Researchers Have Come Up With an Idea to Deceive Coronavirus
Scientists are attempting to trick the coronavirus in such a way that it will not enter our cell.
SARS-CoV-2 enters our cells via ACE2 receptor protein found on the cell surface. This entry is initiated by the binding of ACE2 with the spike (S) protein of this virus. Scientists have introduced an idea to deceive coronavirus by using this binding affinity.
Since the beginning of the COVID-19 vaccine production effort, researchers are adopting various approaches to prevent this binding. Some researchers are producing monoclonal antibodies to occupy the binding site of ACE2. On the other hand, other groups of scientists are trying to find a vaccine that will trigger our body to produce antibodies on its own.
But Chan and his team have followed a very different approach. They produced an engineered ACE2 receptor that will deceive coronavirus. In scientific language, this type of receptor is called the decoy receptor.
ACE2 means angiotensin-converting enzyme. This dimeric enzyme can be found on the surface of epithelial cells of different types of tissue (e.g.; lung, heart, blood vessels, kidneys, and gastrointestinal tract). It mainly helps to reduce blood pressure and inflammation.
On the other hand, the S protein of SARS-CoV-2 is a trimeric protein that has two parts (S1 and S2). The S1 part contains a special region called the receptor-binding domain (RBD). Due to this RBD, the S protein of coronavirus can bind firmly with ACE2 and then enters our cell.
Chan et al. showed that how the entry of coronavirus in our cell can be prevented by engineered ACE2 with higher binding affinity. The idea is that when the S protein of coronavirus will find an ACE2 receptor with higher binding affinity instead of binding to our cell it will bind to that engineered ACE2 receptor. Such a modified ACE2 variant is sACE2_2.v2.4, which has a 10 fold higher affinity for S protein than normal ACE2.
Mutation means changes in the sequence of DNA, RNA, or Protein. Scientists have noticed that mutations in the ACE2 protein also result in changes in its affinity for the S protein. By utilizing this idea, Chan et al. have found out a mutational variant of ACE2 that bind with S protein more firmly than a normal one (e.g; sACE2_2.v2.4).
Since this sACE2_2.v2.4 has a 10 fold higher affinity for S protein of coronavirus when it will be used as a therapeutic agent, all viruses will bind with it. As a result, the virus will not enter our cells. Additionally, this sACE2_2.v2.4 can have catalytic activity to kill the virus.
Moreover, this engineered sACE2_2.v2.4 also works against SARS-CoV-1 ( which causes SARS). So scientists are hopeful that this decoy receptor will be effective against a diverse type of coronavirus.
The concept of the decoy receptor is not absolutely new. Earlier, the decoy receptor was created as an antiviral agent against several viruses like HIV, rhinovirus, etc. Though this type of therapeutic option is not yet clinically approved as antiviral medication, but a decoy receptor designed for common cold showed promising efficacy in human trial.
A typical risk in the usual antibody-dependent vaccine strategy is that it may sometimes accelerate the infection of the virus against which it has been developed. Engineered ACE2 as a decoy receptor does not have such risk. Moreover, recombinant ACE2 has clinical safety records as treatment for pulmonary arterial hypertension and acute respiratory distress.
But, such engineered ACE2 has a major disadvantage, which is short half-life. For that reason it yet this can not be used as a preventive vaccine against COVID-19. However, experts believe that it can be used as a curative treatment for COVID-19 disease, which not only inhibits the virus from invading our cell, it also helps to reduce the symptoms of the disease.
Scientists from every part of the world are working tirelessly to find an appropriate protective SARS-CoV-2 vaccine. By the end of this year, we will get the clinical result of many first generation vaccines. Additionally, more specific information about the structure of ACE2 and S protein will broaden the opportunity for many new therapeutic options.
