A brief insight on ACE receptors role in COVID-19

A brief insight on ACE receptors role in COVID-19

With the novel coronavirus, COVID-19 is spreading across the world and the fact that no drug or treatment has been found against it is creating fear among people. Coronavirus is a large family of enveloped, single-stranded RNA that infects mainly mammals including humans. In humans, coronavirus causes mild to severe respiratory illness. These viruses exhibit strong virulence and are highly contagious. While a person infected, produces mild symptoms, certain individuals respond severely, sometimes leading to death. 

The SARS pandemic, back in 2002 is known to belong to the same family of viruses as COVID-19. According to WHO, SARS rapidly spread through 29 countries, with 8096 confirmed cases, but the current pandemic has surpassed all numbers by infecting over millions of people across the world. Today, it is due to SARS that has resulted in a coordinated effort to develop treatments targeting the virus or host cell components responsible for viral replication.

The deadly virus, COVID-19 enters the human body and binds to the target cells through angiotensin-converting enzyme 2 (ACE2) which is mainly expressed in endothelial cells and Leydig cells. ACE-2, a transmembrane metallo carboxypeptidase, is an enzyme which for years has been important for the treatment of hypertension. With further Polymerase Chain Reaction (PCR) analysis it was determined that the ACE-2 receptor is also present in the lung and gastrointestinal tract, tissues harboring COVID-19. 

Inhibiting ACE2 receptor blocks COVID-19 entry:

ACE-2 belonging to the family of ACE receptors, plays a key role in the Renin-Angiotensin System (RAS) and in the treatment of hypertension. ACE2 is known to degrade angiotensin II and thereby, negatively regulating RAS. Recently experts have revealed that the COVID-19 virus uses ACE-2 receptors as their entry in HeLa cells. Additionally, it was found that by using anti- ACE-2 antibodies in other mammals like monkeys, it was seen that there was an entry blockage of pseudotypes expressing the COVID-19 virus. 

For the virus to enter the host cell, its spike glycoprotein (S) needs to be cleaved at 2 sites, termed S protein primming so the viral and host cells membrane can fuse. A serine protease TMPRSS2 is essential for cleaving the S protein. It was found by treating Calu-3 human lung cell line with a serine inhibitor- camostat mesylate the entry of the COVID-19 virus was partially blocked. Angiotensin-converting enzyme (ACE) inhibitors is also found to play a role in preventing the formation of angiotensin II. ACE multifaceted functions include treating heart failure, controlling high blood pressure, and preventing kidney failure in diabetic patients. 

Existing concerns about ACE inhibitors:

Though ACE inhibitors might seem like a promising solution for COVID-19, there are certain concerns regarding the increased susceptibility to COVID-19. These are considered based on the fact that ACE inhibitors are also used in treating millions of people with hypertension, heart, and kidney disease. When administered with inhibitors, diabetes and hypertension patients were observed to have an increase in ACE2, which in turn would facilitate infection with COVID-19. It is hence hypothesized that treating diabetic and hypertension patients with ACE inhibitors might make them more susceptible to COVID-19. 

Furthermore, several studies have reported that long term usage of ACE inhibitors can modify the adaptive immune response, which is a key and much-needed defense against any infection. These particular effects must be taken into noticed and investigated further in context to COVID-19. 

Road to COVID-19 therapies:

These findings could greatly impact the efforts being taken in developing treatments for the current pandemic. For instance, TMPRSS2 inhibitors can be potentially used to prevent virus entry into the host cells. Though there are certain drawbacks in using ACE inhibitors, there is a lack of scientific evidence and clinical data to support the discontinuing of ACE inhibitors in COVID-19 patients with existing hypertension and diabetes. The proof that reduction in mortality due to ACE inhibitors and the beneficial effects outweigh the theoretical risks. 

Our interpretation of this hypothesis should not lead to changing drugs for patients with diabetes or hypertension, without consulting an expert physician. Though it’s of utmost urgency for the scientific community to come up with some solution for this deadly virus, further research and clinical trials need to be performed before any of the said theory can become a reality. 

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Mutant Polio Virus from Vaccine more infectious than the wild type

Mutant Poliovirus from vaccine more infectious than the wild type

How it all began?

Back in the 20th century, there were many more diseases that worried parents then Polio did. Polio struck during summer, making its way through towns, every few years. Most people were reported to recover quickly, though some suffered temporary or permanent damage leading to paralyzation and even worse, death. With many polio survivors disabled for life, it was a constant reminder to the society the toll it took on young lives. Polio reached the level of epidemic proportions back in the 1900s affecting the infant and young kids, where the infant’s immune system is still aided by maternal antibodies could not fight the virus. 

Polio is caused by a family of viruses belonging to the Enterovirus genus. These viruses are highly contagious usually spreading through contact with people either by oral or nasal secretions, or by contacting a contaminated area. The virus enters the mouth and is found to multiply by the time it reaches the digestive tract, where it continues to multiply. In cases of paralytic polio, the virus makes its way from the digestive tract to the bloodstream attacking nerve cells. 

Development of vaccines to eradicate polio: 

A vaccine is made from a very small amount of wither weak or dead germs that cause the disease, for example-poliovirus. When administered, the vaccine introduces the said virus into the body to trigger an immune response, causing it to recognize and combat the actual disease if encountered in the future. 

 The antibodies specific to the poliovirus was first discovered in 1910. Using immunologic techniques, it was in 1931 different serotypes of the poliovirus were identified. By identifying that the virus can be grown in large amounts using tissue culture, it was just a short time before the first inactivated polio vaccine (IPV) was developed. With human trials being deemed a success, the number of polio cases drastically dropped over the years. Later an improved version of the vaccine using live attenuated virus was developed, which could be administered orally, known as oral poliovirus vaccine (OPV). Soon it became the predominant go-to vaccine for developing countries all over the world, declining the number of cases drastically till a new problem raised recently. 

Vaccine-derived poliovirus:

Over the past few years, more than 10 billion doses of OPV have been administered to millions of children worldwide, preventing more than 10 million cases during that period, bringing down the number of cases drastically. 

So far in the year 2017, only as many as 6 “wild” polio cases were detected worldwide. By wild it means that the number of cases affected by polio “wild type” strain found naturally in the environment. Recently, new cases have been reported of children paralyzed by a vaccine-derived poliovirus. Around nine new cases were identified in countries- Nigeria, the Democratic Republic of the Congo, Central African Republic, and Angola last November, along with Afghanistan and Pakistan. The WHO reported that as long as a single child is infected, all the other children are at risk. 

In developing countries, the oral vaccine is used profusely among all children due to its low cost and accessibility. The vaccine-associated paralytic polio is caused by a strain of poliovirus which was previously termed wild type. The onset was found to be caused by a type 2 virus contained in the oral vaccine. Type 2 virus was a wild type virus eradicated years ago, but in rare cases can mutate into a form that can breach the vaccine protection. 

Erradication possible:

With the COVID-19 outbreak, the WHO has also additionally undertaken the goal of eradicating the new mutant poliovirus before its too late. The role model here is smallpox, which was completely wiped out thanks to a consistent vaccination strategy. The same applies to polio. Similar to smallpox, the polio vaccine also offers impeccable protection, though not applicable to virus mutants. Reports state that the latest mutant outbreak is due to the low vaccination rates. The rise in vaccine-derived polio cases is due to the mutant form of the disease affecting the non-vaccinated children through contaminated matter. 

The coverage of vaccination and hygiene measures must be extended so that the new mutant can no longer continue to survive, the same way the previous polio epidemic in Congo was eradicated. Though the current vaccines appear to be good enough to be effective, the new pathogen is nonetheless a warning. The need for new protectant vaccines is more important now than ever. It is only this way there is a chance of permanently wiping out polio. 

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