This document discusses repurposing polyphenolic extracts from Punica granatum (Opunika®) for treating COVID-19. It notes that Punica granatum has proven anti-malarial and anti-inflammatory properties. It suggests that Punica granatum's anti-viral effects against enveloped viruses, ability to reduce ACE receptor glycosylation, and anti-inflammatory mechanisms through NF-kB pathway inhibition make it a promising therapeutic agent against SARS-CoV-2. It proposes in vitro testing of Punica granatum extracts against SARS-CoV-2 followed by a clinical trial in COVID-19 patients to evaluate its potential as a COVID-19 treatment.

1. #COVID19 #Coronavirus
Polyphenolic Extracts from Opunika® (Punica granatum)
– Repurposed for COVID19

2. #COVID19 #Coronavirus
Opunika®: Proven Antimalarial, now 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 %
1
Mode of Action[1]
Ellagic Acid and Ellagitannins in Punica granatum are
the active moieties contributing to anti plasmodial
action along with D.sylvatica
2
Coverage[1]
Plasmodium vivax and Plasmodium falciparum induced
malaria
5
Tolerability 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
4
Toxicity 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
150
CLS 01
CLS 04
CLS 07
OPU 01
Inhibitor (ug/ml)
%Inhibition
CLS 02
-1 0 1 2 3
0
50
100
150
Inhibitor (ug/ml)
%Inhibition

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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

6. #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
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 Replication
Influenza-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

8. #COVID19 #Coronavirus
Opunika® vs Hydroxychloroquine for Covid-19
Postulated mechanism / Profile Hydroxychloroquine P.granatum Extracts (PgE)
Inhibition of Viral fusion at the site of host cell
membrane
Supported 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-2
Supported 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 storm
Proven 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 profile
Good safety profile and well
tolerated
Good 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 ventilator support.

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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

12. R&D: Atal Innovation Centre, CCMB Annexe-2,Habsiguda,Hyderabad
Works: Plot No.66-A, Phase-IV, IDA Jeedimetla, Hyderabad
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#COVID19 #Coronavirus
Thank You
Shubhendu Kumar Dash
Director (Founder), CONSYTEL
consytelbiz@gmail.com
+91-9030739849
We desire a “Covid-19 free”
India naturally