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Biosilver + CEP ->Covid: Biosilver nanoparticles with payload of CEP

by Subhramani Naidu

Biosilver nanoparticles with payload of Cepharanthine causes disruption of viral cell membrane
Mumbai, MH India COVID-19 Precision Medicine Equity Raise WarOnCOVID challenge

All Team Company Mission Innovation Details Investor Info Due Diligence Docs Supporters Comments Updates

About our project

The problem we solve: Currently there is no effective treatment for COvid-19. Additionally health condition like cancer, tuberclosis, respiratiory diseases can be effectively treated using this novel combination.

About our solution: The goal of this product is to substantiate potential antimicrobial bio-silverformulation to deliver plant-derived antiviral alkaloid (Cepharanthine (CEP)) by inhalation, to minimise the aggravation of respiratory system infections caused by SARS-CoV-2. This product aims at the major contribution that nanotechnology solutions can bring to mitigate the acute and chronic effects of COVID-19 pandemic from the protection and medication point of view by potentially blocking viral replication of SARS-CoV-2. This product containing silver nanoparticles with the size in the range of less than 100 nm and coated with polyethylene glycol (PEG) can be deliver in the form of dry powder inhaler via oral inhalation in the form of single use capsules or multi-dose inhalers such as sunhaler or Advair diskus. We proclaim that for significant antiviral effectiveness the size of silver nanoparticlesneeds to be less than 100nm, preferably in the range 15nm-70nm size.

Progress to date:

BioSilver,CEP and PEG order has been placed with vendors and to be combined at Adhya BioScience

Provisional Patent has been filed and now IP protection of the formulation is protected for 12 months

About Our Team

Creator: Subhramani Naidu

Location: Meath

Bio: A business researcher with top tier investment banking having expertise across sectors and geographies.

Title: Promoter

About Team Members

Dr Shrinidh Joshi
Scientific Advisor, PHD
Biography: An accomplished US based scientist, currently Technical Project leader with leading MNC. Also startup ACe2Stem focusing on Angiotensin and stem cell regeneration.
Title: Scientific Advisor
Advanced Degree(s): PHD

Dr. Varaprasad . Bobbarala
Chief Scientist & Director. Adhya Biosciences Pvt. Ltd, PhD
Biography: Dr Varaparasad is the an eminient scientist and Director of Adhya bioscience. Please follow the link to know more about his research papers: https://scholar.google.co.in/citations?user=C4cFOlIAAAAJ&hl=en
Title: Chief Scientist & Director. Adhya Biosciences Pvt. Ltd
Advanced Degree(s): PhD
LinkedIn: https://www.linkedin.com/in/adhyabio/

About Our Company

QuickGun LifeScience

Location: 402, Mehivish Tower, Patel Complex, Mira
Mumbai, MH 401107
IN

Founded: 2020

Product Stage: Prototype/MVP

Employees: 1-2

Challenge Mission

COVID Problem We Address

Effective treatment for Covid is producted by our product. Both biosilver and Cepharanthine are known ingredients with well documented studies on the efficacy against virus in vitro as well as having a good safety profile. Our product can be either a standalone medicine or can be included in the prescription list for Covid patients along with regular drugs to reduce viral load. 

Our COVID Solution

Our product is precisely engineered to target corona virus membrane. Silver binds to gylcoprotien in virus envelope and CEP also interacts with gylcoprotiens and stops virus from replicating. This double attack strategy of focussing on a common point of gylcoprotiens by both the ingredient of our product may result in better disruption of the viral membrane as compared to current market products. Additionally CEP is also anti-inflamatory which will reduce the cytokine releases.

Innovation Details

Intellectual Property Summary

Applicant                         : SUBRAMANI GOPAL NAIDU               

Application Number        : 202021024480

Date of filing                   : June 11, 2020

Title of invention             : BIO-SILVER NANOPARTICLE FORMULATION FOR TREATMENT OF VARIOUS DISEASES INCLUDING CORONA VIRUS DISEASE (COVID-19)

Type of Application         : Provisional

Clinical Information

QuickGun LifeScience

 

BioSilver Nanoparticles Loaded with CEP

 

Introduction to Cepharantine (CEP):

Reference : 1

 

Cepharanthine (CEP) is a naturally occurring alkaloid derived from Stephania cepharantha and

have unique anti-inflammatory, antioxidative, immunomodulating, antiparasitic, and antiviral

properties. Its therapeutic potential as an antiviral agent has never been more important in

combating COVID-19 caused by severe acute respiratory syndrome coronavirus type 2 (SARSCoV-2) virus and resulting so far in over four million cases since its onset.

 

 

Mechanism of action of CEP:

Reference : 2

 

Cepharanthine suppresses nuclear factor-kappa B (NF-κB) activation, lipid peroxidation, nitric

oxide (NO) production, cytokine production, and expression of cyclooxygenase; all of which are

crucial to viral replication and inflammatory response. Against SARS-CoV-2 and homologous

viruses, CEP predominantly inhibits viral entry and replication at low doses; and was recently

identified as the most potent coronavirus inhibitor among 2,406 clinically approved drug

repurposing candidates in a preclinical model. This analyzes and consolidates available evidence

establishing CEP’s potential therapeutic importance as a drug of choice in managing COVID-19

cases. So far, encouraging preclinical evidence about CEP’s safety profile, wide availability, and

unique antiviral properties especially against specific beta-coronaviruses supports its use as a drug

of choice in the treatment of human coronavirus diseases. However, further in vivo testing and

clinical trials are urgently required to provide additional data supporting the development of CEP

into antiviral medications, spurred by its superior antiviral and antiinflammatory activities in

preclinical settings relative to established antiviral agents. The ability of CEP to disable the

attachment and entry of SARS-CoV-2 into target cells demonstrates its great therapeutic potential

as a drug to combat COVID-19. Also, its low EC50 and CC50 achievable with oral dosing, and

synergistic properties when combined with other antiviral medications (such as nelfinavir 9 and

mefloquine), further supports its excellent pharmacokinetic profile and establishes its importance

in the fight against COVID-19.

 

 

CEP binding to gycloprotien at viral entry and postentry viral replication.

Reference – 3

 

CEP binds to gylcoprotien and prevents it from engaging with viral receptor. Cepharanthine

prevents the virus from attaching to and entering cells. The CEP molecule binds to the spike

glycoprotein of the virus and prevents it from engaging with the viral receptor. This is the

angiotensin-converting enzyme 2 (ACE2).

CEP is useful against Corona Screening drug studies on pangolin SARS-CoV-2, which is the human-related Coronavirus, demonstrated that three drugs (cepharanthine, selamectin and mefloquine hydrochloride) were effective in inhibiting viral replication, with cepharanthine potently inhibiting coronavirus infection

 

 

Silver Binding to gylcoprotien

Reference : 4

 

Silver binds to viral gylcoprotien and same stands true in case of similar virus like Corona. Recent

studies have identified the broad-spectrum antiviral properties of silver nanoparticles (AgNPs)

against respiratory pathogens, such as adenovirus, parainfluenza, and influenza. AgNPs achieve

this by attaching to viral glycoproteins, blocking entry into the host cell. Silver binds to viral

gylcoprotien is concluded in the study. The regular spatial arrangement of the attached

nanoparticles, the center-to-center distance between nanoparticles, and the fact that the exposed

sulfur-bearing residues of the glycoprotein knobs. would be attractive sites for nanoparticle

interaction suggest that silver nanoparticles interact with the HIV-1 virus via preferential binding

to the gp120 glycoprotein knobs. Due to this interaction, silver nanoparticles inhibit the virus from

binding to host cells, as demonstrated in vitro.

 

 

 

Nanoparticles in treatment:

 

Researchers have been investigating the potential of using nanoparticles to treat bacterial and viral

infections for years now. The idea of using nanoparticles, is that the SARS-CoV-2, which is the

virus behind COVID-19 consists of a structure of a similar scale asnanoparticles. Gold

nanoparticles, for example, are made to attach to viruses such as Ebola or influenza and by heating

the particles with certain infrared wavelengths, the nanoparticles can then destroy the structure of

the virus. Nanoparticles can be used to deliver drugs as well. Silver on the other hand, has been

the most extensively studied metal for purpose of fighting infections and preventing food spoilage,

and notwithstanding the decline of its use as a consequence of the development of antibiotics,

prophylaxis against gonococcal ophthalmia neonatorum with silver ions was considered the

standard of care in many countries until the end of the 20th century.Antibacterial, antifungal and

antiviral properties of silver ions and silver compounds have been extensively studied. Silver has

also been found to be non-toxic to humans at very small concentrations. The microorganisms are

unlikely to develop resistance against silver as compared to antibiotics as silver attacks a broad

range of targets in the microbes.The antimicrobialproperties of silver nanoparticles are well

established and is medically FDA approved in field of woundcare. Bio-silver nanoparticles are

chemically inert and does not contain any side effects associated with the chemically synthesized

silver nanoparticles and are non-toxic. The goal of this product is to substantiate potential

antimicrobial bio-silverformulation to deliver plant-derived antiviral alkaloid (Cepharanthine

(CEP)) by inhalation, to minimise the aggravation of respiratory system infections caused by

SARS-CoV-2. This product aims at the major contribution that nanotechnology solutions can bring

to mitigate the acute and chronic effects of COVID-19 pandemic from the protection and

medication point of view by potentially blocking viral replication of SARS-CoV-2. This product

containing silver nanoparticles with the size in the range of less than 100 nm and coated with

polyethylene glycol (PEG) can be deliver in the form of dry powder inhaler via oral inhalation in

the form of single use capsules or multidose inhalers such as sunhaler or Advair diskus. We

proclaim that for significant antiviral effectiveness the size of silver nanoparticlesneeds to be less

than 100nm, preferably in the range 30nm-70nm size. The PEG coating on the silver nanoparticles

will ensure there is minimal clearance of nanoparticles in the spleen and liver by macrophages and

Kupffer cells.

 

 

 

Animal Studies:

Reference : 5

 

Biologically synthesized AgNPs with an average size of 60 nm with concentrations of 15 and 20 mg/kg of AgNPs-loaded vaccine injected into the mice and dogs. The in vivo toxicity also elucidated the safety of AgNPs and AgNPs-loaded vaccine in mice and dogs, respectively. Safety test for veterinary use was carried out on two healthy female dogs. After administration of AgNPs-loaded rabies vaccines, the animals were daily monitored for 14 days. The animals did not show signs of either disease or local and systemic reactions and no fever or death was observed due to the vaccine during monitoring. The study shows that AgNPs can be used as adjuvant in rabies veterinary vaccine. AgNPs interact with the virion surface as well with the virion core Peste des petits ruminants virus and it shows that there is no significant effect on the virucidal effect, instead it exerts a blocking effect on viral entry into the target cells. The antiviral activity of tannic acid modified various sizes of AgNPs was studied. The study concluded that it required direct interaction and blocked virus attachment, penetration, and further spread.

 

bioSilver nanoparticles in Ayurveda:

Reference : 6

 

Silver has been processed using herbal extracts as reducing agent to form bhasma in Ayurveda. There is a history of consumption of this preparation in India. Currently there are several type of biometallic nanoparticles being used in Ayurvedic medicines in India approved by regulator. There has no report of adverse cases caused by consumption of bhasmas. Scientific analysis on Rajat bhasma showed that Silver nanoparticles was spherical in the range of 5–50 nm and uniformly distributed without significant agglomeration. This proves silver bhasma used in Ayurveda are nanoparticles and widely used since ancient times.

 

 

 

 

 

 

 

 

 

 

References:

1)

? MedInsight Research Institute, Rehovot, 7670204, Israel

? Institute for Personalized and Translational Medicine, Ariel University, Ariel 40700, Israel

2)

Rogosnitzky, Moshe & Okediji, Paul & Koman, Igor. (2020). Cepharanthine: A review of the antiviral potential of a Japanese-approved alopecia drug in COVID-19. 10.31219/osf.io/5e9gk.

3)

Elechiguerra, J.L., Burt, J.L., Morones, J.R. et al. Interaction of silver nanoparticles with HIV-1. J Nanobiotechnol 3, 6 (2005).

? Claudia Cava 1,* , Gloria Bertoli 1,* and Isabella Castiglioni 2 1 Institute of Molecular

Bioimaging and Physiology, National Research Council (IBFM-CNR), Via F.Cervi 93,

20090 Segrate-Milan, Milan, 2017, Italy

? Department of Physics “Giuseppe Occhialini”, University of Milan-Bicocca Piazza

dell’Ateneo Nuovo, 1 – 2012 6, Milan, Italy

News Medical LifeSciences  

4)

Dorothea Morris, Maria Ansar, Janice Speshock, Teodora Ivanciuc, Yue Qu, Antonella Casola, Roberto Garofalo

Sealy Center for Environmental Health Medicine Pediatrics

5)

Ding-Ping Bai 1,†, Xin-Yu Lin 1,†, Yi-Fan Huang 1 and Xi-Feng Zhang 2,*

Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health,

Fujian Agriculture and Forestry University, Fuzhou 350002, China; bdpnx@163.com (D.-P.B.);

linazong1991@foxmail.com (X.-Y.L.); yfanhuang@163.com (Y.-F.H.)

College of Biological and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan 430023,

6)

Ayu Journal - PHARMACOLOGICAL STUDY. Year : 2016 | Volume : 37 | Issue : 1 | Page : 71-75. Physicochemical characterization and antibacterial activity of Rajata Bhasma

1 Department of Microbiology, MGM Medical College and Hospital, Navi Mumbai, Maharashtra, India

2 Department of Medical Biotechnology, MGMIUDBS, MGM Institute of Health Sciences, Navi Mumbai, Maharashtra, India

3 Department of Biotechnology, Central Research Laboratory, MGM Institute of Health Sciences, Navi Mumbai, Maharashtra, India

 

 

 

 

 

Links:

 https://www.news-medical.net/news/20200419/Research-suggests-Nelfinavir-and-Cepharanthine-as-potential-anti-SARS-CoV-2-agents.aspx

https://doi.org/10.1186/1477-3155-3-6

https://pubmed.ncbi.nlm.nih.gov/32268515/

https://researchexperts.utmb.edu/en/publications/antiviral-and-immunomodulatory-activity-of-silver-nanoparticles-i

https://jnanobiotechnology.biomedcentral.com/articles/10.1186/1477-3155-3-6

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274759/

http://www.ayujournal.org/article.asp?issn=0974-8520;year=2016;volume=37;issue=1;spage=71;epage=75;aulast=Sharma

 

Regulatory Status

We plan to formulate the product in India and do clinical research. On success of clinical trial, the product will be outsourced for manufacturing, while we retain the IP and Brand. We anticipate fast track approval in India as both ingredients can be considered nanopharmaceutical and regulation are supportive of usage. Also due to Covid crisis, govt is fastracking Covid related medicines. Iam planning to fund the formulation and invitro trials primarily but with strategic partner we can have a global vision

How we will use the funds raised

Initially the fund will be used to conduct invitro trials, animal trials and human trial. The amount collected would be used in finetune the product, conduct additonal research & clinical trials in European countries and US for FDA approval. Further funds will be to market the product globally.

Thank You

This invention is valuable in treating Covid further strengthen the application of ancient observation with bleeding edge technologies.

Also Investor will have access to our ready biotech product which has application in cosmetics, electric car, fuel cell and others

This project is related to a social justice enterprise, we mean by what we say, Social Justice Enterprise, Uncoventional but effective. 

Health is Wealth and we protect it

Investor Info

Market Size

Covid Therapy is worldwide multibillion dollar opportunity

TB Drugs Market Size Worth $1.38 Billion By 2025 | CAGR: 5.2% The global tuberculosis drugs/therapeutics (TB) market size is expected to reach USD 1.38 billion by 2025, according to a new report by Grand View Research, Inc., registering a CAGR of 5.2% during the forecast period

https://www.grandviewresearch.com/press-release/global-tuberculosis-tb-drugs-therapeutics-market#:~:text=The%20global%20tuberculosis%20drugs%2Ftherapeutics,5.2%25%20during%20the%20forecast%20period.

Further market exists for Cancer, Hairloss etc.

Both ingredients of the drug combination has well known and documented efficiacy against Covid aand Tuberclosis.

This nano delivery system of Biosilver containing payload of CEP is a silver bullet for multiple health condition

Projected 3 Year Growth

We anticipate 10% market penetration of TB which can be estimated upto $30 million in revenue.

Covid Therapy on successful trials can up the value of the firm by multiple times.

Revenue Model

We plan to retain brand and Intellectual property outsourcing the manufacturing process to suitable firm. We are in the process of possible ways of commercialisation through a Biotech Innovation specialist Ploemen LifeSicence consultancy who has recommeded developing the product. Further Adhya BioScience will be conduct synthesis formulation and oversee the product development.

Competitors

There are 70 coompanies which have trials in Covid. Our product is based on validated and documented research on its effectiveness iin Covid. It can get fast track approval and even incase Corona anitvirus is launched, it still has application in Tuberclosis, Cancer, and other health condition. We think its a silver bullet to several health condition and hence we will have a steady market.

Traction

Partners:

Adhya Bioscience to formulate and oversee to enhance product properties.

www.adhyabio.com

Pranada Biopharma to do the marketing and clinical trials of the product.

www.pranadabiopharma.com

Biotech consultancy from Nederland, USA and France have validated the product as innovative strategy.

Due Diligence Docs

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