Fighting coronavirus: a breakthrough on the molecular front
Following the World Health Organizationâs declaration of a pandemic on March 11th, countries around the world have buckled down for a fight unlike one we have ever seen before. As the pandemic rages on, the most important thing to do is to buy ourselves time. The war against the novel coronavirus is taking place on two fronts, and we may have just gained an upper hand on one.
The social front of the fight is being led by politicians, policy makers, and epidemiologists. Physical distancing is implemented as an attempt to slow transmission of the virus. Slower spread offers to lessen the strain on our health systems and give scientists the time they need to develop a vaccine.
While the response of society seems to consume our purview, these restrictions will not completely prevent people from contracting the virus. When they do, a more intimate side of the fight comes into focus â the molecular front. Differing from the societal level, the molecular front sees no politics, emotion or human bias. Instead, everything comes back to the mechanisms our bodies have in place to fight viral infections. The work of scientists studying this front may give us an advantage moving forward.
The immune system specializes in detecting, attacking, and eliminating unwanted pathogens. When a virus enters the body, the immune system sounds an alarm and begins to prepare a response. When the immune system has built up the appropriate army of molecules and antibodies to combat the foreign particle, it generally does a good job at eliminating viruses quickly. Unfortunately, this rarely occurs instantaneously. It can take time for the internal alarm to go off in our bodies and for our immune systems to mount a response. In this time, viruses will hijack and kill more and more cells, increasing the severity of resulting symptoms.
Vaccines work well because they prime the immune system for the virus. In other words, the vaccine tells our immune system what troops of cells to prepare if a certain virus enters. A vaccine is almost like giving our immune systems intel about its opponent before the fight. It allows our bodies to understand what makes the virus unique so it can retaliate effectively. The uniqueness of the novel coronavirus, called SARS-CoV-2, is the glycoproteins on its surface. You can think of these as its weaponry used against the host. If we understand what weapons the virus plans to use before they use them, we can counter the attack by producing cells specifically aimed to disable these weapons and minimize damage. In fact, when primed correctly, the virus can be completely eliminated before we show any symptoms at all. Although many potential vaccines have been pushed into development, this is not a fast process and we are a long way out from anything being widely available.
In the meantime, a significant amount of effort is being put into anti-viral therapies. Instead of priming the immune system pre-infection like vaccines, anti-virals are given to patients shortly after symptoms appear to slow progression of the disease and reduce the chances the virus will be spread to others.
An international collaborative research effort offers a potential breakthrough to gain an upper-hand on the molecular front. Like anti-virals, this proposed treatment works to directly target a virus after it infects a human. What makes it so ground-breaking is that this treatment fights the virus by giving it more of what it wants.
When SARS-CoV-2 enters the body, it binds a protein on the surface of human cells called ACE2. After the virus successfully binds, it gains access into our cells and begins producing more viruses, strengthening its hold on the host and worsening symptoms.
SARS-CoV-2 is best known for its ability to infect cells in the respiratory tract. This is because these cells have ACE2 on their surfaces. When viruses bind ACE2, the receptor cannot perform its normal function. ACE2 functions normally to protect our lungs from damage. Therefore, infection through ACE2 not only gives the virus access to the cells, but it makes our lungs more susceptible to damage. This may explain the high mortality rate of infected individuals.
The recent study proposes to treat infection by giving the virus more ACE2 to bind to, overwhelming it and compromising its ability to attack host cells. The treatment would consist of administering soluble ACE2 to patients. Soluble means the protein is not attached to anything and will float freely throughout the fluids in our body. Therefore, when the virus binds the soluble ACE2, nothing happens, and the virus gets slowed down.
If a vaccine is information the immune system gains before battle, soluble ACE2 anti-viral treatments are like decoys that distract the virus from host cells and slow its attack. While this approach is unlikely to completely eliminate the virus, it gives the immune system the time it needs to build up its defences and mount a strong response.
Early results show tremendous promise for soluble ACE2 as an anti-viral treatment. Researchers found the treatment can reduce viral load by a factor of 1000-5000. Viral load refers to the number of viruses present during infection.
In order to get representative data as fast as possible, the researchers used human stem cells and reprogrammed them to grow into organoids. Organoids are synthetic human organs. These engineered organs are the perfect system for understanding how human tissue might respond to treatment, without testing real patients.
In some ways, this battle is only in its early stages as the number of cases and death tolls will continue to rise. At the social front, continuing physical distancing will buy time for the health system to collect resources and scientists to develop a vaccine. At the molecular front, drugs like soluble ACE2 grant our immune systems time to build up an appropriate response to combat the virus. During situations of this magnitude, we cannot lose sight of the importance of time.
















