Vaccine INO-4800 | Social distancing | Vaccine for COVID-19 | BioNTech | Recombinant protein | Moderna’s mRNA 1273 | ChAdox1-ncov 19 | Coronavirus treatment | Clinical trial | USA | UK | China

Chinese biotech firm had proved positive results in an animal model and it is the first vaccine development that was tested in rhesus macaques. Sinovac  Biotech, a biotech firm in china gave 2 different doses of vaccine to 8 macaques and after 4 weeks of observation, none of them had the infection. The human trial began and during the animal testing, the best outcome came from the best dose. This company is a well-experienced vaccine maker and they have previously worked with diseases such as hepatitis A and B  and H5N1 influenza. The human clinical trial consist of 144 volunteers, to whom different doses of the vaccine were tested.

6 vaccines have entered the human trial and 77 more are under development. The major developer uses genetic engineering and the other 4 used old inactivation methods of developing.

Cansino's Ad5-nCov  completed Phase I trial

Cansino's Ad5-nCov  Vaccine candidate successfully completed the phase 1 human trial. This organization started enrolling volunteers for the phase 2 trial. It is a DNA based vaccine that used a recombinant protein approach for development. This firm has also already started working for the phase 2 trial of Ebola vaccine (Adenovirus) Ad5-EBOV. This company is planning to enroll 500 patients in Wuhan. 250 – phase I middle dose, 125-low dose, and 125 placebo injection. These are the number of people involved in dosage optimization.

 Johnson& Johnson

They have not yet started any human trail but they have been working with vaccine development with the same vector and signed a huge deal with HHS/BARDA. The phase I trial will not begin until September.  The adenovirus vector needs a correct approach to grow a more viral vector.

Insect cells  to develop recombinant proteins

The big giant Sanofi used their approach of developing vaccine by using insect cells to recombinant antigen proteins. This approach has been already approved for a flu vaccine. This approach is to be combined with GSK’s adjuvant (immune boosters).

 Vaccine INO-4800

Inovio-4800 is a DNA vaccine that is similar to that of the mRNA vaccine. This firm has been working on this for several years and other diseases such as MERS/SARS. They started with 40 volunteers in the US and another challenge is that they are developing a vaccine delivery devices for injecting through the skin.

mRNA based vaccine

BioNTech has a deal with Fudan's work on coronavirus vaccine in china. They have signed up a deal with Pfizer. German regulatory authorities have approved to begin Phase I and II trails. This trail is to enroll 200 volunteers for dosage evaluation.

ChAdox1-ncov 19

Oxford University has completed its phase I trial which had no safety problem and they are, to begin with, 510 volunteers for phase II trial. It is an Adenovirus vector from a chimpanzee that has a similar concept of the Cansino vaccine.

Moderna’s mRNA 1273

This US-based firm is expertise in mRNA therapies. They are in collaboration with NIH. The study will deal with 45 patients phase I trial in Seattle  and larger group at Emory which will have doses of 25,100,250 mg of mRNA in various age groups.

Summary:

• Inactivated virus vaccine- Wuhan institute for Biological products,  Sinovac’s PicoVacc
• mRNA based vaccine- BioNTech/Pfizer, Moderna mRNA-1273
• Adenovirus vaccine- Cansino's Ad5-nCov  , Johnson& Johnson,  Oxford Vaccine(ChAdOx1-nCov 19)
• DNA Vaccine- Inovio’s INO-4800
• Recombinant protein- Sanofi/GSK

ULTOMIRIS | SUPERCOMPUTER | US-FDA | COVID-19 KIT | DATA SCIENCE | GAMERS

Home Test for COVID-19

LabCorp, a diagnostic maker for COVID-19 will provide first access to health care workers to take the COVID-19 test personally, who are eligible to swab the fluid sample from the nose but they need to send the sample to the testing laboratory. The US-FDA has issued authorization for home testing of the COVID-19 kit. The person will need to swirl a cotton swab inside the nostril. Self swabbing will be more accurate according to the analysis done by the United Health group.

ULTOMIRIS to enter Phase 3 clinical trial

ULTOMIRIS is also known as Ravulizumab which is a type of monoclonal antibody that is used to treat paroxysmal nocturnal hemoglobinuria(PNH) in adults. PNH is a genetic disorder in which defective  RBCs break down at the premature stage and leaks in the blood.

Alexion Pharmaceuticals has announced to initiate a phase 3 trial of  Ravulizumab that comprises 270 adults with severe COVID-19 and severe pneumonia or acute respiratory distress syndrome. This phase is to evaluate the safety and efficacy of the drug and the primary goal is to survive on day 29. The secondary will be the need for ventilators, ICU, oxygenation.

The action of a plan:

Weight-based dosing  will be followed on day 1.

           

Dose (mg)	Weight (Kg)
2400	40-60
2700	60-100
3000	≥ 100

           

            

Days 5,10,15 will be also weight-based,  patients weighing 40-60kg will receive 600mg of  ULTOMIRIS, and patients with more than  60 kg will receive 900 mg of ULTOMIRIS. The treatment follows up will be for 4 weeks and followed by safety monitoring.

 Folding@Home

PC owners ad gamers have created the world’s fastest supercomputer to combat coronaviruses. Volunteers will have to run the app that uses their PC’s processing power to help the researchers for the finding of coronavirus vaccine. The name of the application is Folding@Home,  this uses resources from 1000 computers around the globe to work through large sets of numbers and complicated problems. This outperformed the 500 fastest supercomputers in the world combined. Researchers are using this supercomputing brain.

Mechanism of work: This app’s processing power will be used to understand how the spikes of coronavirus enter the human cell. Similarly, many studies are ongoing to detect how the spike of the SARS-COV2 virus attaches itself to human cells, infects the body, and takes hold of it. This app will develop future treatments through simulations of how spike proteins work. Single PC might succeed in developing a part of the process. Around 700,000 new users have joined Folding@ Home and around 30,000 people can run the app simultaneously.

It has reached 2.4 exaFLOps of processing power. Summit, it’s the world's fastest supercomputer, belongs to the US department of energy. Summit can reach a peak performance of 187 petaFLOps that is equal to under 19% of an exaFLOP. This app splits up complex protein models into tiny tasks that are distributed to many users around the globe. This app allows PC owners to decide what percentage of their computer’s processing power can be used.

Auranofin | Exercise | Cytokines | Antioxidant | Pharmaceutical industries | Generics | COVID-19

Drug repurposing plays an important role in treating  COVID-19. Some of the positive results have been shown in patients. Any guess which drug it is, yes Auranofin is a chemical compound that contains gold particles and scientists are experimenting with gold particles to treat diseases such as HIV, cancer, neurogenerative disorders, and bacterial infections. Auranofin is effective in COVID-19. This drug was approved by the FDA to treat rheumatoid arthritis. Many researchers say that the repurposing of a drug is the best way to treat COVID-19.  SARS-CoV-2 needs host cell proteins to replicate them. Some effective drugs interfere with this replication process. Based on the Cell-line studies,  the viral amount within the cells dropped by 95% after 48 hrs of treatment. There is a reduction of inflammation induced by the coronavirus. Auranofin reduces the expression of cytokines, that draws attention by immune cells at the injection site. This team plans to study the effects of drugs on animal models. During the cytokine storm, the immune response gets out of control. As it kills healthy cells and may lead to organ failure. This drug could inhibit the replication of the novel coronavirus and mitigate the infection by reducing the lung associated damage. Lung damage caused by COVID-19 often leads to severe respiratory distress.

Exercise will protect from COVID-19 complications, Yes based on the research conducted by the University of Virginia, they found out that the risk of acute respiratory distress syndrome can be reduced.  Extracellular superoxide dismutase (EcSOD) is an antioxidant that helps in preventing diseases, mostly EcSOD is secreted in the muscles naturally that binds to vital organs. Their production is increased by cardiovascular exercises. Regular exercise has been medicine for a decade.

Will India become a bio-medical hub after the COVID-19 crisis? the answer is yes many start-up firms have started from ideas to proof of concept. The stock market of pharmaceutical industries has been increased for the past few days. But if the government supports more in their annual budget we will have a good health care system and we can rise in the global economy. Make in India concept will surely help any organization in the future. We can proudly say Indian pharmaceutical companies are dominant in generic drug manufacturing. Around 90% of drugs in the U.S are generic and more than one third are manufactured in India. This will have more impact on the future.

Will ebola emerge again? | Viruses | COVID-19 | Vaccine trial | Blood brain barrier | Drugs| Africa | congo| vaccine for ebola

Why viruses and bacteria can’t enter our brains?

Blood-Brain Barrier(BBB), it is a protective layer covered by our brain. It is a barrier that is found between blood vessels and the brain. It doesn’t allow bacteria and viruses to invade inside the brain. BBB is a selectively permeable barrier, controls what should go inside the brain and what shouldn’t. Molecules such as glucose, oxygen, and water can pass through BBB. Blood vessels in the brain have specialized endothelial cells that are tightly packed and form a tight junction. Small molecules enter into this tight junction. BBB found to be a challenge for drug delivery.

Trojan Horse approach is a technique that is used for drug passage, the drugs are fused to a molecule that can pass the barrier. It involves coupling therapeutics with antibodies, that bind to the surface receptor on the blood barrier. After this, receptor activation occurs and enter into the cells and pass the layer and enter into the brain.

Engineered viruses also used for penetrating the brain that delivers drug therapeutics into the brain cells.

Ebola is back again but where? Yes, it is in the Democratic Republic of Congo, an 11-year-old girl died due to ebola virus. Who is Ebola?, Ebola virus disease is a rare group of viruses that was first found in 1976  near the ebola river(Democratic Republic Congo) in the African continent. Researchers believe that virus may have come from non-human primates.

Transmission:  virus spreads through contact with the blood or body fluids, infected bats.

Treatment: currently no approved drug for Ebola treatment, but during the 2018 outbreak. Two antiviral drugs called Regeneron and mab114 was used in patients. 

Any Vaccine available: Ebola vaccine called rVSV-ZEBOV was approved by FDA on December 19, 2019. This Vaccine is found to be safe against Zaire a species of ebola. Another vaccine is been under development that needs two vaccine components ( ZEBOV and MVA BN-Filo)  that require two doses that are initial and booster dose that is 56 days later.

70 vaccine trials are going on for COVID-19, in that 3  being tested in humans. Based on the report of Oxford University, the vaccine could be ready by September of this year. If the officials push for the emergency crisis. Once the trials work in humans, the researchers expect that vaccine development would take between 12 to 18 months.

Disinfectants | Aarogya Setu app | Obesity | Amazon tribe | COVID-19 | Plasma therapy

Amazon tribe tested positive for COVID-19

Brazil officials confirmed the 1^st positive case of COVID-19 in the Amazon tribe. Yes, it is Yanomami tribe which has 38,000 people in South America. It is 15^th the year-old boy got infected with COVID-19, who had no contact with the outside world. As per today, brazil has confirmed at least eight corona cases among their population.

Research conducted by Smithsonian’s National Zoo and Conservation Biology Institute found out that 6 new coronaviruses in bats in Myanmar. These viruses are been identified for the first time across the globe. The authors predict that these novel coronaviruses will not have any impact on humans health and added that these novel coronaviruses are not linked with SARS-COV-1, MERS or COVID-19.

Based on the patient's data, researchers found out that obesity is a major risk for COVID-19 infection. This study was based on France patient’s data, and say that viruses can target young people particularly obese young people. 88% of patients who suffered only severe flu-like symptoms. The young people's mortality rate was 2% but rose to 14% who are more fragile. This can lead to diabetes and cardiovascular disease that may increase COVID-19 infection.

Aarogya Setu app is an official COVID-19 app launched by the Indian Government. This app was developed by National Informatics Centre under the Ministry of Electronics and information. This enables the user to know more about the COVID-19.

How to prepare Disinfectants at home

Chlorine bleach is a well-known disinfectant which is costs less too. Special care must be taken for people with autoimmune diseases or cystic fibrosis.

The Centers for Disease Control (CDC) recommends using different dilutions of bleach and water.

Materials required:

• Plastic spray bottle or glass jar
• Measuring cup
• Cloth
• Gloves
• Household bleach
• Water

Procedure:

• Find an open space, as bleach releases fumes that are toxic. Make sure you wear protective equipment such as gloves and shoes
• Mix one cup of bleach(240 ml)  with 5 gallons of water(18.9 liters). This is to ensure a 1:10 ratio of preparing disinfectant.
• Transfer the bleach the solution into a plastic bottle or glass jar and then add water.
• Thus Disinfectant has been made at home.
  

Precautions: Never add these 3 chemical compounds such as Ammonia, Acidic compounds, and alcohol to bleach solution. Don’t expose to heat, sunlight, and evaporation.

Convalescent plasma therapy- what is it and how could it  be beneficial for COVID-19 infected people.

It is an adaptive immunity therapy that has been found to treat many infectious diseases over a century. This treatment was successfully used in  SARS, MERS and H1N1 pandemics. Now recently FDA has approved to treat severe-ill COVID patients using Convalescent plasma therapy.

SARS-COV-2 | Virus| Flu | Bio-safety | COVID-19 | Chickenpox | Mumps | Influenza

Biosafety cabinet- What it is and different types and how it can be used effectively?

Basically a biosafety cabinet is a micro-biosafety cabinet that is also called a biological safety cabinet, where it is mostly enclosed with ventilated laboratory workspace for pathogens.

The main use is to protect the people working with laboratory pathogens.  All exhaust air has HEPA filters(high-efficiency particulate air) that remove harmful viruses and bacteria. HEPA filters were commercialized in the 1950s.

It is similar to that of the laminar flow chamber, but this blows unfiltered air towards the user and considered to be safe for working with pathogenic agents.

Types of BSLs:

The U.S  Centers for Disease Control and Prevention classified  into four  types

BSL-1	BSL-2	BSL-3	BSL-4
This type of cabinet provides environmental and personal protection but fails to provide product protection. This type is used in case of working with non-causative microbes to humans. Eg: E.coli	This is suitable to work with pathogens that cause moderate harm to the environment and personal. An example includes the HIV virus, hepatitis A, B, C virus.	This type is used in serious pathogens to the environment that includes Mycobacterium tuberculosis, SARS coronavirus. All laboratory workers will be under medical surveillance and must wear personal protective equipment while inside the cabinet.	This is the highest level of safety cabinet. In this highly transmitted pathogens such as Ebola, Nipah, flavivirus work will be taking place. High safety and precautions measures will be taken inside this type of cabinet.

Currently, India has  3 BSL-4 laboratories they are

1. High-Security Animal Disease Laboratory(HSADL), Bhopal
2. Centre for Cellular and Molecular Biology(CCMB), Hyderabad
3. National Institute of Virology, Pune

The COVID-19 is an airborne virus. Let us see what is an airborne virus and different types of it.

Airborne virus: This a type of virus that can be transmitted via aerosols and people get infected.

Different types include

1. Measles:  This virus can stay up to 2 hours in the air and infected people can exhale around 5000 viral particles into an hour. This virus kills around 2,00,000 every year

2. Influenza: This virus is very small and it can stay at least an hour in the air. It is Influenza A that is responsible for Flu in humans. Around 500,000 deaths are due to the influenza virus every year across the globe.

3. SARS-COV-2:   COVID-19 can stay up to 3 hours actively in the air. It varies with different surfaces.

4. Chicken Pox: A herpes virus called Varicella zoster causes chickenpox, it can stay up to several hours in the air. This virus causes a rash that turns into blisters. It takes up to 2-3 weeks for a pox to appear.

5. Swine Flu: This flu is caused by the H1N1 virus that causes a respiratory infection in humans. The droplets spread about 3 feet and remain in the air up to 2 to 8 hours.

6. Mumps: It is caused by the Rubula virus. This virus spread through sneeze and cough. It mostly affects the salivary gland, due to swelling as a result of infection.

7. Rubella Virus: This virus spreads through close contact with an infected person. It causes slight fever, mild rash and swollen glands. Humans are the only host for the rubella virus.

Gilead Sciences | COVID-19 | Remdesivir | Favipiravir | Japan | UK

Drugs enter into Phase III  trials on COVID-19 patients. Any guess on which drug entered into this segment. Yes, it is Favipiravir and Remdesivir that entered into phase 3 of human trials. As this phase is more important for the approval from healthcare authorities. Phase III clinical trials involving around 3000 participants. Selected participants have the condition that the new drug is to treat. This is a phase to evaluate how the new drug works when compared to the existing drugs in the same condition. The developers of Favipiravir(Avigan) have increased the production of antiviral drugs when they announced the phase iii clinical trial to test the safety and efficacy of the drug against COVID-19.

Avigan is approved to manufacture and sell in japan as an influenza antiviral drug. It is manufactured by Fujifilm Toyama Chemical Co.Ltd.

Mechanism of action: Favipiravir selectively inhibits the RNA polymerase of the influenza virus, this polymerase enzyme is necessary for viral replication, once the virus enters into the human host.

How this could be beneficial in COVID-19?

Yes, COVID-19 uses the same principle to replicate and categorized into the same single-stranded RNA virus like influenza. Therefore Researchers believe that Avigan may be effective in treating COVID-19.

Note: Avigan could be used only if the novel or remerging influenza outbreak occurs, and available antiviral drugs are not effective enough.

Avigan’s production and distribution are controlled by Japan's Health, Labor, and Welfare Ministry. It has been distributed in the market in Japan or overseas. Fujifilm is planning to co-operate with domestic and overseas partners to accelerate the production of their antiviral drugs.

Gilead Sciences also announced that it has initiated two phases of III studies to test the safety and efficacy measure of Remdesivir in patients with moderate to severe COVID-19.

Note: These two studies were given Urgent Public Health Research (UPHR) status by UK health authorities.

Researchers say that Remdesivir is an investigational nucleotide analog. It showed broad-spectrum antiviral activity both in vitro and in animal models against different types of emerging viral pathogens. These phase III clinical trials will help to generate crucial data on  safety and efficacy of the drug. The selected locations for phaseIII trials are mostly in the hospital of the UK.

Containers | Drugs | Vaccine | Infections | COVID-19

Risks faced by dead bodies after natural disasters

Most of the microbes do not survive after the human the body dies, but in certain cases, there is a risk to the healthy people after the dead too (Cholera and hemorrhagic).

Healthcare workers who routinely handle these things may have a risk of getting Tuberculosis, Bloodborne viruses( Hepatitis B and C, HIV) and gastrointestinal infections (eg., cholera, E.coli, typhoid/paratyphoid fevers. In the case of gastrointestinal infections, workers may be directly transmitted from feces leaked from dead bodies. In the case of COVID-19, there is no such incidence of transmission after death, since it is a new disease. The main transmission in COVID-19 is through droplets.

Note: The family of the patient can view the dead body at the time of removal with standard precautions.

DNA vaccine enters into human clinical Trials 

This is the second vaccine that enters into human trials for COVID-19.

The U.S based Inovio pharmaceuticals enter into phase 1 human trial after showing prominent results in preclinical studies.

Mechanism of action: INO-4800 DNA vaccine works by injecting a genetically engineered plasmid that enters into the patient cells, that could produce desired and targeted antibodies and fight the infection. The availability of this vaccine in the market would take at least a year.

Note: DNA vaccine has not yet been approved across the globe in human use.

 New Antiviral drug enters into clinical stage

Researchers hope that a new drug called EIDD 2801 could help COVID-19 patients. This drug has been found to reduce lung damage in in-vitro studies. This research is under study by The University of North California.

EIDD-2801 is an orally available form of antiviral compound EIDD-1931. This can be taken as a pill and get absorbed to travel to the lungs. As per in-vitro study data, when this drug was given as treatment  12 or 24 hrs. EIDD-2801 has found to reduce weight and lung damage in mice. If this drug is found to treat COVID-19 in human trials. In future cases, it can also be used to study other pandemic viruses.

Shipping containers to be turned into hospitals for COVID-19 treatment

Since there is a lot of demand for Intensive care units, ship containers are to be converted into two-bed intensive care units. One such earliest design is called RUAGField Hospital, it uses a combination of standard ISO Shipping containers and expandable or foldable containers to build field hospitals. 

Another type of design called Cura ( Connected units for Respiratory Ailments), In this type they use previously used shipping containers to build pop-up shops and co-working spaces. These containers can be shipped to any locations by means of transport. So, this could be ready to support treating patients. Their team got the first prototype to manufacture in Turin, Italy. Italy has 12.5 critical care beds per 100,000 people, while Germany has 29.2 beds per 100,000 people. Whereas researchers estimated that the UK will need 200 beds per million people. 

Some Countries repurposed convention centers and filled with as many as beds as possible. There is a problem in this type, as an intense concentration of contaminated air in these field hospitals, and the second solution is prefabricated hospitals. These prefabricated hospitals have full mechanical ventilation, in addition to negative pressure systems.

Pharmaceutical industry | Drugs | Malaria | Face masks

Drug repurposing, what it is and how it would be beneficial to people. Some of the already approved drugs could be used for treating new diseases. Scientists across the globe are working for the treatment of COVID-19. Drugs used for the treatment of HIV, Arthritis, Malaria are under study.

1. Chloroquine- this has been used for the treatment of malaria in nearly a century.

It is a synthetic version of quinine that exist as natural compounds in the bark of cinchona trees.

Mechanism of action: It slowdowns the entry of virus into the cells, that slows the rate of replication

2. Hydroxychloroquine- it is closely related to chloroquine, it is considered as less toxic for malaria treatment. In some other cases, it can also be used to treat autoimmune diseases(lumps and rheumatoid arthritis). It is available in the market since 1950s.

Mechanism of action:  This works by disrupting the communication between cells in the immune system.

3. Kaletra- it is a combination of two antiviral drugs. Lopinavir and ritonavir used for HIV. This drug is widely available and undergone clinical trials.

Lopinavir- it prevents  viral enzymes from cutting   important proteins(that are key to HIVs reproduction), whereas Ritonavir helps in boosting of lopinavir concentration in cells.

Some study claimed that, no benefits to COVID-19 patients.

4.Remdesivir- This drug was developed to fight against Ebola, But failed to prove effective. But this showed positive results against MERS and SARS. The working of this drug in COVID-19 patients are unclear yet. But some studies showed that it blocks RNA replication during the reproductive stage of coronaviruses.

5.Losartan- it is a hypertension drug that reduces blood pressure by preventing angiotensin(hormone) from binding receptors on blood vessels

6.Favipiravir- It is a flu drug developed in Japan. It showed prominent results in cases of COVID-19. This drug has been used for the treatment of influenza in Japan. In march 2020, this drug has been approved for experimental treatment for COVID-19 patients.

7.Actemra- It is an immunosuppressive drug  that is used to quiet cytokine storms. It has been approved for the treatment of rheumatoid arthritis and juvenile rheumatoid arthritis. It works by blocking cell receptors that bind to interleukin 6. IL-6 is a cytokine that can trigger dangerous inflammatory cascades.

How Bats are not affected by COVID-19

Warning: Do not take those drugs without doctor's prescription.