Gates Package — page 1002

drug have gotten much better in the past thirty years, with the advent of a field called structureguided discovery. In structure-guided discovery, instead of testing each possible compound in a lab, scientists can program computers to create 3D models of vulnerable parts of the virus and then design molecules that attack those targets. Moving the search for compounds from laboratory experiments to structure-guided discovery is like playing chess on a computer instead of a board--the game still happens, but not in a physical space. And just as with chess, structureguided discovery has become more sophisticated with the growing processing power of computers and advances in artificial intelligence. Here's how it worked for Paxlovid, the antiviral announced by Pfizer in late 2021. Scientists had identified how COVID hijacks parts of your cells to make more copies of itself (these parts are sequences of amino acids, the building blocks of proteins). Using this knowledge, they designed a molecule that operates like an undercover cop conducting a sting operation. It mimics most of the sequence of amino acids that COVID will seek out, but it's missing key pieces of the sequence, so it disrupts the life cycle of the virus. There are several stages of the life cycle that can be disrupted. In the case of HIV antivirals, by far biggest category of antivirals, we have ones that attack each stage, and we combine three of them so that the virus is very unlikely to mutate to stop them from working all at once.. Even though we can now run virtual experiments very quickly on a computer, sometimes researchers still need to do the real thing--to match a compound with the protein from a virus in a lab and see what happens. But technology is changing this approach too. In a process known as high-throughput screening, robotic machines can run hundreds of experiments at a time, mixing compounds and proteins and then using various methods to