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Opunika Repurposing For Covid-19-The Scientific Basis

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Polyphenolic Extracts from Opunika® (Punica granatum)

– Repurposed for COVID19

#COVID19 #Coronavirus
Opunika®: Proven Antimalarial, now repurposed for Covid-19
Mode of Action[1]
1 Ellagic Acid and Ellagitannins in Punica granatum are
the active moieties contributing to anti plasmodial
action along with D.sylvatica

Coverage[1]
2 Plasmodium vivax and Plasmodium falciparum induced
malaria

o Derived from epicarp of Immature


Punica granatum fruit Antimalarial Activity[2]
(Chloroplast stage) Therapeutic as well as Preventive. Additionally, it also
3 has an inhibitory effect on NF-kB pathway leading to
o The selected species is different suppression of host inflammatory response, limiting the
from the commercial variety severe form of falciparum malaria
available

o Composition: each 500 mg cap:


Toxicity Profile[3]
o Punica granatum L. 90 % 4 Toxicity data on MRC-5 human diploid embryonic lung
o Diospyros Sylvatica 10 % cell show Selective Index (LD50 / IC50) of 20.2

Tolerability Profile[4]
5 Well tolerated even by Children and Pregnant ladies.
Commercially available in the market since 2013

#COVID19 #Coronavirus
Characterised with antimalarial potency validated at CCMB
150
150
CLS 01 CLS 02
CLS 04

% Inhibition
100 100
CLS 07

% Inhibition
OPU 01
50 50

0
0
0 1 2 3 -1 0 1 2 3
Inhibitor (ug/ml) Inhibitor (ug/ml)
-50

Market presence since


2013 testifying to its
safety and efficacy.

#COVID19 #Coronavirus
We Got International Recognition!

(Earlier known as Omaria-P)

5 international publications pertaining to


it’s antimalarial efficacy!

#COVID19 #Coronavirus
Punica granatum - an ideal profile as COVID-19 therapeutic agent

Anti-viral [5]

o Action on enveloped viruses well documented


o Mechanism of action covers Viral entry, Viral integrity Envelop protein
and Viral replication depending on the virus
o Antiviral action documented on RNA as well as DNA Membrane protein
viruses
Spike protein
o Reduces glycosylation of ACE receptors thereby
supplementing its direct antiviral properties Nucleocapsid protein
Enclosing RNA

Lipid membrane

Anti-inflammatory [5] SARS-CoV-2 is an enveloped virus

o Immunomodulation properties well documented by


way of action on NF-kB pathway, supressing the
cytokine proliferation
o Acts directly on MMP-9 (Matrix MetalloProtinease-9)
which promotes inflammation in airways
o Potent antioxidant action comparable to Vit-C, thereby
amplifying anti-inflammatory action

#COVID19 #Coronavirus
Opunika® (Punica granatum) -Repurposed for COVID-19
Anti-viral action of Punica granatum extracts (PgE) well documented on enveloped viruses [6]

SL# Target Mechanism Target Virus Sub-Type Polyphenolic Compound

Influenza-A H3N3 Punicalagin

Hepatitis-C Delphinidin

HIV HIV 1 Flavonoid-ECGC


01 Viral Entry Herpes Simplex Virus Type I & II Flavonoid-ECGC

Hepatitis-B Flavonoid-ECGC

Zika Flavonoid-ECGC

Influenza-A H1N1/H3N3 Phenolic acid-Gallic Acid

02 Viral Integrity Herpes Simplex Virus Type I & II Procyanidin B2

Dengue Virus DEN 2 Flavonoid-ECGC

Influenza-A H9N2 Flavonoid-ECGC


03 Viral Replication Hepatitis-B Phenolic acid-Caffeic Acid

#COVID19 #Coronavirus
Opunika® (Punica granatum) -Repurposed for COVID-19
Anti-inflammatory action of Punica granatum extracts (PgE) well documented [2][7]

Anti-inflammatory Activity Mechanism

o PgE has been found to be a rich source of antioxidants, o Severe falciparum malaria is an inflammatory cytokine driven disease.
consisting of phenolic compounds that readily donate Malaria haemozoin and TNF promote MMP-9 which accentuates the
electrons to free radicals, converting them to relatively host inflammatory response. PgE inhibit secretion of MMP-9 as well as
stable compounds NF-kB pathway driven transcription factors to limit progression to
severe form of the disease.

o Beneficial effect of PgE for the treatment of malarial o The anti-inflammatory components of PgE, i.e., punicalagin, punicalin,

disease is attributed to the anti-parasitic activity and the strictinin A and granatin B significantly inhibit the expression of pro-

inhibition of the pro-inflammatory mechanisms involved in inflammatory proteins

the onset of cerebral malaria

The synergy of Anti-viral and Anti-inflammatory action of PgE show promise in


the treatment of Covid-19.

#COVID19 #Coronavirus
Opunika® vs Hydroxychloroquine for Covid-19
Potential profile of PgE in Opunika® (compared with Hydroxychloroquine [2][5] ) show promise for ready
deployment

Postulated mechanism / Profile Hydroxychloroquine P.granatum Extracts (PgE)

Inhibition of Viral fusion at the site of host cell Disruption to virus entry through structural damage
Supported by invitro studies
membrane demonstrated against RNA and DNA viruses.

PgE have been proven in invitro and invivo studies


Suppression of viral entry through altered
Supported by invitro studies regarding reduction of glycosylation of ACE
glycosylation of ACE-2
receptors hence impairing viral entry.
Inhibition of intracellular Viral replication Viral replication inhibition in Influenza-A reassortant
Supported by invitro studies
through Endosomal pH regulation strains proved invitro studies.
Disruption of virion assembly and release Not well documented Well documented against enveloped viruses.

Potent immunomodulation through NF-kB pathway


Proven in immunomodulatory use
Immunomodulation of cytokine storm resulting in taming of the Cytokine cascade proven
such as arthritis
in P.falciparum malaria.
Good safety profile and well
Tolerability profile Good safety profile and well tolerated.
tolerated

#COVID19 #Coronavirus
Opunika® Extracts Have Been Standardized through Validation
Analytical methods developed inhouse and validated at third party labs through LC-MS-MS (Data on file)

Different cultivars of Punica granatum may yield different properties therefore require standardization through marker
compounds such as Total Phenolic content, Flavonoid content and Hydrolysable Tannin Content. Moreover, commercially
available Punica granatum does not show the desired therapeutic properties.

#COVID19 #Coronavirus
The way forward against Covid-19

We invite collaborative studies to prove the therapeutic role of Punica


granatum extracts (PgE) invitro against SARS-CoV-2 followed by
Clinical trials in Covid-19 patients

Step-1: If possible, Opunika® extracts can be tested invitro against SARS-CoV-2


at a BSL-3 facility.This would help to potentiate the formulation

Step-2: Opunika® capsules can be given in a Randomised Clinical Trial of 100


patients against a control group.The treatment approach could be
Opunika® with standard treatment compared with standard treatment
alone. Primary endpoints could be time to test negative for Covid-19 and
disease severity measured through ventilator support.

#COVID19 #Coronavirus
References
1. Dell’Agli M etal. Antiplasmodial activity of Punica granatum L. fruit rind. Jour-of-Ethno 125 (2009) pg 279-285.

2. Dell’Agli M etal. Ellagitannins of the fruit rind of pomegranate (Punica granatum) antagonize in vitro the host inflammatory response mechanisms
involved in the onset of malaria.Malaria Journal 2010,9:208

3. Lekana-Douki JB,et al. Indian Anti-Malaria OMARIA Is Effective Against African Drug Resistant P. falciparum Field Isolates and Laboratory Strains;
without Toxicity. Intl-Jour-Clin-Medi,2012,3,pg 1-8

4. Bhattacharya D. Fight malaria at home:Therapeutic and prophylaxis clinical data.Asian Pacific Journal of Tropical Disease (2011) 142-149

5. Liu C et al. Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus Diseases. ACS
Cent.Sci. 2020, https://dx.doi.org/10.1021/acscentsci.0c00272

6. Seo DJ,Choi C.Viral Disease and Use of Polyphenolic Compounds;Chapter 25,Polyphenols:Prevention and Treatment of Human
Disease,Elsevier,2018, pp 301-311

7. T. Ismail et al. / Journal of Ethnopharmacology 143 (2012) 397–405

#COVID19 #Coronavirus
Thank You

Name : Shubhendu Kumar Dash

Designation : Director (Founder), CONSYTEL

We desire a “Covid-19 free” Email : consytelbiz@gmail.com

India naturally Mobile : +91-9030739849

Works: Plot No.66-A, Phase-IV, IDA Jeedimetla, Hyderabad

R&D: Atal Innovation Centre, CCMB Annexe-2,Habsiguda,Hyderabad

#COVID19 #Coronavirus

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