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Recent models, including ESM2, ESM3, AlphaGenome, Evo-1, and Evo-2, adapt natural language processing principles to the biological domain by learning high-dimensional hidden representations that capture evolutionary constraints, structural patterns, and functional motifs. This mini-review summarizes recent developments in devising and applying such models, emphasizing viral protein analysis. We highlight studies that have leveraged sequence-based LLMs in the protein domain (i.e. protein language models, or PLMs) for important application tasks such as viral protein annotation, variant effect prediction, and immune escape characterization. Additionally, we present a benchmark evaluation of these state-of-the-art protein language models to evaluate their core ability to capture evolutionary relationships between viral protein sequences. By discussing the opportunities and challenges of PLMs, the review outlines a road map for the potential application of LLMs in empowering virology research and pathogen surveillance.<\/jats:p>","DOI":"10.1093\/bib\/bbag377","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T19:54:08Z","timestamp":1784318048000},"source":"Crossref","is-referenced-by-count":0,"title":["Decoding viral protein sequences by large language models"],"prefix":"10.1093","volume":"27","author":[{"given":"Tianyi","family":"Fei","sequence":"first","affiliation":[{"name":"GMU-GIBH Joint School of Life Sciences, Guangdong Provincial Key Laboratory of Protein Modification and Disease, The Guangdong-Hong Kong-Macao Joint Laboratory for Cell Fate Regulation and Diseases , Guangzhou Medical University, Guangzhou 511436, Guangdong Province,","place":["China"]},{"name":"Guangzhou National Laboratory, No. 9 XingDaoHuanBei Road, Guangzhou International Bio Island , Guangzhou 510005, Guangdong Province,","place":["China"]},{"name":"School of Life Sciences and Technology, ShanghaiTech University , No. 393 Middle Huaxia Road, Shanghai 201210,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqi","family":"Li","sequence":"additional","affiliation":[{"name":"GMU-GIBH Joint School of Life Sciences, Guangdong Provincial Key Laboratory of Protein Modification and Disease, The Guangdong-Hong Kong-Macao Joint Laboratory for Cell Fate Regulation and Diseases, Guangzhou Medical University , Guangzhou 511436, Guangdong Province,","place":["China"]},{"name":"Guangzhou National Laboratory , No. 9 XingDaoHuanBei Road, Guangzhou International Bio Island, Guangzhou 510005, Guangdong Province,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyue","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangzhou National Laboratory , No. 9 XingDaoHuanBei Road, Guangzhou International Bio Island, Guangzhou 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Guangdong-Hong Kong-Macao Joint Laboratory for Cell Fate Regulation and Diseases, Guangzhou Medical University , Guangzhou 511436, Guangdong Province,","place":["China"]},{"name":"Guangzhou National Laboratory , No. 9 XingDaoHuanBei Road, Guangzhou International Bio Island, Guangzhou 510005, Guangdong Province,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0295-3994","authenticated-orcid":false,"given":"Tao","family":"Zeng","sequence":"additional","affiliation":[{"name":"GMU-GIBH Joint School of Life Sciences, Guangdong Provincial Key Laboratory of Protein Modification and Disease, The Guangdong-Hong Kong-Macao Joint Laboratory for Cell Fate Regulation and Diseases , Guangzhou Medical University, Guangzhou 511436, Guangdong Province,","place":["China"]},{"name":"Guangzhou National Laboratory , No. 9 XingDaoHuanBei Road, Guangzhou International Bio Island, Guangzhou 510005, Guangdong 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