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Polyphenolic Extracts from Punica granatum (Opunika®)– Repurposed for COVID19

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Opunika®: Proven Antimalarial,repurposed for Covid-19

o Derived from epicarp of Immature

Punica granatum fruit

(Chloroplast stage)

o The selected species is different

from the commercial variety

available

o Composition: each 500 mg cap:

o Punica granatum L. 90 %

o Diospyros Sylvatica 10 %

1Mode of Action[1]

Ellagic Acid and Ellagitannins in Punica granatum are

the active moieties contributing to anti plasmodial

action along with D.sylvatica

2Coverage[1]

Plasmodium vivax and Plasmodium falciparum induced

malaria

5Tolerability Profile[4]

Well tolerated even by Children and Pregnant ladies.

Commercially available in the market since 2013

Antimalarial Activity[2]

Therapeutic as well as Preventive. Additionally, it also

has an inhibitory effect on NF-kB pathway leading to

suppression of host inflammatory response, limiting the

severe form of falciparum malaria

3

4Toxicity Profile[3]

Toxicity data on MRC-5 human diploid embryonic lung

cell show Selective Index (LD50 / IC50) of 20.2

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Characterised with antimalarial potency validated at CCMB

Market presence since

2013 testifying to its

safety and efficacy.

0 1 2 3

-50

0

50

100

150CLS 01

CLS 04

CLS 07

OPU 01

Inhibitor (ug/ml)

% In

hib

itio

n

CLS 02

-1 0 1 2 30

50

100

150

Inhibitor (ug/ml)

% In

hib

itio

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We Got International Recognition!

(Earlier known as Omaria-P)

5 international publications pertaining to

it’s antimalarial efficacy!

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Punica granatum - an ideal profile as COVID-19 therapeutic agent

SARS-CoV-2 is an enveloped virus

Envelop protein

Membrane protein

Spike protein

Nucleocapsid protein

Enclosing RNA

Lipid membrane

Anti-viral [5]

o Action on enveloped viruses well documented

o Mechanism of action covers Viral entry, Viral integrity

and Viral replication depending on the virus

o Antiviral action documented on RNA as well as DNA

viruses

o Reduces glycosylation of ACE receptors thereby

supplementing its direct antiviral properties

Anti-inflammatory [5]

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

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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

01 Viral Entry

Influenza-A H3N3 Punicalagin

Hepatitis-C Delphinidin

HIV HIV 1 Flavonoid-ECGC

Herpes Simplex Virus Type I & II Flavonoid-ECGC

Hepatitis-B Flavonoid-ECGC

Zika Flavonoid-ECGC

02 Viral Integrity

Influenza-A H1N1 / H3N3 Phenolic acid-Gallic Acid

Herpes Simplex Virus Type I & II Procyanidin B2

Dengue Virus DEN 2 Flavonoid-ECGC

03 Viral ReplicationInfluenza-A H9N2 Flavonoid-ECGC

Hepatitis-B Phenolic acid-Caffeic Acid

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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,

consisting of phenolic compounds that readily donate

electrons to free radicals, converting them to relatively

stable compounds

o Beneficial effect of PgE for the treatment of malarial

disease is attributed to the anti-parasitic activity and the

inhibition of the pro-inflammatory mechanisms involved in

the onset of cerebral malaria

o Severe falciparum malaria is an inflammatory cytokine driven disease.

Malaria haemozoin and TNF promote MMP-9 which accentuates the

host inflammatory response. PgE inhibit secretion of MMP-9 as well as

NF-kB pathway driven transcription factors to limit progression to

severe form of the disease.

o The anti-inflammatory components of PgE, i.e., punicalagin, punicalin,

strictinin A and granatin B significantly inhibit the expression of pro-

inflammatory proteins

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

the treatment of Covid-19.

Opunika® (Punica granatum) -Repurposed for COVID-19

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Opunika® vs Hydroxychloroquine for Covid-19

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

Inhibition of Viral fusion at the site of host cell

membraneSupported by invitro studies

Disruption to virus entry through structural damage

demonstrated against RNA and DNA viruses.

Suppression of viral entry through altered

glycosylation of ACE-2Supported by invitro studies

PgE have been proven in invitro and invivo studies

regarding reduction of glycosylation of ACE

receptors hence impairing viral entry.

Inhibition of intracellular Viral replication

through Endosomal pH regulation Supported by invitro studies

Viral replication inhibition in Influenza-A reassortant

strains proved invitro studies.

Disruption of virion assembly and release Not well documented Well documented against enveloped viruses.

Immunomodulation of cytokine stormProven in immunomodulatory use

such as arthritis

Potent immunomodulation through NF-kB pathway

resulting in taming of the Cytokine cascade proven

in P.falciparum malaria.

Tolerability profileGood safety profile and well

toleratedGood safety profile and well tolerated.

Potential profile of PgE in Opunika® (compared with Hydroxychloroquine [2][5] ) show promise for ready

deployment

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Opunika® Extracts Have Been Standardized through Validation

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.

Analytical methods developed inhouse and validated at third party labs through LC-MS-MS (Data on file)

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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

The way forward against Covid-19

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 various parameters.

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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

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

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

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Thank You

Shubhendu Kumar Dash

Director (Founder), CONSYTEL

info@consytel.com

+91-7207205096

We desire a “Covid-19 free” India naturally