AlphaFold Database adds viral protein pairs from 2,800 human-infecting viruses

Viruses were the blind spot in a database that already holds most known proteins, Grove said ^[6]. Their genomes often encode one long polyprotein that the cell then cuts into working pieces, so the edges of any single protein are hard to read from sequence alone and the resulting structure predictions come out incomplete ^[7]. Researchers at the Swiss Institute of Bioinformatics in Geneva worked through thousands of these cut proteins to fix accurate sequences first ^[8]. "Many viral proteins do not act individually, they act in concert with partners," said Joe Grove, a molecular virologist at the University of Glasgow who worked on the release ^[5].

The run was large and the filter was strict. The team took 41,774 proteins from about 2,800 viruses, among them the causes of mpox, measles and hepatitis B, and used AlphaFold2 to model 40,746 pairs of identical proteins and nearly 1.7 million pairs of different ones ^[9][10]. Only 2,749 of the identical pairs cleared the accuracy bar for the curated set, about one in fifteen, along with 5,279 of the mixed pairs ^[11][13]. That leaves 8,028 vetted pairs in the new portal, though every prediction was posted publicly ^[12][4].

Two limits matter for the pandemic use in view. The models stop at pairs, and they do not include the sugar molecules that coat many viral proteins and help them evade the immune system ^[14]. Many of the proteins a vaccine team would aim at sit in larger assemblies. The SARS-CoV-2 spike is three identical proteins, and so is HIV's entry protein; in many cases the two-protein predictions for these were not accurate enough to include, Grove said ^[15]. Trimer predictions are the obvious next step, according to EMBL-EBI's Sameer Velankar, though for bigger complexes it is not always clear how many copies of each part they contain ^[16].

"Making these data open is critical for understanding viral diagnostics and developing treatments and vaccines," said Jo McEntyre, interim director of EMBL-EBI. "They can support faster and more effective responses to future pandemics. They also cover lesser-studied viruses and lower the barriers for scientists in low-resource settings, who are confronting outbreaks firsthand." ^[17]

The push to have such structures early comes from pandemic-planning numbers. The Center for Global Development puts the chance of a COVID-scale pandemic by 2050 at nearly 50 percent ^[18]. The 100 Days Mission wants safe treatments and vaccines ready within 100 days of a new threat being identified, and the collaborators note that hitting that needs structural information in hand well before a virus turns global ^[19]. They planned to announce the release on Sept. 24 at a CEPI and World Economic Forum roundtable, a day ahead of the UN's high-level meeting on pandemic prevention in New York ^[20].

Grove wants to test it against his own work on viral entry proteins. "The proof of the pudding is going to be in putting that data out there and having teams such as my own start to drill down," he said ^[24].