DESC:FIELD
The present disclosure relates to the field of homeopathic formulations, particularly to nosodes for the prevention, alleviation of symptoms and treatment of viral infections.
DEFINITIONS
As used in the present disclosure, the following terms are generally intended to have the meaning as set forth below, except to the extent that the context in which they are used indicate otherwise.
Viral Infection : The term viral infection used in this disclosure generally relates to any viral infection and particularly to a SARS virus or Corona virus or a MERS virus.
Centesimal Potency: The term “centesimal potency” refers to the principle that the first potency must contain one-hundredth part of the original drug and each succeeding potency must contain one-hundredth part of the preceding one. This scale is designated by suffixing the letter 'C' or 'CH' to the number indicating the potency i.e. the first potency is 1C or 1CH, followed by 2C or 2CH and so on.
Nosode:The term “Nosode” refers to a very dilute and potentized homeopathic formulation obtained from pathological tissue sample taken from the blood, feces, mucus, pus or tissue of an affected body part or organism such as bacteria, virus or parasites, and which is rendered safe during the homeopathic manufacturing process.
Potency: The term “potency” refers to the power that is derived by the grades of medicinal power developed by the process of potentization. Potency is a result of a series of successive dilutions and potentization, according to scale and friction through succussion or trituration.
Potentization: The term “potentization” refers to the process of making a remedy more potent by serial dilution and forceful stroking. Potentization is the process for increasing the therapeutic potency by the reduction, according to scale, of crude, inert or poisonous medical substances to a state of physical solubility, physiological assimilability and therapeutic activity and harmlessness, for use as homeopathic remedies.
Succussion: The term “succussion” refers to the vigorous shaking (powerful stroking) of a diluted homeopathic preparation in order to activate the medicinal substance. Succussion is the process of potentization, by which preparation of medicine takes place by the use of a liquid vehicle like alcohol or water, by shaking in a definite method.
BACKGROUND
The background information herein below relates to the present disclosure but is not necessarily prior art.
Virus infections are difficult to treat. There have been a series of virus infections that have turned to epidemics or pandemics. One of the earliest known viral infections was the Influenza infection around 1918. Recently, there has been the COVID-19 outbreak. The COVID-19 outbreak first came to light in December, 2019 when China informed the World Health Organization of a cluster of cases of pneumonia of an unknown cause in Wuhan City in its Hubei province. Since then the COVID-19 outbreak has spread across several continents and has been declared a pandemic by the World Health Organization. The virus has been named SARS-CoV-2 and the disease is now called COVID-19.
People infected with COVID-19 have reported a wide range of symptoms ranging from mild symptoms to severe illness. The initial symptoms of the diseases are fever, tiredness, dry cough, muscle pain and loss of sense of taste and/or smell. As the disease progresses the symptoms worsen and further include shortness of breath or difficulty in breathing, persistent pain or pressure in the chest and bluish lips or face. However, currently there is no medicine for the effective alleviation of symptoms and treatment of COVID-19.
Therefore, there is felt an urgent need to provide a medicine for the treatment of virus infections.
OBJECTS
Some of the objects of the present disclosure, which at least one embodiment herein satisfies, are as follows:
An object of the present disclosure is to provide a medicine for the prevention, alleviation of symptoms and treatment of viral infections.
Another object of the present disclosure is to provide a homeopathic medication for the prevention, alleviation of symptoms and treatment of viral infections.
A further object is to provide a homeopathic medication for the treatment of viral infections which has no side effect, is safe to manufacture and is also relatively inexpensive.
Yet another object of the present disclosure is to provide a method of preparing the nosode composition for prevention, alleviation of symptoms and treatment of viral infection, which is simple and cost-effective.
Other objects and advantages of the present disclosure will be more apparent from the following description, which is not intended to limit the scope of the present disclosure.
BRIEF DESCRIPTION
The present disclosure will now be described with the help of the accompanying drawing:
Figure 1 illustrates a scatter chart comparing two sets of CD4 data (day 30-60 and day 80-105) in volunteers administered with the composition of the present disclosure.
DETAILED DESCRIPTION
Embodiments, of the present disclosure, will now be described in detail.
Embodiments are provided so as to thoroughly and fully convey the scope of the present disclosure to the person skilled in the art. Numerous details are set forth, relating to specific components, and methods, to provide a complete understanding of embodiments of the present disclosure. It will be apparent to the person skilled in the art that the details provided in the embodiments should not be construed to limit the scope of the present disclosure. In some embodiments, well-known processes, well-known apparatus structures, and well-known techniques are not described in detail.
The terminology used, in the present disclosure, is only for the purpose of explaining a particular embodiment and such terminology shall not be considered to limit the scope of the present disclosure. As used in the present disclosure, the forms "a,” "an," and "the" may be intended to include the plural forms as well, unless the context clearly suggests otherwise. The terms "comprises," "comprising," “including,” and “having,” are open ended transitional phrases and therefore specify the presence of stated features, integers, steps, operations, elements, modules, units and/or components, but do not forbid the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. The particular order of steps disclosed in the method and process of the present disclosure is not to be construed as necessarily requiring their performance as described or illustrated. It is also to be understood that additional or alternative steps may be employed.
As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed elements.
Viral infections are generally infectious and may also be contagious. For eg. Corona virus disease COVID-19 is both, an infectious and a contagious disease caused by a corona virus, SARS-CoV-2. It is believed that the virus that causes COVID-19 is mainly transmitted through droplets generated when an infected person coughs, sneezes, or exhales. Other means of transmission have also been suggested, for e.g., fecal transmission. The signs and symptoms of COVID-19 appear 2 to 14 days after exposure.
Currently, as on November 2020, there is no prevention or cure for COVID-19 and the best way to remain uninfected is to prevent exposure to the disease. Therefore, there is felt a need for a medicine for the alleviation of symptoms and treatment of viral infections, particularly COVID-19.
In one embodiment of the present disclosure there is envisaged a homeopathic medicine in the form of nosodes for the prevention, alleviation of symptoms and treatment of viral infections.
In accordance with an aspect of the present disclosure there is provided a homeopathic medicine in the form of a nosode for the prevention, alleviation of symptoms and treatment of viral infections. The nosode comprises at least one component selected from:
a. live virus;
b. viralspike glycoprotein;
c. inactivated virus;
d. viral envelope protein;
e. viral nucleocapsid protein; and
f. virus irradiated infected cell lysate.
In accordance with an embodiment of the present disclosure, any one of the components can be used alone to form a nosode composition or can be used as a combination of two or more components or in a combination of all six components to form the nosode composition for prevention, alleviation of symptoms and treatment of viral infections.
In accordance with an embodiment of the present disclosure the nosode is formulated in at least one dosage form selected from the group consisting of pills, liquid drops, oral tinctures, spray and injectable.
In accordance with an embodiment of the present disclosure, the nosode is intended for oral administration. Other forms of administration can also be envisaged such as pills in the form of lactose globules.
The viral infection is at least one of Coronavirus disease 2019 (Covid-19), Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS).
The biological material comprises a virus and/or a viral component. The virus and/or the viral component for the preparation of nosode is obtained from at least one of SARS CoV-2, SARS-CoV and MERS-CoV.
In accordance with an embodiment of the present disclosure, the live virus is obtained either from clinical samples of an infected person who is negative for other common cross-infections. This is further confirmed by META-genic testing or a virus culture.
In accordance with an embodiment of the present disclosure, the inactivated virus is inactivated using heat, gamma irradiation and the like.
In an exemplary embodiment of the present disclosure, there is provided a nosode composition for the prevention, alleviation of symptoms and treatment of Covid -19. The biological material used for the preparation of nosodes can be obtained from viral culture of SARS CoV-2.
In another embodiment the nosode is prepared from live virus of SARS CoV-2, viral spike glycoprotein of SARS CoV-2, inactivated SARS CoV-2 virus, viral envelope protein of SARS CoV-2, and viral nucleocapsid protein of SARS CoV-2 nucleocapsid N protein.
In accordance with an embodiment of the present disclosure, there is provided a nosode composition for the prevention, alleviation of symptoms and treatment of MERS. The biological material used for the preparation of nosodes is obtained from viral culture of MERS-CoV.
In accordance with an exemplary embodiment of the present disclosure, the biological material used for the preparation of nosodes is obtained from viral culture of virus irradiated infected cell lysate of MERS CoV.
In accordance with an embodiment of the present disclosure, the potency of the nosode composition can be in the range of 1c to 10000 c. In an exemplary embodiment of the present disclosure, the effective potencies of the nosode are 7c, 15c, 30c, 50c, 100c, 200c and 1000c.
In accordance with another aspect of the present disclosure, there is provided a method for preparation of a nosode composition for the prevention, alleviation of symptoms and treatment of viral infections. For preparing the nosode composition, the live virus is obtained either from clinical samples of infected person or viral culture. In an exemplary embodiment of the present disclosure, the live virus is obtained from an oropharyngeal swab (clinical sample) of a virus infected patient. The viral infection is at least one of coronavirus disease 2019 (Covid-19), Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The clinical sample is collected in a Viral Transport Medium (VTM). Subsequently, at least one biological material is obtained from the clinical sample. The biological material is processed to obtain an Original Stock Nosode (OSN). The biological material comprises at least one component selected from:
a. live virus;
b. viralspike glycoprotein;
c. inactivated virus;
d. viral envelope protein;
e. viral nucleocapsid protein; and
f. virus irradiated infected cell lysate.
The virus and/or the viral component for the preparation of nosode is obtained from at least one of SARS CoV-2, SARS-CoV and MERS-CoV.
In accordance with an embodiment of the present disclosure, the inactivated virus is inactivated using heat, gamma irradiation and the like.
In accordance with an exemplary embodiment of the present disclosure, the biological material used for the preparation of nosode composition for the prevention, alleviation of symptoms and treatment of Covid-19, is obtained from the viral culture of inactivated SARS CoV-2 virus. In one embodiment, live SARS CoV-2 virus is heated at a temperature in the range of 60°C to 70°C for a time period of 20 minutes to 40 minutes to obtain the heat inactivated SARS CoV-2 virus.
In accordance with another exemplary embodiment of the present disclosure, the biological material used for the preparation of nosode composition for the prevention, alleviation of symptoms and treatment of Covid-19, is obtained from SARS CoV-2 spike glycoprotein. The spike glycoprotein is obtained from severe acute respiratory syndrome-related Coronavirus 2 (SARS-CoV-2) and Wuhan-Hu-1 (GenPept: QHD43416), and wherein the glycoprotein contains 223 residues of the SARS-CoV-2 spike glycoprotein Receptor Binding Domain (RBD) and a C-terminal hexahistidine tag. In accordance with an embodiment of the present disclosure, there is provided a nosode composition for the prevention, alleviation of symptoms and treatment of MERS. The biological material used for the preparation of nosodes is obtained from viral culture of MERS CoV.
In accordance with an exemplary embodiment of the present disclosure, the biological material used for the preparation of nosodes is obtained from viral culture of virus irradiated infected cell lysate of MERS CoV.
The biological material thus obtained is mixed with sterile water to obtain the Original Stock Nosode (OSN). The biological material obtained for making the nosodes are obtained from the USA.
The OSN is further subjected to dilution in a physiologically acceptable medium to obtain a diluted mixture. In accordance with an embodiment of the present disclosure, the physiologically acceptable medium is water, typically Water for Injection.
In accordance with another exemplary embodiment of the present disclosure, the medium used for the first dilution up to a predetermined potency is water.
The physiologically acceptable medium used for preparation of the nosodes in accordance with the present disclosure yield nosode composition having potencies in the range of 1c to 5c since the viral components remain neutral in this medium.
The diluted mixture is then subjected to serial dilution with at least one vehicle to obtain the nosode composition. The vehicle can be at least one of alcohol and water. The serial dilution is carried out by maintaining a dilution ratio in the range of 1:99 to 10:90 between the diluted mixture and the vehicle.
After every step of serial dilution, the mixture is subjected to potentization by exerting forceful strokes (stroking) to obtain the nosode composition having optimally effective potencies of 7c, 15c, 30c, 50c, 100c, 200c and 1000c, although other potencies are also effective.
It is observed that for potencies in the range of 1c to 5c, the protein present in the viral component denatures in alcohol and therefore the efficacy of the nosode is reduced. Therefore, alcohol can be used as the medium for serial dilution of nosodes having potency above 5c. In accordance with one embodiment a mixture of alcohol and water can be used for serial dilution.
The nosodes are prepared from each of the components individually up to 5c potency. Two or more of the nosodes, prepared individually, can be combined at 6c potency or higher in equal proportion for further potentization.
In accordance with an embodiment of the present disclosure, the nosodes having potency of 6c or above are made using a single or a combination of two or more nosodes made from the components stated above or made by combining individual six nosodes having predetermined potency in equal proportion.
Particularly, for administering to patients, the nosodes made from individual components or nosodes made by combining nosodes of two or more components are administered to the patient typically at 30c potency. 30c potencies of each individual or combined nosodes are subjected to testing for any contamination with any other infections.
The nosodes having potency of 5c and above can also be subjected to testing for safety and in case of detection of any cross-contamination, the nosodes are discarded. In homeopathy, lower potencies contain higher amount of starting material, and hence have comparatively higher toxicity. Therefore, a 15c potency has higher comparative toxicity, it is selected for acute toxicity evaluation. The nosodes of potency 6c, 30c and 100c are also subjected to testing using the RT-PCR method to confirm the absence of biological (RNA) material, thereby confirming that the nosode is safe and non-infectious. Further, the nosodes of 30c potency are also subjected to testing using other conventionally known methods such as Viro Cells to ensure that they are not capable of causing infection.
The nosodes prepared in accordance with the present disclosure exhibit an anti-viral activity particularly anti SARS-CoV2 activity.
The foregoing description of the embodiments has been provided for purposes of illustration and is not intended to limit the scope of the present disclosure. Individual components of a particular embodiment are generally not limited to that particular embodiment, but, are interchangeable. Such variations are not to be regarded as a departure from the present disclosure, and all such modifications are considered to be within the scope of the present disclosure.
The present disclosure is further described in the light of the following trials which are set forth for illustration purpose only and not to be construed for limiting the scope of the disclosure.
TRIAL DETAILS
Trial 1: Preparation of the nosode composition in accordance with the present disclosure.
For preparing the nosode composition, a clinical sample was obtained from oropharyngeal swab of a SARS CoV-2 virus infected patient who had recently returned from travel to the affected region of China and developed the clinical disease Covid -19. The swab sample was collected in a Viral Transport Medium (VTM). The sample containing SARS CoV-2 live virus was mixed with sterile water to obtain the Original Stock Nosode (OSN) of 1c potency. The OSN was further subjected to dilution in Water for Injection to obtain a diluted mixture
The diluted mixture was subjected to serial dilution and potentization by exerting forceful strokes (stroking) to obtain the nosode composition.
The serial dilution was carried out with a mixture of alcohol and water (as vehicle) and by maintaining a dilution ratio of 1:99 between the diluted mixture and the vehicle. Nosode compositions of potencies 7c, 15c, 30c, 100c, 200c and 1000c were prepared with such serial dilution.
The obtained nosode compositions for SARS COV-2, labelled as Coronavirus nosode CVN01, was then tested for safety, evaluation of immune response, and documentation of proving-symptoms in healthy volunteers.

Trial 2: An open-label, exploratory Phase I trial for safety, evaluation of immune response, and documentation of proving-symptoms of Coronavirus nosode in healthy volunteers.
A Phase I trial was conducted to evaluate the safety of the nosode of the present disclosure. For this study, Coronavirus nosode CVN01 was prepared, from the clinical sample of a patient having confirmed infection of SARS-Cov-2, in accordance with Trial 1, following various guidelines and protocols, at Haffkine Institute, Mumbai.
Study Design
This study was conducted at a single center in Mumbai, India. Phase I, open-label, and nonrandomized study was designed to examine the response of Coronavirus nosode CVN01 administered orally to healthy volunteers. The study was planned in three parts: Part 1 was a study to examine the safety in terms of clinical effects and blood parameters at base line and time points day 17, day 30, and day 60. Part 2 was to evaluate certain immune response, and part 3 was to document proving-symptoms experienced by the volunteers in response to the nosode.
Study Population
10 eligible volunteers in the age group of 18 years to 65 years who voluntarily signed informed consent forms, were enrolled in the trial. Among the 10 volunteers, four were males and six were females. The volunteers were found to be healthy after conducting normal routine laboratory parameters during screening with no major untreated diseases. The trial protocol was reviewed by the Scientific Advisory Board and approved by an Institutional Ethics committee. The trial was registered at the Clinical Trial Registry of India (CTRI) with Trial registration number: CTRI/2020/05/025496.
Interventions
A nosode prepared from the clinical sample coded as CVN01, of potency 30c (pill size 30) was administered as six doses, six pills twice daily for consecutive three days. Pre and post examinations, such as physical, vital signs, and laboratory investigations, were done at base line, on day 17 (14 days after the last dose), and a few investigations were repeated on day 30 and day 60.
Study End Points and Assessments
The primary end point of Part 1 was the determination of the safety of the CVN01 nosode. The primary endpoint of part 2 was the evaluation of the changes in immune response parameters, and part 3 was the recording of clinical symptoms experienced by the volunteers.
Similar trials were also conducted for different potencies, ranging from 1c to 1000c potencies, specifically potencies 7c, 15c, 30c, 100c, 200c and 1000c on different volunteers, depending on the severity of their condition and as prescribed by the homeopathic doctor. Similar results were observed for these potencies as well.
Safety Assessments
Safety assessments included the monitoring of volunteers for any unexpected symptoms, adverse events, serious adverse events, clinical and laboratory investigation results, blood pressure, physical examination findings, and general well-being.
Safety parameters measured included Complete Blood Count (CBC), C-Reactive Protein (CRP), Liver Function Test (LFT), and Serum ferritin level.
Immune response parameters measured included Interferon–gamma (IFN-y), Interleukin-6, Immunoglobulins- COVID-19 antibodies, and CD 4 panel.
The symptoms experienced by the volunteers during the study period were recorded. All symptoms were reported with location, sensation, duration, frequency, and concomitants, if any. A dull headache with the heaviness of head all over the head < 1-4 p.m. was found to be associated with sleepiness.
Every symptom described by the volunteers was graded as + (mild), ++ (moderate), +++ (severe) and ++++ (very severe). This method allowed qualification grading.
Volunteers who exhibited some symptoms prior to this study duration were eliminated, if the volunteer also exhibited the same or similar symptoms after consumption of study medication.
Similar symptoms experienced by more than one volunteers were considered as characteristic.
The Phase I trial results were reported in three parts. Table 1 below shows the P value (calculated probability) of various blood parameters that were measured along with liver function test.
Table 1
Sr. No Biological Parameters Day 0 Day 17 P value
1 White blood cell 7.234 7.529 0.2801
2 Red Blood cell 4.652 4.208 0.2834
3 Hemoglobin 12.97 12.97 1
4 Platelets 292.2 276.4 0.0724
5 Alkaline phosphatase 81.4 80.4 0.5897
6 Bilirubin Direct 0.172 0.231 0.0994
7 Bilirubin Total 0.377 0.573 0.0658
8 Total Protein 7.391 7.28 0.1193
9 Albumin 4.203 4.255 0.1920
10 AST/GOT 19.34 17.09 0.1679
11 ALT/GPT 20.99 16.74 0.2398
12 C-reactive Protein 1.4 1.61 0.4992
13 Ferritin 39.176 38.803 0.9009

Table 2 below shows measurement of Interleukin 6 (IL-6) at day 30 and day 60. It was observed that three volunteers showed elevated IL-6 on day 17, and all 10 volunteers showed elevated IL-6 on day 30. On repetition of IL-6 at day 60, the values of nine volunteers were found within the normal range.
Table 2
IL-6 (Interleukin-6) 0.00-7.00 pg/mL
Volunteer Day 0 Day 17 Day 30 Day 60
1. 1.5 3.67 10.4 3.34
2. 3.02 5.49 9.22 7.58
3. 2 6.42 44.6 5.93
4. 1.5 2.65 24.5 1.5
5. 2.5 8.23 41.8 1.59
6. 3.7 8.77 38.1 1.5
7. 1.5 3.91 23.4 4.14
8. 1.5 12 39.5 4.5
9. 1.5 4.9 35.7 4.5
10. 1.5 4.73 23.1 3.95
Mean 2.022 3.0677 29.032 5.829
P value 0.0009 0.000086 0.1193

A mild elevation of IL-6 in all the volunteers was linked to immune response, as there were no corresponding clinical signs and symptoms of inflammatory or pathological response. Also, no increase in C-Reactive Protein was observed despite an increase in IL-6, which was suggestive of non-inflammatory and non-pathological responses, thereby suggesting immune response. Volunteers did not show any clinically untoward symptoms because of the elevated IL-6 values.
All the volunteers reported a mild increase in IL-6 on day 17, and further rise on after 30 days, and subsequent decline corresponding with an increase in CD4 count on day 60, thereby suggesting activation of innate immunity in response to the nosode. IL-6 elevation peak at day 34 was observed and CD4 levels on the same day showed a strong correlation as compared to that on the day 60 visit.
Table 3 below shows measurement of CD4 at day 30, 60, 80 and 105 days. The nosode prepared from the SARS-CoV-2 virus showed an increase in CD4 cells suggesting improved immunity against COVID-19 infection.
Table 3
CD4 values at different time points
Volunteer Absolute CD4 (424.00-1509.00)/ul
Time point Day 30 Day 60 Day 80 Day 105
1. 630 567 650 719
2. 505 526 653 595
3. 1453 1520 1686 1817
4. 1037 1244 1057 926
5. 722 826 1004 936
6. 801 846 1255 1277
7. 628 693 643 586
8. 1010 1179 1349 909
9. 633 614 583 1010
10. 916 993 930 981

Figure 1 illustrates a scatter chart comparing two sets of CD4 data (day 30-60 and day 80-105) in volunteers administered with the composition of the present disclosure. The dots represent the series for absolute CD4 at day 60 and the squares represent the series for absolute CD4 at day 105. The position of each dot and square (on the X and Y-axis) indicates the value for an individual data point. This chart shows the relationship between paired (X, Y) quantitative data.
It is known to a person skilled in the art that increased levels of CD4 is effective against other viral infections also, for example HIV infections. Therefore, the ability of the nosode composition of the present disclosure to increase CD4 count is suggestive of its potential role against other viral infections, including HIV infections.
Further, it is well known that homeopathic nosodes have broad-spectrum effects. For example, a nosode Tuberculinum prepared from tissues containing Mycobacterium Tuberculosis bacteria has been used by homeopathic doctors against many conditions including bacterial, viral, and parasitic infections, as well as Rheumatoid arthritis, Migraine, psoriasis, and the like. Similarly, the nosode of the present disclosure, which is prepared from SARS-CoV-II virus has the potential to work as prophylactic and therapeutic against COVID-19, other forms of viral infections, like HIV, because of its immunomodulatory properties observed in Phase 1 study and clinical trials.
Antibodies:
Three volunteers out of ten developed SARS-CoV-2 antibodies on repeating the booster doses for three days from day 60.
Table 4 below shows severity of symptoms reported by the volunteers.
Table 4
Sr. no Location Symptom (Severity of symptoms in ascending order: +, ++, +++, ++++)
1. Head 1. Frontal headache for 4 days +++ (Volunteer no. 3)
2. Right side of head, neck (15 hrs.), Sudden severe throbbing pain, warm clothes, with overwhelmed feeling ++++ (Volunteer no. 6)
11. Heart 24. Palpitation on slight exertion + (Volunteer no.4)
12. Mind 25. Anxiety +++ (Volunteer no.6)
13. Generalities 26. Body pain full body + (24 hrs.) (Volunteer no.6)
27. Increased appetite +++ (Volunteer no.7, 8)

CVN01 nosode was found to be safe in healthy volunteers. Immune response was recorded in terms of elevated IL-6 in all the volunteers with a corresponding increase in CD4 count and development of COVID19 antibodies, in some, along with the documentation of mild to moderate, self-limiting clinical symptoms experienced by the volunteers.
Trial 3:A study was carried out using quarantine groups to see the effectiveness of various known homeopathic medicines and the nosode of the present disclosure, against COVID-19 infection. Various homeopathic medicines, which are known to have some effect against viral infection, were administered in combination and individually, as shown in Table 5. illustrates the efficacy of the nosode of the present disclosure against COVID-19 infection rate against placebo and other homeopathic medicines.
Table 5
Quarantine study Result
No. Medicine Number Positive cases Percentage
1 Arsenic album, Bryonia alba, Gelsemium S, Influenzinum 655 18 2.75
2 Arsenic album 30 311 7 2.25
3 Placebo 330 13 3.94
4 Camphora 1M 315 12 3.81
5 CVN01 Nosode 312 5 1.60
Total 2233 59 -

Table 5 shows that on administration of other known homeopathic medicines, the percentage of positive cases (1.29% to 3.81%) are reduced from 3.81% to 1.60%. However, on administration of the nosode of the present disclosure (CVN01 Nosode), significantly lesser percentage (1.6%) of positive cases were reported as compared to placebo and most of the other known homeopathic medicines or combinations thereof. This clearly establishes the efficacy of the nosode of the present disclosure against COVID-19 infection.
Trial 4: Protocols for conducting animal toxicity study
Protocols were established for conducting animal toxicity study for the nosode of the present disclosure. For this, Coronavirus nosode of the present disclosure (labelled as CoviNo) of potencies 15c, 30c and 100cwere prepared from the clinical sample of a patient having confirmed infection of SARS-Cov-2, in accordance with Trial 1, following various guidelines and protocols, at Haffkine Institute, Mumbai.
Study Design:
This study was conducted at a single center in Hyderabad, India, and was designed to examine the toxic response of Coronavirus nosode (labelled as CoviNo) of 15c, 30c and 100c potency, when administered orally to healthy animals.
The study was planned in four parts:
1) Study number 32920: Single dose toxicity study of CoviNo in Swiss Albino Mice
2) Study number 33020: Single dose toxicity study of CoviNo in Wistar Rat
3) Study number 33120: 28 days repeated dose toxicity study of CoviNo in Wistar Rat
4) Study number 33220: 28 days repeated dose toxicity study of CoviNo in New Zealand White Rabbit
Study Population:
Single dose:Study part 1 (no. 32920) and study part 2(no. 33020) were carried out by administering a single dose of 20µL of 15c potency, as shown in Table 6 below.
Table 6
Study no. 32920 Study no. 33020
Animal Swiss Albino Mice Wistar Rat
Age of animals 8-12 weeks 8-12 weeks
Total no. of animals 5 males & 5 females 5 males & 5 females
Dose Single dose of 20µL, thrice in 24 hours for one day Single dose of 20µL,thrice in 24 hours for one day
Potency 15c 15c

Repeated dose:Study part 3 (no. 33120) and study part 4 (no. 33220) were carried out by administering single doses of 20µL, twice daily for 28 days.The animals in each study no. 33120 & 33220 were divided into 4 groups for administering different potencies of 15c, 30c, and 100c potencies, as shown in Table 7.
Table 7
Study no. 33120 Study no. 33220
Animal Wistar Rat New Zealand White Rabbit
Age of animal 6-8 weeks 10-14 weeks
Total no. of animals 24 males & 24 females 12 males & 12 females
Dose Single dose of 20µL, twice daily for 28 days Single dose of 20µL, twice daily for 28 days
The animals were divided into 4 groups for administering different potencies
Potency 0 6 males & 6 females 3 males & 3 females
Potency 100c 6 males & 6 females 3 males & 3 females
Potency 30c 6 males & 6 females 3 males & 3 females
Potency 15c 6 males & 6 females 3 males & 3 females

Assessment:
According to the protocol, the animals were observed for 28 days for signs of toxicity and mortality, based on standard clinical parameters. No mortality or morbidity was observed at any potency.
TECHNICAL ADVANCES AND ECONOMICAL SIGNIFICANCE
The present disclosure described herein above has several technical advantages including, but not limited to, the realization of:
• nosodes for the prevention, alleviation of symptoms and treatment of viral infections
• nosodes that have no side effects
• nosodes that are simple and safe to manufacture
• nosodes that are cost-effective.
Throughout this specification the word “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.
The use of the expression “at least” or “at least one” suggests the use of one or more elements or ingredients or quantities, as the use may be in the embodiment of the disclosure to achieve one or more of the desired objects or results.
Any discussion of documents, acts, materials, devices, articles or the like that has been included in this specification is solely for the purpose of providing a context for the disclosure. It is not to be taken as an admission that any or all of these matters form a part of the prior art base or were common general knowledge in the field relevant to the disclosure as it existed anywhere before the priority date of this application.
The numerical values mentioned for the various physical parameters, dimensions or quantities are only approximations and it is envisaged that the values higher/lower than the numerical values assigned to the parameters, dimensions or quantities fall within the scope of the disclosure, unless there is a statement in the specification specific to the contrary.
While considerable emphasis has been placed herein on the components and component parts of the preferred embodiments, it will be appreciated that many embodiments can be made and that many changes can be made in the preferred embodiments without departing from the principles of the disclosure. These and other changes in the preferred embodiment as well as other embodiments of the disclosure will be apparent to those skilled in the art from the disclosure herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the disclosure and not as a limitation.
,CLAIMS:WE CLAIM:
1. A nosode composition for prevention, alleviation of symptoms and treatment of viral infection, wherein the composition is prepared from at least one biological material selected from the group consisting of:
a. live virus;
b. viral spike glycoprotein;
c. inactivated virus;
d. viral envelope protein;
e. viral nucleocapsid protein; and
f. virus irradiated infected cell lysate.
2. The composition as claimed in claim 1, wherein the viral infection is at least one of coronavirus disease 2019 (Covid-19), Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS).
3. The composition as claimed in claim 1, wherein the biological material comprises at least one of SARS CoV-2 virus, SARS-CoV virus, and MERS-CoV virus.
4. The composition as claimed in claim 1, wherein the live virus is obtained from a clinical sample of a virus infected patient or a viral culture.
5. The composition as claimed in claim 1, wherein the composition has a potency in the range of 1c to 1000c.
6. The composition as claimed in claim 1, wherein the composition is in a form selected from the group consisting of liquid drops, oral tinctures, pills, spray and injectable.
7. A method of preparing the nosode composition for prevention, alleviation of symptoms and treatment of viral infection, as claimed in claim 1, the method comprising the following steps:
(i) obtaining at least one biological material from a clinical sample of a virus infected patient or viral culture;
(ii) processing the biological material to obtain an Original Stock Nosode (OSN);
(iii) diluting the OSN with Water for Injection (WFI) to obtain a diluted mixture; and
(iv) serially diluting and succeeding the diluted mixture with at least one vehicle to obtain the nosode composition.
8. The method as claimed in claim 7, wherein the clinical sample is an oropharyngeal swab of a patient infected with coronavirus disease 2019 (Covid-19), Severe Acute Respiratory Syndrome (SARS), and Middle East Respiratory Syndrome (MERS), and wherein the sample is collected in a Viral Transport Medium (VTM).
9. The method as claimed in claim 7, wherein processing in step (ii) comprises obtaining from the biological material at least one of, live virus, viral spike glycoprotein, inactivated virus, viral envelope protein, viral nucleocapsid protein, virus irradiated infected cell lysate, and optionally diluting in sterile water.
10. The method as claimed in claim 9, wherein the inactivated virus is obtained by heating the live virus at a temperature in the range of 60°C to 70°C for a time period of 20 minutes to 40 minutes or by gamma radiating the live virus.
11. The method as claimed in claim 7, wherein the serial dilution in step (iv) is carried out by maintaining a dilution ratio in the range of 1:99 to 10:90 between the diluted mixture obtained in step (iii) and the vehicle, to obtain potencies in the range of 1c to 1000c.
12. The method as claimed in claim 7, wherein the vehicle is at least one of alcohol and water.