Description

COVID-19: Molecular Basis of Infection

Overview: This case is an adaptation of the original COVID-19: Molecular Basis of Infection case which discusses how the SARS-Cov-2 Spike protein binds to Angiotensin-converting enzyme 2 (ACE2), a protein found on the surface of many human cells initiating infections. After reviewing some introductory materials about coronavirus life cycle, the case begins with watching a video that introduces the structures of the SARS-Cov-2 spike protein, human ACE2 protein, and their complex. By comparing sequences and structures of the spike protein from SARS-Cov2 and SARS-Cov, the virus that caused the epidemic in 2002-2003 some insights are available for why the new virus has caused a pandemic and what alternatives to social distances can be considered to prevent the spread of infection.

Learning Objectives: The case was developed at the interface of biology and chemistry to explore SARS-Cov-2 attachment on human cells and infection. It introduces students to various bioinformatics and molecular visualization tools and approaches used for comparing protein structures and vaccine development. By the end of the case, students should develop some basic understanding of biomolecular structure-function relationships and how that can impact infection and disease. Following the completion of the module, the students should be able to:

• retrieve protein sequences from public repositories
• search for similar protein sequences to a query sequence using open license software
• align and compare protein sequences using open license software
• use RCSB Protein Data Bank to retrieve structural information about proteins whose 3D structure is deposited in the databank
• explore molecular interactions by visualizing available 3D protein structures with freely available online tools
• explain the molecular basis of SARS CoV-2 infection through viral entry to the cell.
• explain the differences between SARS CoV-2 and SARS CoV interaction with the host cell at the molecular level and discuss their impact on infection
• propose alternative ways to social distancing to prevent infection based on a molecular understanding of virus entry to the cell

Molecules explored: The key molecules explored here include the SARS-Cov-2 spike protein, human ACE2 protein, and the structure of their complex. Structures of SARS-Cov-2 spike protein with antibodies are also explored.

Implementation: The adaptation is specifically designed to enhance the modular structure of the case so that it can be used entirely in a flipped format (if desired) in its entirety or in parts based on students’ prior preparation.  The major difference between this adaptation and the original case is in Part 3 where the students are asked to draw conclusions based on provided structural figures rather than required to create their own figures.  In this adaptation the skills needed to navigate RCSB PDB site and use deposited structures to create visual stories are developed and used only in Part 2, allowing Part 3 to be also usable as an independent module for instructors who have introduced molecular visualization and literacy to their students through the study of structural papers. Similarly, it allows Part 3 of this adaptation to be used as an assessment tool rather than a part of the skill developing activity.

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