Destroy a virus

Full coverage of the coronavirus outbreak. Antibiotics, which are used to fight bacterial infections, attack the bacteria's cell walls, block protein production and stop bacteria from reproducing.

But they aren't effective against viral infections, because viruses don't carry out any of those processes on their own. Rather, viruses need to invade and take over host cells to replicate. But a virus can't break into just any cell in the body. Instead, one of its proteins will bind to another protein — akin to a key fitting into a lock — which then allows the virus to hijack certain cells.

With this outbreak, the coronavirus' so-called spike protein primarily fits "locks" that are present on lung cells, which is why COVID, the disease it causes, is mainly a respiratory illness. Once the invasion takes place, the cell in essence is transformed into a factory that churns out hundreds and hundreds of copies of the virus, based on instructions encoded in its genetic material — RNA, or ribonucleic acid, in the case of the coronavirus.

The human body has evolved defense systems to protect against these kinds of infections. First, cells have a built-in alarm system to detect viral invaders.

The presence of an intruder triggers what's known as an innate immune response, which can involve the host cell releasing a protein that tries to interfere with the virus' replication or can involve the immune system trying to shut down the compromised cells. The work of these reinforcements to try to defeat the virus is typically what causes the symptoms of a viral infection — in other words, it's at this point when a person may come down with a fever and start to feel sick. But viruses are sneaky, Glaunsinger said, and they are often able to fly under the radar and cause a lot of damage before any alarms are triggered and any reinforcements are called in.

By the time an immune response kicks in, it's often too late. When the immune system is finally triggered, it can also kick into overdrive, causing what's called a cytokine storm, which is thought to be the root of some of the most severe coronavirus cases. Adam Lauring, an associate professor of microbiology and immunology at the University of Michigan in Ann Arbor. Of the millions of different viral species identified so far, only about 5, have been characterized in detail.

None of them works in precisely the same way. This should be good news for us when it comes to coronaviruses. However, the bad news is that the coronavirus can be quite stable outside of cells because its spikes, protruding like needles from a pincushion, shield it from direct contact, enabling it to survive on surfaces for relatively long periods. Still, soap or alcohol-based hand sanitizers do a good job of disabling it. But not all coronavirus spikes are alike.

Relatively benign coronavirus variants, which at their worst might cause a scratchy throat and sniffles, attach to cells in the upper respiratory tract — the nasal cavities and throat. Stanford is participating in a clinical trial, sponsored by the National Institutes of Health, to see if antibody-rich plasma the cell-free part of blood from recovered COVID patients who no longer need these antibodies can mitigate symptoms in patients with mild illness and prevent its progression from mild to severe.

Monoclonal antibodies are to the antibodies in convalescent plasma what a laser is to an incandescent light bulb. A worry: Viral mutation rates are much higher than bacterial rates, which dwarf those of our sperm and egg cells. Assistant professor of chemical engineering and subcellular-compartment spelunker Monther Abu-Remaileh , PhD, described two key ways the coronavirus breaks into a cell and seeks comfort there, and how it might be possible to bar one of those entry routes with the right kind of drug.

Grease loves grease. The viral envelope and cell membrane fuse, and the viral contents dump into the cell. The other way is more complicated. To visualize this, imagine yourself with a wad of bubble gum in your mouth, blowing an internal bubble by inhaling, and then swallowing it. Enclosed in this endosome is the viral particle that set the process in motion. Its mission is to become another entity called a lysosome, or to fuse with an existing lysosome.

For this, they need an acidic environment, generated by protein pumps on their surface membranes that force protons into these vesicles. The viral genome gets squirted out into the greater expanse of the cell.

There, the viral genome will find and commandeer the raw materials and molecular machinery required to carry out its genetic instructions. That machinery will furiously crank out viral proteins — including the customized polymerase SARS-CoV-2 needs to replicate its own genome.

A pair of closely related drugs, chloroquine and hydroxychloroquine, have gotten tons of press but, so far, mostly disappointing results in clinical trials for treating COVID Some researchers advocate using hydroxychloroquine, with the caveat that use should be early in the course of the disease. In a lab dish, these drugs diffuse into cells, where they diminish acidity in endosomes and prevent it from building up in lysosomes. The virus remains locked in a prison of its own device.

But only further clinical trials will tell how much that matters. SARS-CoV-2 has entered the cell, either by fusion or by riding in like a Lilliputian aquanaut, stealthily stowed inside an endosome. It must replicate itself in entirety and in bulk, with each copy constituting the potential seed of a new viral particle.

To do both things, the virus needs a special kind of polymerase. Every living cell, including each of ours, uses polymerases to copy its DNA-based genome and to transcribe its contents the genes into RNA-based instructions that ribosomes can read. By changing how that machinery operates, it's possible to stymie the virus's attempts. Drugs that were developed to fight other ailments could have off-label applications for Covid Chloroquine phosphate , used for decades to treat malaria, changes the pH level in human cells, making them less acidic—and less hospitable to certain viruses.

Chloroquine can also reduce the lung inflammation that kills some patients with severe Covid infection. One problem: An overdose can be fatal. A class of drugs called protease inhibitors, long used to treat HIV and hepatitis C, disrupt the viral replication process.

Proteases are like molecular scissors; once inside the host cell, SARS-CoV-2 uses them to slice long strands of protein into usable chunks. Without these scissors, the virus's life cycle can't continue. Another class of medications targets an enzyme called polymerase, which strings together copies of the virus's genetic material, RNA, inside the host cell.

Two promising candidates in this category—remdesivir, originally developed to treat Ebola, and favipiravir , first deployed against the flu—impersonate the building blocks of RNA and get incorporated into the chain.

Once they're there, the polymerase can't add new pieces, and replication halts. This article appears in the May issue. Subscribe now. Sara Harrison is a freelancer who covers science and business. Contributor Twitter.