamda, interferon-inducible transmembrane protein IFITM3, Interferon-stimulated gene-15, Mx2,  antimicrobial peptides (CAMP, DEF4A and others) and others (Figs.1-4), while decreasing the expression of NLRP3, IL-1β, hypoxia-inducing factors and others. Thereby, it could: (1) inhibit/prevent the entry/fusion/replication/production of  SARS-COV-2, SARS-COV-1, Hepatitis-B/C, Dengue, Zika, Ebola, HIV-1, Mtb, Malaria, CMV, Influenza H1NI1,  Foot and Mouth disease, ADV, respiratory syncytial,  Sindbis, and SFV viruses; (2) confer resistance against infection caused by SARS-COV-2, SARS-COV-1, Hepatitis-B/C, Dengue, Zika, Ebola, HIV-1, Mtb, Malaria, CMV, Foot and Mouth disease, ADV, Influenza H1NI1,  respiratory syncytial,  Sindbis, and SFV viruses; and (3) promote innate immunity (Figs. 1-6)

Furthermore, 4-Octyl Itaconate could protect against clinical complications, such as acute respiratory distress syndrome, cytokine storm and others, caused by SARS-COV-2 and other viruses. 

Figure 1. Mechanistic insight into how 4-Octyl Itaconate prevents/protects against SARS-COV-2. PTC299 inhibits SARS-COV-2 &  SARS-COV-1 through induction of its target genes, such as IFN (Interferon)-alpah/alpha-2/beta/gamma/lamda, antiviral Proteins IFITM3/2/1, Interferon-stimulated gene 15, Mx2, and others.
Figure 2 What is 4-Octyl Itaconate and how does it function as a broad-spectrum anti-infective agent: 4-Octyl Itaconate, a cell-permeable TCA cycle-derived metabolite, which can be derived from the TCA cycle metabolite aconitate. 4-Octyl Itaconate, by inducing the expression of its target immune genes, such as NRF2, IFN (Interferon)-alpha/alpha-2/beta/gamma/lamda, antiviral Proteins IFITM3, Interferon-stimulated gene 15, Mx2, and others, it could inhibit SARS-COV-2 (COVID-19), SARS-COV-1, Hepatitis-B/C, Dengue, Zika, Ebola, HIV-1, Mtb, Malaria, CMV, Influenza H1NI1,  respiratory syncytial, Sindbis, Foot and Mouth disease virus, ADV, and SFV viruses production.
Figure 3 Mechanistic insight into how 4-Octyl Itaconate functions as a broad-spectrum anti-infective agent. 4-Octyl Itaconate inhibits Hepatitis-B/C, Dengue, Zika, Ebola, HIV-1, Mtb, Malaria, CMV, Influenza H1NI1,  respiratory syncytial, Sindbis, Foot and Mouth disease virus, ADV, and SFV viruses production through induction of its target genes, such as NRF2, IFN (Interferon)-alpha/alpha-2/beta/gamma/lamda, antiviral Proteins IFITM3, Interferon-stimulated gene 15, Mx2, antiviral Proteins IFITM3, Interferon-stimulated gene 15, Mx2 and others.
Figure 4 Mechanistic insight into how 4-Octyl Itaconate protects against COVID-19. 4-Octyl Itaconate inhibits SARS-COV-2/COVID-19 viruses production through induction of its target genes, such as NRF2, IFN (Interferon)-alpha/alpha-2/beta/gamma/lamda, antiviral Proteins IFITM3, Interferon-stimulated gene 15, Mx2, antiviral Proteins IFITM3, Interferon-stimulated gene 15, Mx2 and others.
Figure 5.  4-Octyl Itaconate-based therapy for COVID-19 and other infectious diseases. GBMD (genomediscovery.org) is looking for Bio-Medical Scientists/Professor/Medical faculties/Clinicians who would be interested in collaborating with us in exploring the bio-medical mechanisms and in carrying out a clinical trial.

Thus, pharmacological formulations encompassing “4-Octyl Itaconate or its derivatives or its mechanistic equivalents, either alone or in combination with other drugs/compounds, can be used to prevent/treat/protect against infections caused by SARS-COV-2, SARS-COV-1, Hepatitis-B/C, Dengue, Zika, Ebola, HIV-1, Mtb, Malaria, CMV, Foot and Mouth disease, ADV (Adenovirus), Influenza H1NI1,  respiratory syncytial,  Sindbis, and SFV viruses (Figs. 1-5).


Details of the research findings: 

Idea formulated by Dr L Boominathan PhD

Undisclosed information:

Type: Research cooperation

For more details on research cooperation, you may reach us at drboomi@genomediscovery.org 


References: 

CitationBoominathan L, Krebs cycle–derived immunometabolite itaconate based therapy for COVID-19/SARS-COV-2 and other infectious diseases: 4-Octyl Itaconate, a cell-permeable derivative derived from the TCA cycle metabolite Aconitate, inhibits SARS-COV-2, Hepatitis-B/C, Dengue, Zika, Ebola, HIV-1, Mtb, Malaria, CMV, Influenza H1NI1, Foot and Mouth disease, ADV, respiratory syncytial, Sindbis, and SFV viruses and others by increasing the levels of NRF2, IFN (Interferon)-alpha/alpha-2/beta/gamma/lamda, interferon-inducible transmembrane protein IFITM3, Interferon-stimulated gene-15, Mx2 and antimicrobial peptides and decreasing the expression of inflammatory cytokines, 19/November/2020, 11.42 am

Courtesy: When you cite drop us a line at drboomi@genomediscovery.org,  Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

Web: http://genomediscov

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