We need more investment in broad-spectrum antivirals, or medicines that defend people against many viruses simultaneously. Unfortunately, it’s hard to do this! There are more than 60 types of adenovirus alone, for example, each carrying unique proteins. Designing an antiviral that blocks all of these is very difficult. Instead of designing drugs, then, what if we harnessed physics? After all, every virus enters a human cell by “pressing” or “pushing” on it. If the cell can sense these physical forces, and somehow use them to trigger resistance, then perhaps we could develop more universal antivirals. A new paper hints at this possibility, and it stems from a weird discovery that came before. A few years ago, scientists grew human cells at low densities and infected them with viruses. When they did this, each cell produced large amounts of the virus; they were easily infected. When this experiment was repeated with cells grown at a high density, though, each cell (on average) produced much less virus. Something with this “crowding” was blocking viral replication. These scientists speculated that a protein, called Piezo1, might be involved. Piezo1 is a mechanically-sensitive calcium channel. Upon activation (with vibrations, touch, or small molecules) it opens, allowing calcium to pour into the cell. This calcium influx then causes the cell membrane to stiffen, though the mechanism for this is not clear. For this new paper, then, Chinese scientists grew human cells at low or high densities, infected them with many different viruses, and studied Piezo1’s involvement. When they grew cells at high density, but knocked out Piezo1, each cell produced more viruses. Similarly, when cells were grown at a low density and infected with viruses, while being shaken on a plate, they became more resistant to infection. This effect disappeared when Piezo1 was deleted. Similarly, when the authors overexpressed Piezo1 in HEK293T cells, it suppressed viral replication (by about 10-fold). This effect was not observed with Piezo2, another mechanosensitive ion channel. The researchers next used Piezo1 agonists to simulate this effect. A small molecule, called Yoda1, binds and activates Piezo1. Treating cells with Yoda1 reduced viral titers in human cells by 10-100 fold. The researchers also infected mice with lethal doses of various viruses (enteroviruses, coxsackievirus, influenza A), treated the animals with Yoda1 (or controls), and found that treated mice were more likely to survive. This work is interesting, but also flawed. For one, the molecular mechanism linking Piezo1 —> viral resistance is not described. They think it has something to do with membrane stiffening, but nobody actually knows *how* Piezo1 activation causes this. Another issue is the methods. For one experiment, the researchers infected mice with viruses and then shook them on little platforms. This, apparently, increased their resistance. But the scientists never actually explain the method, or what the platforms look like, or what the device settings were. It’s all a bit vague and difficult to believe. Still, searching for “universal” or physical mechanisms to build broad-spectrum therapies is exciting. Rather than make small molecules that target one pathogen, we ought to think about unifying, biophysical principles that can be used to exert control more widely.