Paxlovid Virtual Reality demo

Tom Goddard
March 24, 2023
for UCSF Biophysics student applicants 11:15 - noon.

Setup

• Setup Quest Pro standalone VR
  • Copy mpro_peptide.glb, nirmatrelvir.glb and ritonavir.glb to Quest Pro using USB cable and Windows file browser.
  • Start the LookieAR app.
  • Show Send to Quest tool in ChimeraX and set adb path to "C:/Program Files/Unity/Hub/Editor/2022.2.5f1/Editor/Data/PlaybackEngines/AndroidPlayer/SDK/platform-tools/adb.exe".
• Setup screencast using from QuestPro to PC using Camera icon in headset and pressing Cast.
  • Join RBVIVR wifi network with PC. Need to be on same network as Quest Pro to screencast.
  • Go to oculus.com/cast in Chrome (does not work in Firefox).
  • Sometimes takes up to a minute or two to connect and start screen casting.
  • Use VizVault projector and put screencast in "wide-screen" mode in browser.
• Setup ChimeraX PC VR.
  • The Quest Pro is somewhat glitchy over QuestLink so instead use Vive Pro.
  • Turn on vive pro link box.
  • Start ChimeraX and open pax.cxs session.
  • Test with "vr on" command.

Intro

Look at how paxlovid disables sars-cov-2 and at how the virus may mutate to disable the drug. Expect to have 7 students to try VR.

• Give each visitor a hand controller to try the buttons. Have 6 controllers for two Quest 2 and one Quest Pro headset. Grip button to move, thumbstick to zoom, A/X for user interface, trigger button to click buttons.
• Mention if you feel uncomfortable, take headset off.

Steps

1. sars-cov-2 main protease. Open sars-cov-2 main protease with natural ligand (PDB 7dvw), dimer colored and showing atomic interactions in binding site. Show how to walk around, wall boundary, how to translate and rotate and zoom. Look at where peptide ligand is cut.
2. nirmatrelvir and ritonavir. Open nirmatrelvir and ritonavir. Show how to move each individually by pointing + grip button. Explain ritonavir interacts with cytochrome P450 which slow nirmatrelvir degradation / metabolism. Note peptide-like backbone of nirmatrelvir, a peptido-mimetic drug. Try placing nirmatrelvir in binding side overlapping natural peptide.
3. nirmatrelvir bound to protease. Send nirmatrelvir bound protease from ChimeraX to headset using "Send to Quest" tool. Explain how models created in ChimeraX are sent to headset as GLTF scene files. Look at covalent binding of drug to protease. Can try to align drug to bound form -- nearly matches, lone drug is near low energy state. Look at E166V resistance mutation site and T21I and L50F compensatory mutations.
4. hydrogen bonds and drug resistance mutations. Switch to ChimeraX VR by AirLink. Show how to move and zoom and show user interface. Use select mode to select nirmatrelvir then show hbonds with toolbar button. Note E166 makes hydrogen bond.
5. xray density. Use contour mode to adjust x-ray density contour level. Note E166 density is weak.
6. E166V mutation. Use swapaa mode mutate E166 to valine in VR. Do the same mutation with the peptide bound structure to see if it will interfere with viral replication.
7. Energy minimization. Use energy minimize on V166 in peptide bound conformation to see if much moves. Not much moves. Can also try tug mouse mode to tug V166 and see how it settles back when minimized. VR will flicker so useful to use a fixed headset view while doing these steps.