{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T05:04:25Z","timestamp":1783919065967,"version":"3.55.0"},"reference-count":116,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as one of the most significant global health crises in recent history. Coronaviruses are a diverse group of RNA viruses classified into alpha, beta, gamma, and delta genera, with SARS-CoV-2 belonging to the beta-coronavirus family. The virus exhibits high transmissibility and causes a wide spectrum of clinical manifestations ranging from mild respiratory symptoms to severe complications such as acute respiratory distress syndrome, multi-organ failure, and death, particularly among elderly and immunocompromised individuals. Structurally, SARS-CoV-2 possesses a large single-stranded RNA genome encoding major structural proteins, including spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins, which play critical roles in host-cell recognition and viral infection. Understanding the molecular mechanisms of virus\u2013host interactions, especially protein\u2013protein interactions (PPIs), is essential for uncovering viral pathogenesis and identifying potential therapeutic targets. Traditional experimental techniques for PPI detection, such as yeast two-hybrid and affinity purification methods, are often expensive, labor-intensive, and prone to inaccuracies. Consequently, computational approaches based on machine learning (ML) and deep learning (DL) have gained significant attention for efficient and scalable PPI prediction. These methods use diverse biological information, including protein sequences, structural features, genomic data, Gene Ontology annotations, and interaction networks, to model complex biological relationships. This survey reviews computational approaches to PPI prediction, highlighting ML- and DL-based techniques, methodological advances, performance evaluation practices, and limitations that affect benchmark comparability. It also discusses biological databases and data sources commonly used in PPI studies and explicitly considers how models trained in coronavirus-centered settings may generalize to other viral families with different mechanisms of host interaction.<\/jats:p>","DOI":"10.3390\/ijms27136034","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:43:14Z","timestamp":1783345394000},"page":"6034","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Machine Learning and Deep Learning Frameworks for Human\u2013Virus Protein\u2013Protein Interaction Prediction: Emerging Architectures, Methods, Benchmarks, and Challenges"],"prefix":"10.3390","volume":"27","author":[{"given":"Subhadeep","family":"Basu","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Amity University, Noida 201313, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dipanwita","family":"Adhikary","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biochemical Engineering, Indian Institute of Technology, Kharagpur 721302, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4431-1404","authenticated-orcid":false,"given":"Kuntal","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Machine Intelligence Unit, Indian Statistical Institute, Kolkata 700108, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swarup","family":"Chattopadhyay","sequence":"additional","affiliation":[{"name":"School of Computer Science and Engineering, XIM University, Bhubaneswar 751013, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shramana","family":"Deb","sequence":"additional","affiliation":[{"name":"Centre for Neurovascular Research, Manipal Group of Hospitals, Kolkata 700099, India"},{"name":"Department of Neurology, Manipal Group of Hospitals, Kolkata 700099, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4288-7661","authenticated-orcid":false,"given":"Ritwick","family":"Mondal","sequence":"additional","affiliation":[{"name":"Centre for Neurovascular Research, Manipal Group of Hospitals, Kolkata 700099, India"},{"name":"Department of Neurology, Manipal Group of Hospitals, Kolkata 700099, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4906-2619","authenticated-orcid":false,"given":"Jayanta","family":"Roy","sequence":"additional","affiliation":[{"name":"Centre for Neurovascular Research, Manipal Group of Hospitals, Kolkata 700099, India"},{"name":"Department of Neurology, Manipal Group of Hospitals, Kolkata 700099, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1056-1568","authenticated-orcid":false,"given":"Anjan","family":"Chowdhury","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Engineering, Indian Institute of Technology, Dhanbad 826004, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1769-4809","authenticated-orcid":false,"given":"Juli\u00e1n","family":"Benito-Le\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Neurology, 12 de Octubre University Hospital, 28041 Madrid, Spain"},{"name":"Group of Neurodegenerative Diseases, Hospital Universitario 12 de Octubre Research Institute (Imas12), 28041 Madrid, Spain"},{"name":"Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), 28031 Madrid, Spain"},{"name":"Department of Medicine, Faculty of Medicine, Complutense University of Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.ijid.2020.01.009","article-title":"The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health\u2014The latest 2019 novel coronavirus outbreak in Wuhan, China","volume":"91","author":"Hui","year":"2020","journal-title":"Int. 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