The Physics of Viruses

Russ Hobbie and I don’t talk much about viruses in Intermediate Physics for Medicine and Biology. The closest we come is in Chapter 1, when discussing Distances and Sizes.

Viruses are tiny packets of genetic material encased in protein. On their own they are incapable of metabolism or reproduction, so some scientists do not even consider them as living organisms. Yet, they can infect a cell and take control of its metabolic and reproductive functions. The length scale of viruses is one-tenth of a micron, or 100 nm.

In response to the current Covid-19 pandemic, today I’ll present a micro-course about virology and suggest ways physics contributes to fighting viral diseases.

I’m sometimes careless about distinguishing between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the Covid-19 disease it produces. I’ll try to be more careful today. In this post, I’ll refer to SARS-CoV-2 as “the coronavirus” and let virologists worry about the distinctions between different types of coronaviruses. The “2” at the end of SARS-CoV-2 differentiates it from the similar virus responsible for the 2002 SARS epidemic.

The coronavirus is an average sized virus: about 100 nm in diameter. It is enclosed in a lipid bilayer that contains three transmembrane proteins: membrane, envelope, and spike. The spike proteins are the ones that stick out of the coronavirus and give it a crown-like appearance. They’re also the proteins that are recognized by receptors on the host cell and initiate infection. A drug that would interfere with the binding of the spike protein to a receptor would be a potential Covid-19 therapy. A fourth protein, nucleocapsid, is enclosed inside the lipid bilayer and surrounds the genetic material.

Viruses can encode genetic information using DNA or RNA. The coronavirus uses a single strand of messenger RNA, containing about 30,000 bases. For those who remember the central dogma of molecular biology— DNA is transcribed to messenger RNA, which is translated into protein — will know that the RNA of the coronavirus can be translated using the cell’s protein synsthesis machinery, located mainly in the ribosomes. However, only one protein is translated directly: the RNA-dependent RNA polymerase. This enzyme catalyzes the production of more messenger RNA using the virus’s RNA as a template. It is the primary target for the antiviral drug remdesivir. RNA replication lacks the mechanisms to correct errors that cells use when copying DNA, so it is prone to mutations. Fortunately, the coronavirus doesn’t seem to be mutating too rapidly, which makes the development of a vaccine feasible.

The life cycle of the coronavirus consists of 1) binding of the spike protein to an angiotensin-converting enzyme 2 (ACE2) receptor on the extracellular surface of a target cell, 2) injection of the virus RNA, along with the nucleocapsid protein, into the cell, 3) translation of the RNA-dependent RNA polymerase by the cell’s ribosomes and protein synthesis machinery, 4) production of multiple copies of messenger RNA using the RNA-dependent RNA polymerase, 5) translation of this newly-formed messenger RNA to make all the proteins needed for virus production, 6) assembly of virus particles inside the cell, and 7) release of the virus from an infected cell by a process called exocytosis.

Our body responds to the coronavirus by producing antibodies, Y-shaped proteins about 10 nm in size that can bind specifically to an antigen. Antibodies formed in response to Covid-19 bind with the spike protein on the coronavirus’s surface. The details about how this antibody blocks the binding of the spike protein to the ACE2 receptor in our bodies is not entirely clear yet. Such knowledge could be helpful in designing a Covid-19 vaccine.

How can physics contribute to defeating Covid-19? I see several ways. 1) X-ray diffraction is one method to determine the structure of macromolecules, such as the coronavirus’s spike protein and the RNA-dependent RNA polymerase. 2) An Electron microscope can image the coronavirus and its macromolecules. Viruses are too small to resolve using an optical microscope, but (as discussed in Chapter 14 of IPMB) using the wave properties of electrons we can obtain high-resolution images. 3) Computer simulation could be important for predicting how different molecules making up the coronavirus interact with potential drugs. Such calculations might need to include not only the molecular structure but also the mechanism for how charged molecules interact in body fluids, often represented using the Poisson-Boltzmann equation (see Chapter 9 of IPMB). 4) Mathematical modeling is needed to describe how the coronavirus spreads through the population, and how our immune system responds to viral infection. These models are complex, and require the tools of nonlinear dynamics (learn more in Chapter 10 of IPMB).

Ultimately biologists will defeat Covid-19, but physicists have much to contribute to this battle. Together we will overcome this scourge.

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