Let’s talk about how we developed a new mechanism of action, taking the example of a SARS-CoV-2 project.
SARS-CoV-2, the cause of the COVID-19 pandemic, is a coronavirus from the Coronaviridae family. Coronavirus disease 2019 has had a catastrophic effect on the world’s demographics resulting in more than 6 million deaths worldwide, emerging as the most consequential global health crisis since the era of the influenza pandemic of 1918.
Since the beginning of the coronavirus pandemic, the whole world has become concerned about finding an effective treatment for the disease. Clinical guidelines have changed a lot of times, new drugs have come onto the market, and old and well-known drugs have been found to have an effect against coronavirus disease.
Our medical animation studio worked on several COVID-19 projects, especially in two main directions. Firstly, the structure, life cycle of coronavirus, and the pathogenesis of coronavirus disease. These are the main targets of drug therapy. And secondly, it was a presentation of the mechanism of action of anti-COVID-19 drugs at a molecular level. Often we showed processes that were new to viewers. And we think that scientifically accurate medical animation is the best way to present such in-depth biological processes.
So SARS-CoV-19 has become one of the most popular topics for scientific 3D animation worldwide. Our studio also has made several detailed 3D models of the coronavirus with all its main proteins, including the membrane, envelope, and spike proteins. The exact 3D model also allows us to look inside the virus and see the genetic information. Did you know that coronaviruses’ RNA genome is the longest among all RNA viruses? The genome encodes about 29 proteins, including the spike protein, a key factor in the infection cycle.
Spike proteins allow coronaviruses to penetrate host cells which is the first step of viral infection. A spike glycoprotein on the viral envelope of the coronavirus can bind to specific receptors on the membrane of host cells called ACE2, a specific functional receptor for SARS-CoV-2. SARS-CoV-2 can enter only ACE2-expressing cells. The receptor-binding domain of the spike glycoprotein binds to the subdomain I of ACE2, which causes membrane fusion of the virus and the host cell, and viral RNA is subsequently released into the cytoplasm, establishing infection.
ACE2 has two conformational states, i.e., open and closed, for its native and ligand-binding states through a significant hinge-bending motion. In the opened state, ACE2 opens wide from its active site to wait for a ligand to enter. Since the SARS-CoV-2 spike protein was shown to bind the open form of ACE2, small molecule drugs that modify the ACE2 conformation to a closed-form could inhibit RBD interactions.
One project of our animation studio was about a drug of H1-receptor antagonists. This drug went through several studies, and the results reported that this H1 antagonist might be efficient in reducing the nasal viral load of patients tested positively for SARS-CoV-2. The outcomes were very promising, and our task was to show the drug’s mechanism of action.
We analyzed several scientific articles and found that the drug inhibits ACE2 very interestingly. To show this process, we created a 3D model of a cell membrane consisting of a double layer of phospholipids. We placed a scientifically accurate model of the receptor, which we downloaded from the pdb protein data bank. According to the scenario, the coronavirus appeared in the frame, approached the cell membrane, and right before the interaction, an H1 antagonist molecule appeared in the frame and binding with the active site of ACE2, which caused the morphing of the receptor model. Its conformation changed from open to closed, and because of that, the virion couldn’t interact with ACE2 anymore. This scene took only about 20 seconds, but this is more than enough in scientific animation to portray the key message.
Thus, we present the new mechanisms of action to viewers in a prominent, understandable, and scientific manner. Detection of new mechanisms of action is an essential strategy for responding to the COVID-19 pandemic, and our medical animation studio is ready to bring these crucial points to people.
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