How to deal with Recurrent infection serge of corona virus.

How to deal with Recurrent infection serge of corona virus.

Last years in 2020 and 2021 we have faced lock down to protect ourselves from corona virus and its life threatening infection. Many of us went through vaccination and even after vaccination lives were lost due corona infection.

Corona infection acts on the blood and blood vessels, triggering interleukin flair that caused damage to lungs tissue and due to embolism, and subsequent events deaths occurred.

Again it is found that after gap of almost one and half years after successful defeating omicron variant serge again the corona virus infection cases are increasing.

In a latest finding in a research conducted by national institute of health it is found that the person infected with corona virus develop several defects so that the other disease overweighs on the health conditions.

The vaccines are found to produce lesser protective effect in person with earlier infection history and has not received any vaccination. In the study it is found that person who are never infected in them vaccines produced strong protective effect, compared to the person who was previously infected with corona virus. (reference 1)

The person affected with diabetes and higher cholesterol are at high risk from the current serge of corona virus.

Therefore, in order to survive the newer corona infection Yoga Practices should be adapted and practiced daily basis, yoga has found to strengthen immunity.

Treatment for COVID 19, due to the increased number of Omicron (B.1.1.529)   Variants of concern. Reference (2)

In Feb 2023 The National Institute of Health of the United States has published a guideline for providing Treatment for COVID 19, due to the increased number of Omicron (B.1.1.529)   Variants of concern.

The guideline is an eye opener, when NIH mentioned in it that the recently developed monoclonal antibodies treatment for treatment of SARS-COV-2 may not be effective against the Omicron (B.1.1.529).Therefore it has advised in its guideline that doctors should also give remdesavir intravenous dosage to out patients as well, the use of remedisavir was limited to hospitalized patients, while NIH recommend to make use of the remedisavir in outpatient as well along with  NIH in its guideline has also recommended use of only one monoclonal antibody Sotrovimab 500 mg Intravenous as a single infusion (AIIa) immediately within 10 days of symptoms onset.

1.Sotrovimab 500 mg Intravenous as a single infusion (AIIa) immediately and within 10 days of symptom onset.

2. Remdesivir 200 mg intravenous on day 1, then 100 mg once daily on Days 2 and 3 (BIIa) initiated as soon as possible and within 7 days of symptom onset.

Remedesivir intravenous injection requires for three consecutive days therefore it's one of the concerns for outpatients.  

Due to the greater variation in spike protein due to variation in gene sequence the antibodies which were developed with earlier sequence viz bamlanivimab plus etesevimab and casirivimab plus imdevimab, may not be effective against the Omicron (B.1.1.529). Therefore, if at all someone makes use of them, it should be kept in mind that they may not work.

Reference:

(1) Pharma Times

(1) https://www.nih.gov/news-events/news-releases/sars-cov-2-infection-weakens-immune-cell-response-vaccination

(2) https://www.covid19treatmentguidelines.nih.gov/management/clinical-management-of-adults/nonhospitalized-adults--therapeutic-management/

Which are the currently available medicines for treating HIV infection ? What is HAART ?

  Which are the currently available medicines for treating HIV infection ? What is HAART ?

There are following class of Medicines available so far for treatment of HIV infection.
HAART is made up of different kinds of drugs comprising from following categories:

1. Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
2. Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs)
3. Protease Inhibitors
4. Fusion Inhibitors
5. Integrase Inhibitors
6. Entry Inhibitors

7. Capsid formation inhibitors.
7. Combination Drugs

Here is the detailed list of drugs which are approved by US FDA.
These drugs are mentioned here just for the sec of education and purely for information purpose only , drugs are referred here for reference purpose only for research institutes ,universities and research scientists.

One should not take any drug without consulting his or her doctor , they (doctors) prescribe drugs keeping in view all the side effects and benefits of a drug if there are more harmful side effects which may prove fatal to a patient than actual benefit then such drugs are avoided , hence one should listen and follow doctors instruction regarding medication.

 First Brand name is given and in the bracket generic name of the drug with its abbrivation is provided)
*Nucleoside Reverse Transcriptase Inhibitors (NRTIs)  ---
Combivir (Lamivudine and Zidovudine)
Emtriva (Emtricitabine FTC)
Epivir (Lamivudine 3TC)
Epzicom (Abacavir and Lamivudine)
Hivid (Zalcitabine Dideoxycytidine ddC )
Retrovir (Zidovudine AZT or Azidothymidine, ZDV)
Trizivir (Abacavir, Zidovudine and Lamivudine)
Truvada (Tenofovir Disoproxil and Emtricitabine )
Videx (Didanosine , ddl, Dideoxyinosine)
Videx EC (Enteric Coated Didanosine)
Viread (Tenofovir Disoproxil Fumarate, TDF )
Zerit (Stavudine d4T)
Ziagen (Abacavir Sulfate, ABC)

*Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Intelence (Etravirine)
Rescriptor (Delavirdine DLV)
Sustiva (Efavirenz)
Viramune (Nevirapine)

*Protease Inhibitors
Agenerase (Amprenavir APV)
Aptivus (Tipranavir TPV)
Crixivan (Indinavir IDV, MK-639)
Fortovase (Saquinavir (no longer marketed))
Invirase (Saquinavir Mesylate SQV)
Kaletra (Lopinavir and Ritonavir LPV/RTV)
Lexiva (Fosamprenavir Calcium FOS-APV )
Norvir (Ritonavir RTV)
Prezista (Darunavir)
Reyataz (Atazanavir Sulfate ATV)
Viracept (Nelfinavir Mesylate NFV)

*Fusion Inhibitors
Fuzeon (Enfuvirtide T-20 )This medicine is a shot.

*Multi-Class Combination Drugs
Atripla (Efavirenz, Emtricitabine,and Tenofovir Disoproxil Fumarate)

*Integrase Inhibitors
Isentress (Raltegravir)

*Entry Inhibitors
Selzentry (Maraviroc)

* Viral Capsid formation inhibitor drug Lenacapavir.

It is required to form a combination of drugs from almost all class of drugs listed above so that the virus multiplication and count is brought under control.
This is called Highly Active Antiretroviral Therapy. (HAART)

Source:

https://timesofpharma.com/treatment-of-hiv-medicines-side-effects-contraindications/

Pharma Times

FDA approved drugs for HIV treatment

------------------------------------------------------------------------------------

Last updated: 15-Nov-2010

New Class of Antiretroviral Capsid formation inhibitor that provides option for treatment to Multi Drug Resistant HIV 1 Infection

New Class of Antiretroviral drug Lencapavir to provide lifesaving remedy for HIV infected people having Multi Drug Resistant HIV 

HIV virus can infect the human body through a mechanism of infection, and it reproduces in the human body increasing its number to lacs of viral copies in blood, and making lives of infected persons difficult. 

For the increased level of HIV Viral load doctors have to prescribe heavy dosage of (antiretroviral drugs) AVRs , which make the situation further complicated because heavy doses of AVR further complicate the situation by developing multi drug resistant HIV-1.

There are several different Class  medicines which were available for HIV (< Refer here)

These medicines are developed by studying the process of infection stages, and there are medicines available against HIV for inhibiting growth of HIV (replication) which inhibit these particular stages in the infection process.

One point in the viral multiplication stage was not having any medicine, that is viral capsid (viral protein coat) formation, which would inhibit the same, that is synthesis of viral capsid of HIV. With the non-availability of the medicines acting at this stage, drug resistance was getting developed with repeated prescription of the same class of drugs. 

On 22-12-2022 US FDA approved Lenacapavir a new drug which is capable of inhibiting HIV-1 viral protein coat, the capsid formation. This is a very important stage in the growth of the HIV virus in the human body. This drug Lenacapavir inhibits the synthesis of HIV-1 viral protein coat, the capsid formation.

Lenacapavir when combined together with drugs which are acting at different stages of infection and replication process, these all together stopes reproduction of HIV in human body, thereby bring the HIV viral load under control, some patients when given Lenacapavir along with other combination drug, have brought down the HIV viral count to undetectable level. The medicines combined together to achieve the desired result of bringing down HIV Virus blood count are called combination therapy for HIV.

Lenacapavir is expected to provide good results in bringing down HIV-1 viral count in patients with multi drug resistant HIV.

Drug Linacapavir is required to be given once in six months a subcutaneous injection, every after 6 months along with other combination therapy medicines.

Mechanism of action of Lenacapavir: 

Lenacapavir inhibit protein synthesis of Viral Capsid thereby inhibit HIV virus replication and growth.

Advertisment: Pharmaguideline 

Source: USFDA approved Lenacapavir  https://timesofpharma.com/lenacapavir-new-antiretroviral-drug-for-multi-drug-resistant-hiv-infection-approved-by-usfda

Different Class of Antiretroviral drugs

https://bvwaghmare.blogspot.com/2010/11/which-are-currently-available-medicines.html

Pharma Times

Opoidal drug should be contraindicated in COIVD 19

Dextromethorphan a drug which is an analog of morphine and consist the main maopholine ring in its molecule which is also part of all opoid drugs.

It is found that the Sigma1 sites on the viral particles are bind with Dextromethorphan in a manner that helps virus to replicate.

Also the lysosome which impart cellular Immunity by embibing and dissolving viral particles, formed are smaller in size so that they are not effective against SARS-COV-2 viral particle vessicals. 

Also there are some research findings on Opoid drugs usage and high mortality rate in patients given opoids for treatment of pain management.

Opoids are consided to be suppressing immunity ER lysosomal cellular protection mechanism is hampered by the Opoids.

Therefore treatment of SARS-COV-2 Positive patients drug that contains dextromethorphan or any opoidal anasthetic drug should be avoided, use of such agent should be done based on risk based approach.

On the other hand drug Haloperidol which is used in treatment of mental disorder is found to be blocking virus replication therefore this drug may be a good candidate for the treatment of SARS-COV-2 .

Also these studies require Clinical evaluation through Clinical trials.

How ever looking at the reserch outcome it is recommended that dextromethorphan containg cough Syrup should be avoided for COVID 19 positive patients.

There are other Cough Syrups containing, Ambroxol, Guaphenasin, Bomohexine Hydrochloride Contaning Cough Syrups, it should be started 5 ml Twice a day for positive patients even if there is no cough because it take three to four dose to show mucolytic activity, mucolytic activity is also hamper Virus growth and protect from damage to lungs due to coughing action.

Dextromethorphan should be contraindicated for COVId 19

Reference: 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509052/#!po=32.7778

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214617/

Repurposing of existing Drugs in prevention and mitigation of Novel Corona Virus 19

Which are best candidates from existing drug molecules for use as antiviral drug against Novel Corona Virus 19.

1) Existing drugs which hold molecular similarities and properties which can potentially exhibit antiviral activity in treatment of novel corona virus 19 are listed below.

2) Diethylcarbamazine (DEC): Diethylcarbamazine(DEC) as Antiviral or in the therapy of novel corona Virus.

Diethylcarbamazine (DEC) once was studied for enhancing the antibody generation in patients infected with HIV, and it is found that it has good antiviral activity as well.
Its molecular structure is makes it potential competitive inhibitor for pyrimidine bases  during transcription. Also a negative feedback mechanism can increase the antibody well before the virus becomes harmful to the lungs tissue.
a dose of 10 mg / per kg/ day will be useful in treatment of Novel Corona Virus19 and management of covid19.

Diethylcarbamazine 

Abstract from An available study conducted by Kitchen Lynn W. M.d, Harvard University and later which was patented is provided below.

1) Protease inhibitors Drugs that inhibit nucleotide by presenting themselves as competitive inhibitor of RNA elongation and protein synthesis by inhibiting Uracil, Cytocin, and Adenine neucliotides,  in order to achieve this drugs those resemble in the structure orientation to Uracil, Cytocin, and Adenine nucleotide to be chosen

Following drugs are already in existence and approved as antiviral drugs, and hold many structural similar portions in their molecule which has capability to present that portion to polymerase enzyme and bind bases in the RNA and DNA during the process of translation and protein synthesis.

One Combinition
1) Lopinavir.(LPV)
2) Ritonavir. (RTV)
3) Saquinavir (SQV) or  Cidofovir

       +
2) Diethylcarbamazine (DEC)

These drugs to be taken in combination all together as
One dose L/R and another of C will ensure that the viral RNA synthesis is provided competitive drug molecules for competitive inhibition of RNA elongation.

Following is the detail chart with structural similarity identification for selection of drug candidate is done for Protease inhibitor category of drugs.

1) Protease inhibitors in existing class of drugs used in the treatment of HIV infection.
1) Lopinavir.(LPV)
2) Ritonavir. (RTV)
3) Cidofovir (C)

First dose in morning Combination of  1) Lopinavir.(LPV) + 2) Ritonavir (RTV)  Combination with 3) Saquinavir (SQV) or 3) Cidofovir

+ Diethylcarbamazine (DEC) 10 mg/kg body weight.

Referance: https://patents.google.com/patent/US4900548A/en
Kitchen Lynn W. M.d, Harvard University

Steps in prevention of Corona Virus 19 spread

How to prevent spread of Corona Virus 19 ?

Following steps will help to save lives of millions of people from getting SARS COV 19 infection.

An Alcohol or Isopropyl Alcohol based hand sanitizer may not be so effective as  that of Dilute  Solution of bleaching powder.
Prefer Dilute solution of bleaching powder allow it's contact for minimum 10 minutes.

1.Keep yourself away from a person by minimum 6 feet when you are outside of your home.

2. Currently self quarantine is very important in preparation of spread of Corona Virus 19.

3. Don't  go out of door of your home.

4. Don't touch outer surface of door of your house or  ATM key pad, lift keypad, Staircase handrail, wash your hand immediately with bleaching powder solution or hand sanitizer.

5.Hand Sanitizers may not be available in market therefore make use of bleaching powder which kills all types of Viruses at concentration of 200 ppm and more.

6.Make Chlorine solution by dissolving 4 to 5 %  bleaching powder in water and keep in your house for washing hand and outer surface of door with dilute solution of bleaching powder. Wash door bell, door foot steps corridor with bleaching powder solution every after 6  hours in day time.

7. Use nose masks when you go out : Nose masks of virus free filter pore size are not available in market. You can make it at home by stitching from keep old cloths and keep double layer of absorbent cotton inside mask now they are  now as ofgood as N95 grade.

 8.Wash hands with bleaching powder solution or hand sanitizer and sprinkle water on nostrils when you go inside your house from outside.

 9.Doctors who come in contact with patients. Swab your hands and lips with Povidone Iodine ointment , (Cipladne, Wokadine, Betadine). During handling of COVID postive patient. Swab your inner surface of nostrils with above mentioned Povidone Iodine ointment.

10.Take care of your neabour by sprinkle bleaching powder in corridor. Spread this technical information to everyone.

11. Stop spreading Corona Virus by not spiting in open make use of wash basin and run water and wash it.

12. Don't do Shake hands. Don't hug.

13. Decontaminate Cloths of  an Infected person by diping in to  of dilute solution of potassium permanganate freshly prepared solution. Or Bleaching powder allow minimum contact time of the potassium permanganate solution or bleaching powder solution for 10 minutes.

15. Large community of people in India live in slums where they use common toilet, so every 4 hours spread bleaching powder in toilets
Use nose mask while using common toilet, wash hands with bleaching powder solution. Keep plenty of bleaching powder in such common toilet place.

16. Do Yoga everyday. Yoga boosts immunity and protect from disease progression and will save your life.

Medicines to be used are recommended to doctors only. Avoid self medication.

Following Medicines to be used. In combination as combination therapy.

1. (Lopinavir +Ritonavir + Saquinavir) + Cidofovir


As viral load control measure.

To ease the lungs tissue damage, , use Chlorphenarmine maliate  or Montelukast Sodium.

Dexamithasone

Plasma therapy :
Plasma of a patient who has recovered from infection and tests negative in PCR test to be taken and used to treat a patient who is critical.
Extract plasma in respective blood group wise and keep it for treatment for same blood group patient.


References: 
https://www.ncbi.nlm.nih.gov/pubmed/9403252

https://www.cdc.gov/vhf/ebola/clinicians/non-us-healthcare-settings/chlorine-use.html

Prevention and mitigation strategy for novel coronavirus infection

How to prevent corona virus infection spread.

Following techniques will provide significant protection from protecting an individual from getting COV19  infection even while living with person infected with Novel Corona Virus.

These techniques are not adapted in china and other countries hence the spread and lethal impact of the outbreak is very huge and life threatening.
In emergency situations masks and sanitisers will not be available since almost all hand sanitizer are Isopropyl alcohol or ethyl alcohol based hand Sanitisers in critical situations they will not be available to general public . 
Therefore alternative decontaminating agent which are not much discussed and hand made cloth masks too can be prepared which can prevent virus transmission.

1)Prevention: (P)

P1) Use Nose mask that contain activated charcoal bed :

How to make activated charcoal Mask ? 

Take adsorbent cotton, make a thin pad by spreading it in thin layer, air should easily pass through this, place thin layer of activated charcoal, make such two layers of activated charcoal and cotton. Take porous cloth and cut it in mask shape, keep these two pads over it, fix it by stitching or by making a bag like, or pocket in mask, and use these mask.
Before making mask use clean cloth, it should be disinfeceted by dipping inside solution of a disinfectant. 

Activated charcoal pads can be replaced in two days with fresh one.

P2) Sanitation and decontamination:
Bleaching Powder Solution :

Very effective and cheaper and widely available sanitizer is bleaching powder . It contains chlorine and it is very powerful decontaminimaging agent it is active against all sorts of Viruses and bacteria.
Make 3 To 5% solution of bleaching powder in water and use this as decontaminimaging agent or as sanitizer.
Sprinkle this solution over the articles and body part which you feel that might be potentially contaminated.
Make continuous thin film of bleaching powder solution over hand or article allow the chlorine react with contamination. It will take about 5 to 10 minutes.
Avoid contact of bleaching powder solution with eyes. Bleaching powder is widely available and is very reliable as disinfectant for virus contaminants.

Dilute solution of Potassium Permanganate:

Dilute solution of Potassium permanganate or sodium Hypochlorite solution to disinfect the flooring and the tabletops, and hand in event of potential risk of patient of corona virus is around the area.
How to make Chlorine disinfectant.
Dissolve about 200 ppm to bleaching 250 ppm powder in water and use 

Make very dilute solution of Potassium permanganate, and use it freshly to decontaminate hand, use as hand wash, higher concentration may cause skin irritation, avoid contact with eye.

Use goggles or spectacles, to protect eyes, decontaminate spectacles with the dilute solution of potassium permanganate.

To decontaminate surrounding use fogger machines or any suitable equipment that generate fumes of the chemical.

Following chemicals can be used to decontaminate infection in environment and in surrounding

1. Spread bleaching powder in surrounding, since its widely available its best decontaminating agent.
2. Use H2O2 (Hydrogen Peroxide) in fogger and fog the area where a potential contamination iso.
3. Wipe the flooring and wall and handrail table top with chlorin water, prepared out of bleaching powder. Use freshly prepared chlorin water from bleaching powder.

4. Following antimicrobial preparation can be used to decontaminate. Hands, and infected material.

a) Iodine solution, ( Cipladin, Betadine, Wokadine)

b) Mecetronium ethyl sulphate (SterIllium )

c) Silver nitrate solution freshly prepared, d) Iso propyl alcohol, e) Ethyl Alcohol, f)chlorhexidine gluconate containing solutions.

Which body parts to protect.

Avoid touching your eyes, lips and tongue, nostrils, wear spectacles.

Use nose mask containing activated charcoal as described.

As far as possible keep lips closed, avoid speaking without mask.

Protect Ears, a small cotton plug can be used which should be replaced as and when required.

P3) How to protect viral entry in to body 

 Use occlusive methods.

1. White soft paraffine (Vassaline) is a good occlusive agent, nostrils should be covered from inside with thin layer of white soft paraffine which will protect from viral entry in to body.
2. Silver sulfadiazine creams can also be used as occlusive barriers inside the nostrils.
3. Creams containing chlorhexidine gluconate.

Do gargles frequently with water, if there are patients surrounding, use solution of chlorhexidine gluconate to do gargles.

Treatment and medication:

Currently there is no medicine available which is approved by FDA for treatment of novel coronavirus.

Following drugs are recommended after study of the medicinal chemistry and mode of action of the available drugs.

Following suggested medicines best suit for treating the novel corona virus infection.

1.Urgent ayurvedic remedy:

Drink 50 ml of water in which small pinch of Haldi (curcuma longa) is added do not boil after addition of haldI.

Drink this three times a day, do not exceed this.

Haldi contains potent cytotoxic curcumin, which will help in prevention of virus replication in body.

2. Drug for treatment:  (recommendation for medical professionals only)

Following drugs should be used in treatment in combination

A) Combination therapy. (Tetracycline Or Chloroquine + Proteases inhibitors+ Amantadine)

1)Tetracycline + Amantadine+ Protease inhibitor drugs.

In combination with any one drug in following list of protease inhibitors.

Protease inhibitor drugs
Protease inhibitor drugs.
atazanavir (Reyataz)
darunavir (Prezista)
fosamprenavir (Lexiva)
indinavir (Crixivan)
lopinavir/ritonavir (Kaletra)
nelfinavir (Viracept)
ritonavir (Norvir)
saquinavir (Invirase)
tipranavir (Aptivus)
atazanavir/cobicistat (Evotaz)

darunavir/cobicistat (Prezcobix)

B) Combination therapy with (Tetracycline Or Chloroquine+ 5 Flurouracil +Amantadine)

C) Combination Therapy with (Tetracycline +Amantadine+ Any one drug from Nonnucleoside RT inhibitors)

Nonnucleoside RT inhibitors Drug 

1) Rilpivirine

2) Etravirine

3) Delavirdine, DLV

4) Efavirenz, EFV

5) Nevirapine, NVP

Drugs are cytotoxic hence should be taken only after prescription of a medical practitioner.

2.Serum Therapy:

Serum to be separated from infected and cured person and to be used as antibody treatment to person who has got infection recently.

Survival trick:

One can survive even after getting corona virus infection in event, person has got strong lung capability, and has got good immune power.

Yoga is found to be boosting the interlukin 2 system that improves the immunity, therefore yoga will be very important part for patient for survival.

Following Yoga therapy is very important

1)     Yogic cleansing methods

1.      Nostril wash: Yoga kriya :  Neti kriya to be done In event of exposure threat.

2.      Gastric Cleansing : Yoga kriya, Jal Dhauti. In event or after the suspected infection.

3. Boosting immunity :  

Following Yoga Kriyas are very effective in boosting immunity against viral infections, we had done experimentations on HIV patients which we could observe that the body immunity get improved with yoga kriyas.

Shri Ambika Yoga Kutir Thane can be referred for this.

1.Regularly perform : Kapalbhati.

2.Regularly perform Pranayam Kriya: Ujjayi.

3. Omkar Sadhna: Provides heat energy in body due to its unique sound vibrations, boosts immunity.

Not every patient die due to viral infection, person with lower immune power and week lungs are susceptible hence lungs capability can be improvised with yoga, Kapalbhati, and Pranayam kriyas.

Don’t do pranayama, Kapalbhati, Ujjayi kriyas in open environment, but should be done in closed room with clean environment.

Self quarantine:

In event someone is tested positive doctor should confirm with confirmation test PCR technique for presence of viral RNA.

Ensure that you do not spread contamination to others, stay at home, use nose mask and follow the advise provided above.

Do not panic one can survive and get cured from corona virus infection, your fear will bring down the immunity which might be lethal for you, therefore regular yoga practice must be followed.

How to make activated charcoal: 
Activated charocal is easily available in market in good qty.
If its not available it can be made by incernating coconut shels at temprature 900 Deg Celcius.
While temprature is coming down it is spryed with hot steam.
So one should have a steam generating equipment, after taking out the charcoal from the heater or burner, slight steam is exposed over the charcoal.

For Yoga techniques to perform see:

Kapalbhati :   https://www.youtube.com/watch?v=8lZdyOZYiGU

Ujjayi :   https://www.youtube.com/watch?v=L-tfoU_K7so

Omkar :  https://www.youtube.com/watch?v=z_i-mb3XZFM

Following link for Information: How yoga is effective in lowering HIV viral load.

https://www.youtube.com/watch?v=owCj1coWROY#action=share 

B V Waghmare (2020). Prevention and mitigation strategy for novel coronavirus infection https://bvwaghmare.blogspot.com/ : DOI

HIV vaccine by step by step immunization strategy

Antibodies isolated from HIV positive individuals were successful in preventing proliferation of HIV in animal, while it was not preventing HIV in the infected individuals. Advertisement Pharma Guidelines 

What is that difference that antibodies work against HIV in animal model, is now key towards development of a successful vaccination program against HIV.

HIV virus infect B cells which impart protection by developing immunity against any kind of infection in our body. HIV infects and destroy B cells in our blood. Also HIV change genetic material, DNA of infected human B cells and use these cells for making copies of new HIV virus.

Why vaccine is not completely developed so far because HIV changes its outer protein coat sequence, frequently so that a vaccine against protein coat of HIV is not successful, it may work in one individual while it may not work in other.

How ever there was a finding that Antibodies produced in people which are infected with HIV can protect animals from developing HIV infection and disease AIDS.
Therefore it is possible to develop a vaccine which will work in human model as well.

Team of scientists working with NIH have found a way for developing a successful vaccine against HIV, by combining step by step stimulation by combining three different proteins which will work as antigen and elicit immune response against HIV.

1) VRC01 antibody
2) eOD-GT8 60mer
3) BG505 SOSIP

Combining above proteins for immunization in step by step manner may protect human against HIV infection.

1) VRC01 are antibodies which binds with trimeric gp120 region and inhibit attachment of virus to human B cells.
2) BG505 SOSIP: Are two more similar kind of protein which binds with HIV and neutralize its ability to infect B cells.
3) eOD-GT8 60mer is a nano-particle protein, it is found that this elicit immune response where above two proteins could not, it help in stimulation and then production of precursors required to produce antibodies against HIV.

eOD-GT8 60me NanoParticle

Director of National Institute of Health United States, Dr. Francis Collins have expressed his hope for success for these strategy over his blog.

Referances: 

Drug definition 

http://bvwaghmare.blogspot.in/2011/08/hiv-vaccine-research-b-cells-and-be.html

http://www.scripps.edu/news/press/2015/20150618aidsvaccine.html

http://directorsblog.nih.gov/2015/06/30/vaccine-research-new-tactics-for-tackling-hiv/#more-4837

http://www.nih.gov/news-events/nih-research-matters/hiv-vaccine-progress-animal-studies

Broadly Neutralizing HIV antibodies for passive immunization


Pharma Times 

B V Waghmare (2015). HIV Vaccine heading toward success. Combination of HIV neutralizing antibodies and Nanoparticle protien eOD-GT8 60mer are good hope for getting a effective anti HIV vaccine. http://bvwaghmare.blogspot.com

How to reduce cholesterol medicines for increased cholesterol

How to reduce cholesterol? Why medicines for cholesterol must be taken?
Which medicines are given to reduce cholesterol?
Higher level of cholesterol in body is very dangerous as it may block coronary arteries and may cause heart failure, cholesterol tend to form fatty plaques in veins and arteries, which when dislodged may occlude blood flow, if the artery that get occlusion is one that supply blood to brain in is very serious situation it can cause stroke, by virtue of occlusion of blood flow to brain.
Therefore it is must that one should not discontinue cholesterol reducing medicines without consultation of a doctor who is giving treatment for your increased cholesterol.
Cholesterol can be reduced by changing following things
A) Exercise combined with controlled diet:
1) Perform everyday physical activity or exercise that gives workout to your leg and thigh muscles and abdomen and arms. Morning breakfast with no or very low fat, butter should be avoided in breakfast, a breakfast containing lots fruits are found to reduce cholesterol and also gives very healthy body.

2) Afternoon meal and dinner should contain low fat, meat can be avoided if you require to eat a high protein diet, eat egg white portion only, avoid eating egg yolk consist of 1090 mg of cholesterol which is almost 360% of total requirement of cholesterol of from a single diet. Hence avoid eating egg yolk.
3) If you can avoid heavy dinner, just have few items just enough to give your health support.
4) Avoid eating late in night after 9:30 PM one should not eat heavy dinner, after 11:00 pm one should avoid dinner, and just have a glassful of hot milk.

Diet control is very important factor for reducing cholesterol, even though if cholesterol is keeping on high it is because of major change in metabolism of your body, it can be because of liver disease or disease that affects liver.

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Following drugs are used to treat hypercholesterolemia:

Protein that protect from TB infection developing in to lung infection

Biomarker that will help predict if a person will develop fetal lung disease associated with TB infection and can be used to treat Mycobacterium tuberculosis infection.

Every individual who encounter Mycobacterium tuberculosis infection do not develop an active form of TB, such individuals may test positive for Mycobacterium tuberculosis infection or antibody test.

A protein interleukin-32 is found in such individuals which protect them from developing TB infection into an active form of TB or fetal lung disease. Interleukin-32 help immune cells of body to kill Mycobacterium tuberculosis bacteria in presence of Vitamin D. Vitamin D is very important for protecting individual from developing active form of TB, in presence of Vitamin D protein interleukin-32 induce killing of Mycobacterium tuberculosis.

Presences of biomarker interleukin-32 in patients with latent TB can be used to predict if such patients will develop active form of TB or never. Synthetic Interleukin-32 can be used to develop pharmaceutical substance to treat TB patients with deficiency of interleukin-32 as well.

Source : http://www.uclahealth.org/main.cfm?xyzpdqabc=0&id=561&action=detail&ref=2549

Last updated: 07-Sep -2014

B V Waghmare (2014). Interlukin 32 biomarker that will predict relapse of tuberculosis infection and will be used in treatment of TB http://www.medicalwebsite.org/2014/09/protein-that-protect-from-tb-infection.html

HIV neutralising antibodies for passive immunization.

Advanced treatment of HIV infection with HIV neutralizing antibodies under development.

Anti retroviral drugs must not be discontinued so as to keep HIV viral load under control to maintain quality of life, still many patients discontinue taking drugs for many reasons like anti retroviral drugs have their own set of side effects and complications, availability.
Now such patients have better option as scientists from National Institute of Health United States of America have developed broadly active antibodies against HIV, which are tested in patients who have discontinued their medicines and were able to lower viral loads, in laboratory study it is proven that new CD4 cells were not infected by HIV virus in presence of these antibodies incubated for sufficient time.
These antibodies are Broadly neutralizing antibodies (bNAbs) which are called as PGT121, VRC01 and VRC03. These antibodies can be used for immunization for patients and healthcare personals at high risk. Combination of these antibodies along with HAART will help in reducing drug load and their side effects after prolonged use.

Source: http://www.niaid.nih.gov/news/newsreleases/2010/Pages/HIVantibodies.aspx

Last updated: 02-Sep-2014

Authored By : B V Waghmare

Immunotoxin destroys HIV cells novel approach in antiretroviral therapy

New class of antiretroviral drug being developed that destroys HIV infected human cells hidden deep inside tissues. Bacterial toxin which can eliminate tissue cells responsible for proliferation of HIV.

If you refer this page you will come to know that there are drugs available to treat HIV virus infection by attacking almost at all stages of infection of HIV (mode of action) except one point, that is destruction of HIV carrying human cells, there is no drug available which can find out HIV infected tissue cells and destroy them. Getting such drug would be a great breakthrough towards complete removal of HIV from human body.

A first step towards development of this novel class of antiretroviral drug is made by Dr. Edward A. Berger of (National Institute of Health) NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and Dr. Ira Pastan of NIH’s National Cancer Institute (NCI). To understand how this drug will work it is important to understand how HIV virus infects and multiply.

During infection process HIV virus first attaches to a Human CD4 cell and inject its RNA in to human CD4 cell; HIV RNA is converted in to DNA strand which is capable of transcribing HIV proteins essential for multiplication of HIV. This DNA get permanently attached to human DNA of human CD4 cell, and convert this human cell in to a HIV virus factory.

Therefore even though there are drugs designed to kill HIV virus at all stages, these HIV producing human cells are alive inside human body hidden in various tissues, which becomes active as soon as antiretroviral drug therapy is stopped. Therefore to eliminate HIV DNA carrying human cells is equally important to achieve complete removal of HIV virus from human body.

Cytotoxic HIV-specific immunotherapy is found to destroy human cells responsible for reproduction of HIV in is a toxin derived from bacteria and is known as immunotoxin 3B3-PE38.
This toxin was found to be effective in reducing the HIV viral load in humanized rat model. It was found that dose of immunotoxin along with antiretroviral drug therapy (ART) was successful in reduction of HIV loaded or HIV DNA carrying CD4+ T cells, macrophages and thymocytes.


Source:

Pharma Times 
http://www.ncbi.nlm.nih.gov/pubmed/24415939

http://www.nih.gov/researchmatters/january2014/01272014HIV.htm


Authored by : B.V. Waghmare

Last Updated : 28-Jan-2014

B V Waghmare (2014). Drug that destroy HIV carrying lymphocytes; will result in complete treatment that will not require to taking antiretroviral drugs through out life. http://bvwaghmare.blogspot.com

Dolutegravir The Second drug in the class of HIV integrase inhibitors

Second drug in the class of HIV integrase strand transfer inhibitors approved by US FDA to treat HIV infection

Until 13-Aug-2013 there was only one drug Raltegravir available under the class of HIV integrase strand transfer inhibitors, on 13-Aug-2013 US FDA approved one more drug Tivicay (dolutegravir), HIV integrase strand transfer inhibitor to treat HIV infection. It is found to be effective in patients which develop resistance to earlier available drug Raltegravir and for patients who have not yet received any HIV drug therapy.

HIV infection is critical to treat because it causes integration of HIV viral gene in the form of provirus DNA in to human DNA , HIV forms its DNA through a mechanism of reverse transcription from the viral RNA. Thus using metabolic activities of a normal human cell for its (HIV) reproduction
In-order to control the viral load, drugs which inhibits the almost all stages of infection are used. This is the base for combination therapy.

Information on Tivicay (dolutegravir):

Drug Tivicay (dolutegravir) belongs to HIV integrase Inhibitor. Drug Tivicay (dolutegravir) is approved by US FDA under fast track approval process for drugs, its efficacy and safety was evaluated in clinical trial conducted on 2,539 patients, Tivicay (dolutegravir) was given along with Atripla, a fixed dose combination drug which contain efavirenz, emtricitabine and tenofovir, and results were found satisfactory in reducing HIV viral count and increasing CD4 counts in participants taking Tivicay (dolutegravir), it showed satisfactory results in reducing viral load, patient aged 12 year with at least 40 kg who has not taken any anti retroviral drug therapy ( Treatment Nave ) were also shown reduction in viral count.

Drug Drug Tivicay (dolutegravir) is also been studied for use along with Abacavir and Lamivudine, in a new new fixed dose combination for its effectiveness and safety in reducing HIV viral count.

Source : http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm364744.htm


Authored by : B.V.Waghmare

Last Updated : 22-Aug-2013

Antiretroviral drugs available to treat HIV infection

Details of Antiretroviral drugs. 
1) Nucleoside Reverse Transcriptase Inhibitors (NRTIs) : In this class there are about thirteen drugs available.
2) Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs) : In this category Five drugs are available
3) Protease Inhibitors (PIs) : In this category 10 Drugs are available.

4) Fusion Inhibitors : One drug is available

5) Entry Inhibitors - CCR5 co-receptor antagonist: One drug is available

6) HIV integrase strand transfer inhibitors : Two drugs are available.


Antiretroviral drugs used in the treatment of HIV infection

Following is the list of drugs used in the treatment of HIV Infection

A) Multi-class Combination Drugs.

1) Efavirenz, Emtricitabine and Tenofovir disoproxil fumarate
2) Emtricitabine, Rilpivirine, and Tenofovir disoproxil fumarate
3) Elvitegravir, Cobicistat, Emtricitabine, Tenofovir disoproxil fumarate

B) Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

1) Lamivudine and Zidovudine
2) Emtricitabine, FTC
3) Lamivudine, 3TC
4) Abacavir and Lamivudine
5) Zalcitabine, Dideoxycytidine, ddC
6) Zidovudine, Azidothymidine, AZT, ZDV
7) Abacavir, Zidovudine, and Lamivudine
8) Tenofovir disoproxil fumarate and Emtricitabine
9) Enteric coated didanosine, ddI EC
10) Didanosine, dideoxyinosine, ddI
11) Tenofovir disoproxil fumarate, TDF
12) Stavudine, d4T
13) Abacavir sulfate, ABC


C) Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs)
1) Rilpivirine
2) Etravirine
3) Delavirdine, DLV
4) Efavirenz, EFV
5) Nevirapine, NVP



D) Protease Inhibitors (PIs)
1) Amprenavir, APV
2) Tipranavir, TPV
3) Indinavir, IDV,
4) Saquinavir (no longer marketed)
5) Lopinavir and ritonavir, LPV/RTV
6) Fosamprenavir Calcium, FOS-APV
7) Ritonavir, RTV
8) Darunavir
9) Atazanavir sulfate, ATV
10) Nelfinavir mesylate, NFV


E) Fusion Inhibitors
1) Enfuvirtide, T-20

F) Entry Inhibitors - CCR5 co-receptor antagonist
1) Maraviroc
G) HIV integrase strand transfer inhibitors
1) Raltegravir
2) Dolutegravir

Source :
http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/HIVandAIDSActivities/ucm118915.htm


Authored by : B.V.Waghmare

Last Updated : 22-Aug-2013

New Drug for Non Infectious Diarrhea Associated with antiretroviral drug treatment in HIV infection

Second botanical drug approved by US FDA for symptomatic relief from diarrhea associated with HIV infection and its drug treatment.


Symptomatic relief form diarrhea incase HIV infection, is very important for continuation of antiretroviral drug therapy, as antiretroviral drug therapy itself can cause diarrhea , and it is one of reason why many tend to stop HIV drugs just to get relief from symptoms of diarrhea.

US FDA has approved new drug Fulyzaq (crofelemer) for symptomatic relief from non-infectious diarrhea in adult patients on antiretroviral drug therapy. Fulyzaq (crofelemer) is a novel drug which is second most FDA approved herbal drug (drug from botanical origin) for symptomatic relief from diarrhea associated with HIV infection.

Inforation about Fulyzaq (crofelemer) :

Fulyzaq crofelemer is derived from latex of Croton lechleri Müll, and it is an oligomer , consisting subunits of , (+)-catechin, (-)-epicatechin, (+)-gallocatechin, and (-)-epigallocatechin linked to each other.

Mode of action :
Excessive water secretion in bowel causes diarrhea, it is because of excessive secretion of sodium ions and other electrolytes secretion in bowel, as a result patient suffer consistent watery bowel movements.
Drug crofelemer has unique property of blocking secretion of chlorine and calcium in to GIT and which reduce secretion of sodium and other electrolytes in bowel resulting in less amount of water secretion inside GIT and to protection from symptoms of diarrhea. Drug crofelemer blocks cyclic adenosine monophosphate (cAMP) stimulated “cystic fibrosis conductance regulator and calcium activated chloride channel” in GIT, the effect of drug is measured by presence of stool chloride ion. Before starting the drug Fulyzaq (crofelemer) it should be confirmed by test that diarrhea is non-infectious (not caused by bacterial, fungal or viral infection in GIT).

Diarrhea lasting for many days is one of symptoms of AIDS. Opportunistic infections and drug or antibiotics used to treat HIV infection and infections associated with HIV are responsible for causing diarrhea, sometimes drug resistance caused by drugs are responsible for growth of resistant Clostridium difficile infection which is one of cause for diarrhea related to HIV infection .

Sources :

http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202292s000lbl.pdf

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm333701.htm

Authored by : B V Waghmare

Last updated: 13-Jan-2013

3D Structure of an intermediate protein in infection process of HIV virus to CD4 cell reveled

New intermediate protein which facilitate attachment of HIV over CD4 and its 3D structure reveled. 

An intermediate temporary protein found in the process of infection of HIV virus to CD4 cell, this protein can be used in the development of vaccine against HIV. This temporary protein is occurs just before the attachment of HIV virus to CD4 cell.

The finding of this intermediate protein is very important for further development of antiretroviral drugs and vaccines; this can be very successful target for developing antiretroviral drug of category attachment inhibitors, and for further developments of neutralizing antibodies against HIV, and HIV vaccine as well.

The process of infection of HIV to CD4 cell is a complex one, it involves various steps, there are proteins over HIV core which first unbound and attach themselves over CD4 receptors over surface of lymphocytes followed by penetration and so on.

Developing a vaccine against HIV, which when given to human can stimulate development of antibody response in human body against incoming HIV infection through out human life, which will successfully protect human from incoming HIV virus infection is still a dream , which is yet to be achieved since the protein envelop of HIV keep on changing, Still there are certain points over HIV virus envelop which do not change but they are hindered by proteins preventing their presentation to immune system.

To overcome these hurdles in developing HIV vaccine a team from NIH's National Cancer Institute (NCI) led by Dr Dr. Sriram Subramaniam studied the structures of all proteins in the process of HIV infection, they used a technique known as cryo-electron microscopy where in the whole virus or purified viral proteins are frozen rapidly so that the Ice stays liquid like, in this technique proteins do not alter in there special orientation and do not get any damage still making available as rigid sample for observation this special frozen sample enable us to see the life like images of these proteins when observed under electron microscope.

Dr. Sriram Subramaniam and his team compared there dimensional structure of HIV virus envelop as well as protein which binds with CD4 receptor as well as to an antibody which mimics CD4 co- receptor, it was found that when HIV envelop is bound by any one of receptor the gycoprotien is transformed in to an activated state where 3 helical spring out in the center of HIV envelop, This activated protein is found between inactive position (which is not bound) and the immediate next structure of HIV Envelop, which occurs just after fusion.

Dr. Sriram Subramaniam and his team also studied portion of HIV envelop which binds with HIV neutralizing antibody VRC01 which were recently discovered in Aug 2011 and are capable of neutralizing many HIV strains. With these findings we will have information of events and proteins facilitating infection of HIV, just prior to HIV attachment to cd4 receptor.


Source: http://www.nih.gov/researchmatters/july2012/07302012hiv.htm




Authored by : B V Waghmare

Last updated: 09-Aug-2012

Protein which can inhibit HIV virus attachment and entry in to new CD4 cells.

Protein derived from platelet is found to exhibit broad spectrum HIV inhibitory properties.

There are few sites over HIV virus which are unique and have great potential as targets for new drugs and HIV neutralizing antibodies, these sites so far are not explored as new targets for new antiretroviral drugs, now this research finding will certainly open doors for development of drugs and HIV neutralizing antibodies which will be able to stop progression of HIV infection and disease.

Scientists at National Institute of Allergy and Infectious Diseases (NIAID), ( NIH) have discovered a protein called as CXCL4 (PF-4) in blood samples of people infected with HIV , it was fund that this protein binds with HIV virus and it do not allow HIV virus to infect new lymphocyte or CD4 cell, as HIV virus attachment to new CD4 cell and penetration steps in the process of HIV virus infection are blocked by this protein CXCL4.

CXCL4 or (PF-4) protein is a chemokine, which are known to facilitate transformation of immunological cells in tissues. There are four chemokines , of which three chemokines were found by Dr. Lusso, Robert Gallo, M.D and his team, these chemokinines along with CXCL4 have capability to bind HIV virus and inhibit its progression.

CXCL4 bind with outer protein coat of HIV virus at a site which is very different than other sites on HIV virus where drugs and HIV antibodies bind, Dr. Lusso, Robert Gallo and his team is working with scientists at NIAID Vaccine Research Center for identifying and locating structure of this site by atomic level crystallography. This site may be very helpful in further developing a drug and HIV vaccine which specifically target this site.

CXCL4 protein has capability to bind on variety strains of HIV virus, CXCL4 protein is made by platelet.
Dr Lusso and his team is now engaged in finding further how this finding on chemokines and CXCL4 can be used to develop new options for HIV neutralizing antibodies or vaccine or an antiretroviral drug which can target specifically at binding site of CXCL4 over HIV.


Source: http://www.niaid.nih.gov/news/newsreleases/2012/Pages/CXCL4.aspx




Authored by : B V Waghmare


Last updated: 20-6-2012

HIV vaccine reasearch heading towards success

Antibodies of class Immunoglobulin G (Ig G ) increase protection in HIV vaccine trail, provide a clue for future development of HIV vaccine .

Any vaccines work by inducing production of antibodies against any infective microorganism in our body Incase of HIV, antibodies produced are not able to stop or kill HIV virus as HIV virus proteins keep on changing due to high rate of mutation and keep on presenting variations so that induced antibodies incase of HIV do not confer complete protection against HIV.

Now in a new research conducted by researchers led by Dr. Barton F. Haynes from Duke University, it is found that higher concentration of particular antibodies belonging to class Immunoglobulin G (Ig G ) have imparted increased protection in individuals who had participated in a clinical research on HIV vaccine conducted at Thailand in 2009, about 1600 volunteers participated in clinical trial on HIV vaccine.

About 31 % population which received an experimental HIV vaccine had lower chance of getting HIV infection compared to individuals given only placebo control group.
Dr. Barton F. Haynes of Duke University and his team analyzed serum samples from 246 vaccinated volunteers and it was found that there is higher concentration of Ig G concentration in individuals which showed increased protection, and there was high concentration of Ig A antibodies in volunteers which were not shown protection.

Ig G antibodies attach to variable regions V1 V2 on gp120 protein which help HIV virus in the process of attachment to host cell.

Increase concentration of Ig A antibodies in individuals which did not show any protection might be due to hampering of activity of Ig G antibodies, by attaching at C1, first constant region.
NIAID Director Dr. Anthony S. Fauci has expressed hopes for developing a successful vaccine against HIV in near future by using present findings.


Source:  http://www.nih.gov/researchmatters/april2012/04162012hiv.htm
===============================================================

Authored by :  B V Waghmare

Last updated: 20-4-2012

Anti retroviral drugs of class protease inhibitors drugs and increased blood cholesterol level.

Antiretroviral drugs belonging to class protease inhibitors are known to cause increase in cholesterol level in patients taking protease inhibitors drugs. Anti retroviral protease inhibitors drugs which act by inhibiting enzyme protease , this enzyme helps HIV virus in building its protein by breaking higher proteins in to smaller on, and then make use of these smaller one for building HIV and viral envelop and thus help in reproduction of HIV virus.

Every drug do not specifically act on a particular system, but they do have some varied degree of action on other metabolic and biochemical systems and cycles, antiretroviral drug belonging to category protease inhibitors cause increase in cholesterol, in a broader term this class of drug may cause hypertriglyceridemia, hypercholesterolemia and the increased cholesterol level in patients and subject them to high risk of developing atherosclerosis, by increasing the level atherogenic lipoproteins and endothelial dysfunction which increase the risk of atherosclerosis and heart disease.

Drug Norvir, is known to cause more hyperlipidemia compared to other protease inhibitor drugs . Also a non protease drug Sustiva is also known to increase blood lipid levels. Other underlying factors like smoking , alcohol consumption , and low physical activity , which affect lipid metabolism and are responsible for increased blood cholesterol level must be considered , there is great risk of developing hyperlipidemia with those underlying factors.Patient are advised to quite smoking and do some physical exercise regularly, must avoid alcohol.

What is done when a patient develop hyperlipidemia :
Hyperlipidemia associated with protease inhibitors is a reversible type which means it ceases if changes are made in antiretroviral drugs to treat hyperlipidemia, doctor decide up on consideration of the risk of hyperlipidemia compared to viral count and patients health, hyperlipidemia is also managed with exercise and altering the food to low fat diet.

Incase of sever conditions following drugs which lower blood cholesterol are given
Statins : Lipitor (atorvastatin) and Pravachol (pravastatin).
Fibrates: Lopid (gemfibrozil) and Tricor (fenofibrate)

All above drugs have serious side effects in high dose and long term , for example, drug belonging to group statins are known to cause rhabdomyolysis and drug belonging to group Fibrates are known to increase risk of developing gall stone.

Source:

http://www.jci.org/articles/view/16261#B5

http://www.aidsinfo.nih.gov/contentfiles/Hyperlipidemia_FS_en.pdf

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Authored by :  B V Waghmare

Last updated: 06-Sep-2011