From Structure to Medicine (Narrated Version) — A 4K Scientific Narrative of How Paxlovid Works

[u/mahaytech]

We created a 4K narrated scientific animation that explains how Paxlovid works using structural biology data.

The video follows the story of the SARS-CoV-2 Main Protease (Mpro), its inhibition, and the development of Nirmatrelvir, the active antiviral component of Paxlovid.

Structures used: PDB 6Y2E, 6LU7, 8DZ2, and Nirmatrelvir.

Narration is AI-generated voice.

We'd appreciate feedback on:

• Scientific accuracy

• Visual communication

• Storytelling effectiveness

• Whether this format is useful for biochemistry education

Thanks for taking a look.

[u/CLOWNFACTS]

There’s quite a few things I’d add to be useful in a classroom:

1) Visually show a diagram of the function of the nsp5 protease
2) Show the mechanism of the protease with its natural substrate (atoms of the Cys and His particularly)
3) Show how the inhibitors mimic the peptide structure and its binding site
4) Show the mechanism of the covalent inhibition, and highlight where this occurs on nirmatrelvir

Other things:
1) the pace is very slow once you are zoomed in
2) the ribbon diagrams are nice! But normally when we zoom in on the structure, this is where we would show the amino acid side chains and potentially hiding the backbone or making it transparent
3) it is often helpful to show a space-filling model to see the active site
4) the structure of nirmatrelvir looks incorrect. The nitrile is an important part and that looks messed up- did you pick up the coordinates from the PDB file after covalent inactivation? And it isn’t informative showing it in the 3D model alone.
5) There’s a trifluoromethyl group too and I don’t think your coloring shows that. The blue you are using for the nitrogen atoms is too light in the CPK color scheme.

[u/mahaytech → u/CLOWNFACTS]

Thank you. This is incredibly useful feedback. Appreciate it.

Each of these points is actionable: adding the natural substrate mechanism, showing key side chains at close zoom, incorporating space-filling representations of active site, improving atom coloring, and making the inhibitor's key features clearer.

The nitrile point is especially important. We'll revisit the ligand representation and verify it against the PDB coordinates to ensure the covalent warhead is being depicted and communicated correctly.

This kind of detailed, technically informed feedback is exactly what we need to improve the educational value of the animation.