ANTI-HIV DRUG RESEARCH

A cheminformatic search of natural anti-HIV drug HOO-IMM PLUS (A,B,C,D,E)


ABSTRACT

The use of Natural medicinal plant to manage HIV/AIDS has recently gained public interest, many research have been done on the ethnomedicine around the globe. Although there have been no medicine licensed till date, this policy remain an arguable issue in many countries. Plants and other natural products present a large repertoire from which to isolate novel anti-HIV active compounds. In this research work, with HOOIMM PLUS (A, B, C, D, E), an anti viral herb-drug manufactured by HOOTONE REMEDIES, have a composition of 33 different plant species those are found in India, were found to contain anti-HIV active compounds that included diterpenes, triterpenes, biflavonoids, coumarins, gallotannins, galloylquinic acids, curcumins and limonoids etc. They also contain the high phenolic content and the presence of polar substances, such as flavonoids and tannins which are known to possess antiviral activity. These active compounds inhibited various steps in the HIV life cycle. The main objective of this study was to carry out a database survey of literature for plants and their natural products with anti-HIV active compound present in HOOIMM plus. Such a Bioinformatic database survey is an important prerequisite and starting point in the search for novel HIV/AIDS treatments from natural plants.


INTRODUCTION

Natural products remain a prolific source for the discovery of new drugs. The recent data suggests that 80% drug molecules are natural products or natural compound. Studies on source of new drugs from 1981 to 2014 reveal almost half of the drugs approved since 1994 are based on natural products. Indian natural products have contributed towards this “boom” in drug discovery. The drug discovery process from plant is, however a laborious and time consuming process. This research article focuses on the laborious and time consuming process. This research article focuses on the role of natural medicinal plants to manage HIV/AIDS and the related opportunistic infection.

The conventional rediscovery process aims to identify a single, pure active constituent from an active extract and a method to estimate it in the crude drug. The classical example of drug discovery like morphine, quinine, digoxin, etc which replaced the extracts of their respective plants were mostly responsible for harbouring the idea that a single active ingredient must have been responsible for the bioactivity. The drawback of this ideology is that it does not look into the synergy or antagonism characteristics present in the mixture. Apart from this some constituents may also possess other diverse activities. This factor is confirmed by several examples reported in literature where the ascribed pharmacological activity of the extracts could not be matched with that of the isolated pure compounds. Most of the newer work on medicinal plants is mostly the rediscovery of effects known for a long period of time at cellular and molecular levels. The uncertainty of earlier studies is obvious in case of biological activity because of the lack of standardization technique or instance where even if present were in a primitive state.

The natural plant medicine has a very long term history of usage in a number of disease and disorders, however, the main constituent mainstay and the mechanism of action being unclear. But recently, it has been suggested that drug discovery should not always be limited to discovery of a single molecule and the current belief “one disease-one drug” approach may be untenable in the future and that rationally designed polyherbal formulation could also be investigated as an alternative in multi-target therapeutics and prophylaxis. Development of standardized, safe and effective herbal formulations with proven scientific evidence can also provide an economical alternative in several disease areas. Still some pro's and con's need attention for improvement of natural medicines.

HIV/AIDS-related diseases remain one of the leading causes of death globally. According to UNAIDS, the number of people living with HIV/AIDS worldwide was estimated at 35 million. The current antiretroviral drugs have many disadvantages including resistance, toxicity, limited availability, high cost and lack of any curative effect (Vermani and Garg, 2002). These shortcomings of conventional ART continue to open new vistas in the use of ethnomedicinal plants and other natural products for the management of HIV/AIDS.

In many countries, the inclusion of anti-HIV ethnomedicines and other natural products in official HIV/AIDS policy is an extremely sensitive and contentious issue. It is sensitive because anti-HIV ethnomedicines and other natural products can easily become a scapegoat for denial and inertia to roll-out ART. It is also contentious because in various resource-poor settings, government-sponsored ART programmes discourage the use of traditional medicines, fearing that the efficacy of antiretroviral drugs may be inhibited by such natural products, or that their pharmacological interactions could lead to toxicity. Reliance on anti-HIV plants and other natural products can also lead to poor adherence to ART (Langlois-Klassen et al., 2007). Thus, many governments still have contradictory attitudes towards the use of anti-HIV plants and other natural products in the management of HIV/AIDS, discouraging them within ART programmes, and supporting them within other initiatives of public health and primary health care.

As early as 1989, the World Health Organization (WHO) had already voiced the need to evaluate ethnomedicines and other natural products for the management of HIV/AIDS: “In this context, there is need to evaluate those elements of traditional medicine, particularly medicinal plants and other natural products that might yield effective and affordable therapeutic agents. This will require a systematic approach”, stated a memorandum of the WHO (1989).

The objective of this study was to carry out a database survey of literature for plants and other natural products with anti-HIV active compound present in HOOIMM PLUS.

a Bioinformatic database survey is an important prerequisite and starting point in the search for novel HIV/AIDS treatments in natural plants. However, further studies are needed to determine their interactions with current regimes of antiretroviral drugs. More clinical trials of candidate drugs developed from these novel compounds are also encouraged.


METHODOLOGY

The different plant species with their active HIV compound were searched in PubMed Central, the United States of America National Library of Medicine's digital archive of biomedical and life sciences journal literature. During the literature search which lasted 3 months, between 300 journal publications were reviewed. Wherever possible, families and species of plants and other natural products, their active compounds and modes of action, were Evidence of use of plants and other natural products against HIV/AIDS was kept unrevealed to maintain the term and policy of pharmaceutical company (HOOTONE REMEDIES), so different codes were given for different active constituents.

Table 1.1: Showing Mechanism of action of various active constituents found in HOOIMM plus.


DISCUSSION

Several chemical compounds were found to interfere with HIV entry into cells while other were active against HIV reverse transcriptase, integrase, protease, and general replication. Most of the entry inhibitors stopped the spread of HIV among cells. Some of them binds to glycosylated viral envelopes blocked HIV-1 entry into cells. A compound isolated targeted gp120 proteins and blocked fusion of HIV-1 to lymphocyte. A crude drug inhibited HIV-1 gp120 binding to CD4 cells, inhibited the binding of gp120 to cells expressing CXCR5 receptors. Inhibited cell-to-cell transmission of HIV-1inhibited HIV-1 entry into lymphocytes. Three different chemical compounds were known to be active against HIV reverse transcriptase (Table 1). Three active compounds were observed to be HIV protease inhibitors. Two active compound were observed to be HIV integrase Inhibitor. Some active compounds were found to inhibit syncytia formation, a property of HIV that makes infected and healthy CD4 cells to fuse and form one giant cell. Many active compounds were known to inhibit general HIV replication. Some plant-derived compounds were reported to possess activities against HIV-related symptoms.


CONCLUSION

The literature survey revealed several anti-HIV active compounds such as terpenoids, coumarins, polyphenols, tannins, proteins, alkaloids, and biflavonoids that inhibit various steps of the HIV life cycle. These active compounds were isolated from 33 Plant species. Phylogenetic analysis and other bioinformatics tools may shed light on unidentified but related plants and other organisms that may contain similar active compounds. Primary data of known active compounds and mechanisms of action were available from studies. Pharmacological interactions of unknown active ingredients from herbal medications remain a source of great medical concern. Throughout the survey, it was clear that although several medicinal plants, most of the research on screening of plants and isolation of active compounds was carried out elsewhere in Asia, Europe and the Americas. in vitro tests against HIV, and mechanisms of action is highly needed. There is also an urgent need to fast-track HIV/AIDS clinical trials of candidate drugs developed from novel compounds isolated from plants and other natural sources. This will ensure that the millions of people that require HIV/AIDS treatment will have access to newer, more effective, and less toxic drugs.


REFERENCES
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Research & Development of the Unani Anti-HIV Drug HOO-IMM PLUS
The formulation of the drug is made according to the Unani system of Medicine and approved from FDA (Food and Drug Administration), Mumbai, India. And the compositions of the formulation are purely herbal, standardized according to the Pharmacopoeia of Herbal Extracts. The R&D of this particular drug initially started as a treatment for the asymptomatic and symptomatic HIV associated diseases and AIDS related complex. And later with the considerable improvement in the patients noted in response to the therapy more scientific and controlled studies were undertaken with the help of modern molecular diagnostic services from reputed and a well-equipped laboratory Reliance Life Science. And the records of the tests were well maintained in the form of soft and hard copies representing R&D data pertaining to the treatment. The formulation has undergone scientific studies for the two most important tools for analyzing the effectiveness of the drug; they are a) Invitro Studies and b) Invivo Studies. Also the formulation has successfully gone through a toxicity test and certified for free from heavy metals, steroid and animal origins, lead, arsenic, mercury etc.

Individual action of the ingredients of Anti-HIV drug HOO-IMM PLUS:-

HOO-IMM PLUS (A)
  1. Saffron (Zafran) Pg292* - Restorative, builds up body's defence mechanism thereby strengthening the immunity system considerably.
  2. Orchis Latifolia (Salab Misri) Pg147* - Tonics for blood, vital energy and vital essence.
  3. Pipper Longum (Phil Phil Daras) Pg 119* - Strengthens up spleen, lymphatic glands. Activates the endocrine glands of the body.
  4. Peganum Harmala (Hurmul) Pg 61* Increases level of cellular immunity; inhibits replication of viral activities.
  5. Pipper Nigrum (Kali Miri) Pg 336* - A Pulmonary tonic, important in long term strengthening of the lungs.
  6. Withania Somnifera (Asgandh) Pg 64* - A Nervine tonic, helps relieve associated psychological tension or anxiety.
  7. Sida Cordifolia (Beej Band) Pg 140* - A Diuretic, relieves the congestive nature accompanied by water retention.
  8. Pearl (Moti) Pg345* - Increases amount of calcium, iodine and phosphorus in the body.

HOO-IMM PLUS (B)
  1. Pistachia lentiscum (Masthagi) Pg339* - Tonics for blood, vital energy and vital essence.
  2. Hollerrhena Antidysenterica (Inderjo Talkh) Pg79* - Anti-diarrheal relieving dysenteric symptoms.
  3. Emblica Officinalis (Amla) Pg 49* - Strengthens up lymphatic glands by promoting lymphocyte transformation.
  4. Arista Lochia (spp) (Zaravant) Pg 140* - An Anti-microbial, helps the body control and clear bacterial infection.
  5. Zingiber Officinalis (Zanjabeel) Pg 55* - An Expectorant remedy, helps to maintain aminimum build up of sputum in the lungs.
  6. Pistachia Vera Linn (Gul Pista) Pg122* - Enhance renal functions.
  7. Punica Granatum Linn (Gul Anar) Pg75* - Prevents degeneration of renal tubes & nephrons

HOO-IMM PLUS (C)
  1. Santalum Album (Sandal) Pg 166* - Enhances new cells regeneration, cleans up dead cells & prevents pus formation.
  2. Similex China Linn (Chob Chini) Pg167* - Accelerates protein synthesis, thus stimulating cell regeneration.
  3. Piper Cubeba (Kabab Chini) Pg 263* - Accelerates protein synthesis, thus stimulating cell regeneration.
  4. Swertia Charata (Chiraita Shirin) Pg160*- Detoxify the impure blood.
  5. Borage Officinalis (Gav Zuban) Pg296* -Increases level of cellular immunity; inhibits growth of tumor cells.
  6. Centaurea Behen (Behman Surkh) Pg108* - Anti-neoplastic, prevents development & maturation of malignant cells.
  7. Lavendula Steochas (Istukhudus) Pg63*- Strengthens up spleen, lymphatic and endocrine glands.

HOO-IMM PLUS (D)
  1. Delphinium Denudatum (Jadhwar) Pg 359*- An Anti-microbial, helps the body control and clear bacterial infection.
  2. Planta Goovata (Isabgol) Pg62* - Promote bowel movement through stimulation of bile production in the liver.
  3. Chena Podium Album (Bathwa) Pg 93* - Circulatory Stimulant, promotes the circulation of blood and thus oxygen availability for vascular resistance,
  4. Artemisia Absinthium (Afzantheen) Pg 66*- A Vascular Tonic, helps nourish the tissue of the arteries and veins. Prevents against hardening of fibrous muscles of the Heart.
  5. Arista Lochia (spp) (Zaravant) Pg 207* - An An Anti-spasmodic, eases the muscle spasms, cramps that are the immediate cause of pain.
  6. Terminalia Arjun (Arjun) Pg 57* - Cardiac & Vascular Tonic, supports the tissue of the cardiovascular system, maintaining flexibility and tones affected vessels.
  7. Cinnamomum Zeyanicum (Dalchini) Pg181* - This drug rectifies all mucus membrane in the body after reducing the virus.

HOO-IMM PLUS (E).
  1. Swertia Charata (Chiraita Shirin) Pg160*- Detoxify the impure blood. Antipyretic subsides persisting fever.
  2. Kawal Gatta (Nelumbu Nucifera) Pg283* - Relieves congested & catarrhal conditions of liver and controls secretion of bile.
  3. Meba Azadrach (Bakain) Pg 100* - Anti-tumor immuno-surveillant system, intensifies phagocytosis of reticulo-endothelial systems.
  4. Rubia Cordifolia (Majeeth) Pg 335*- Accelerates protein synthesis, thus stimulating cell regeneration.
  5. Valerina Officinalis (Balched) Pg 91* - Hepato-protective, detoxifying the liver with the deleterious effects of daily encounters with air-water and food-borne toxins.
  6. Chena Podium Album (Bathwa) Pg 93* - Circulatory Stimulant, promotes the circulation of blood and thus oxygen availability for vascular resistance,
  7. Berberis Vulgaris (Dar Hald) Pg 182* - Anti-microbial, facilitates the body ridding itself of pathogens present reducing inflammation and its resulting symptoms.
HIV AIDS treatment is not complicated, knowing what drugs you are taking, how they work against HIV, and why it is so important to take them as prescribed (on time, with or without food, etc.) can really help in the fight against HIV. HIV AIDS treatment is safer, if your treatment consists of toxic free, side-effect free medications. HIV AIDS treatment becomes more comfortable, if your treatment doesn’t ask for switching on to new drug combination because of drug resistance. HIV AIDS treatment is not complicated, knowing what drugs you are taking, how they work against HIV, and why it is so important to take them as prescribed (on time, with or without food, etc.) can really help in the fight against HIV. HIV AIDS treatment is safer, if your treatment consists of toxic free, side-effect free medications. HIV AIDS treatment becomes more comfortable, if your treatment doesn’t ask for switching on to new drug combination because of drug resistance.