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

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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: 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


What is known?

Prof. Stephen Elledge research team has shown that interferon-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: 

PTC299 [(4-chlorophenyl) (1S)-6-chloro-1-(4-methoxyphenyl)-1,3,4,9-tetrahydropyrido[3,4-b]indole-2-carboxylate] is an oral investigational anti-cancer drug that has been shown to inhibit the expression of VEGF [Vascular endothelial growth factor] and DHODH [(Dihydrorotate dehydrogenase]. By inhibiting the function of VEGF, it blocks angiogenesis and inhibits metastasis, while by inhibiting DHODH, a rate-limiting enzyme in Pyrimidine synthesis, it blocks pyrimidine synthesis. It has recently been shown to protect against infections caused by RNA viruses, such as SARS-COV-2, HCV, poliovirus, Ebola, and Rift Valley fever virus and others. However, its mechanism of action remains largely elusive. 

PTC299 |CAS:1256565-36-2 Probechem Biochemicals

PTC299 [(4-chlorophenyl) (1S)-6-chloro-1-(4-methoxyphenyl)-1,3,4,9-tetrahydropyrido[3,4-b]indole-2-carboxylate

This study suggests, for the first time, that PTC299, with detailed mechanistic insights, can be used to treat COVID-19 [caused by SARS-COV-2 virus) and other infectious diseases (Fig.1). PTC299, by decreasing the expression of its target genes, it could increase the expression of IFN (Interferon)-alpha/alpha-2/beta/gamma/lamda, interferon-inducible transmembrane protein IFITM3, Interferon-stimulated gene-15, Mx2,  antimicrobial peptides  and others (Figs.1-4). 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, PTC299 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 PTC299 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, Interferon-stimulated gene 15, Mx2, and others.

 

This image has an empty alt attribute; its file name is PTC299-protects-against-COVID-19.jpg-b-770x433.jpg

Figure 2 What is PTC299 and how does it function as a broad-spectrum anti-infective agent: PTC299, an experimental oral cancer drug, functions as an inhibitor of VEGF (Vascular endothelial growth factor) and DHODH (Dihydrorotate dehydrogenase: a critical enzyme in Pyrimidine synthesis). In general, PTC299, by functioning as an inhibitor of RNA replication and synthesis, it could inhibit the production of RNA viruses. More specifically, PTC299, by inducing the expression of its target immune genes, such as 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.

 

This image has an empty alt attribute; its file name is PTC299-protects-against-COVID-19.jpg-c-770x433.jpg

Figure 3 Mechanistic insight into how PTC299 functions as a broad-spectrum anti-infective agent. PTC299 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 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 PTC299 functions as a broad-spectrum anti-infective agent. PTC299 inhibits SARS-COV-2/COVID-19 viruses production through induction of its target genes, such as 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.  PTC299-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 “PTC299 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, 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

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

Web: http://genomediscovery.org

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