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SARS-CoV-2 Main Protease & Potential Inhibitors: An exploration of Nanome and SARS-COVID-19

CSCI 1951T (Spring 2023) | Project 01

Mohammed Akel

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Motivation

  • Once a cell is infected by COVID-19, a number of molecules is produced that the virus needs to replicate new viruses. Most notably, is the proteases that play an essential role in cutting the protein into functional pieces. The main protease of coronavirus makes most of these cuts
  • The protease has an active site that potential inhibitors can bound to

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SARS main protease (top) and papain-like protease (bottom), with inhibitor in turquoise.

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How did it change?

  • A brief description of nanom and its most important features
  • Visualizing the COVID-19 main protease structure with an emphasis on the active site
    • Could have provided more context and information
    • Individualized culture
  • Explore fragment-based lead drug discovery
    • Instead, we explored an additional visualization: COVID-19 Spike Protein
  • Grow/combine/create fragments to produce a lead for a small molecule inhibitor that binds to the active site with a higher affinity
    • Focused on building molecules in general
  • Compare our molecules and analyze their real life applicability

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Evaluation

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Evaluation - Literature Review

  • A brief literature review shows that there is significant hype about platforms like Nanome
  • saving organizations tens of thousands of dollars every year
  • shorten the average 12–18 month lead optimization timeline for new drugs
  • enhance communication between scientists from different disciplines
  • Nanome’s clients
    • Roivant
    • LifeArc

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Evaluation - In Class Activity

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Evaluation - In Class Activity

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Evaluation - In Class Activity

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Evaluation - In Class Activity

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Evaluation - In Class Activity

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Evaluation - 2D vs 3D & immersive vs web-based (or Desktop based)

  • Part 03 under the Nanome Evaluation Page
  • Some typical problems associated with classic 2D interfaces:
    • lack of natural spatial understanding and interaction
    • a limited field of view.
  • Oculus Quest headsets
    • Not physically attached to a computer
    • everyone can view structures together and collaborate on them in real-time

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Evaluation Comparable (Open Source) Models:

  • Protein VR
  • Narupa
  • PyMOL, ChimeraX, VMD, Maestro & Discovery Studio

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Wiki Contributions

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Wiki Contribution #1 | Updating Nanome’s landing, set up and features pages

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Wiki Contribution #2 | Nanome’s Evaluation Page

https://sites.google.com/view/brown-vr-sw-review-2018/vr-visualization-software/nanome/nanome-evaluation

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Wiki Contribution #3 | VR in Pandemic Prevention and Preparedness

https://sites.google.com/view/brown-vr-sw-review-2018/applications-of-vr/vr-in-pandemic-prevention-and-preparation?authuser=0

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Wiki Contribution #4 | VR during the SARS-COVID-19 Pandemic

https://sites.google.com/view/brown-vr-sw-review-2018/applications-of-vr/vr-in-pandemic-prevention-and-preparation/vr-covid-19?authuser=0

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Wiki Contributions (from the original plan)

  • Improve the existing nanome tutorials
    • Added a full page on evaluating Nanome using multiple methods
  • A page on visualizing molecular structures (including, web, desktop applications, mobile apps)
    • Redundant but the materials exist
  • A page on evaluating VR softwares related to molecular visualization (including a comparison of different softwares as well as 2D vs desktop features vs immersive features)
  • A series of articles on how VR contributed/could contribute to our understanding of the SARS-COVID-19 virus and outbreak
    • Added a literature review of most update applications of VR in Pandemics
  • A page with screenshots from in class activity

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Project 02 - Augmentative and Alternative Communication in Immersive Environments

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References