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In this study, we screened 41 anhydride\u2010modified proteins and found that 3\u2010hydroxyphthalic anhydride\u2010modified \u03b2\u2010lactoglobulin (3HP\u2010\u03b2\u2010LG), a clinically used anti\u2010HPV agent, was highly effective in inhibiting infection of vaccinia virus Tiantan strain (VACV\u2010VTT) and MPXV. Mechanistic studies demonstrated that 3HP\u2010\u03b2\u2010LG bound to the virus, not the host cell, by targeting the early stage of virus entry, possibly through the interaction between the amino acids with negatively charges in 3HP\u2010\u03b2\u2010LG and the key amino acids with positive charges in the target region of A29L, a key surface protein of MPXV. A synergistic effect was observed when 3HP\u2010\u03b2\u2010LG was combined with tecovirimat, a small\u2010molecule antiviral drug approved by the United States Food and Drug Administration and the European Medicine Agency for the treatment of smallpox and mpox. Because of its clinically proven safety and stability, 3HP\u2010\u03b2\u2010LG shows promise for further development as a prophylactic agent to prevent the sexual transmission of MPXV.<\/jats:p>","DOI":"10.1002\/mco2.677","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T04:48:10Z","timestamp":1722833290000},"source":"Crossref","is-referenced-by-count":4,"title":["A clinically used anti\u2010human papilloma virus agent (3\u2010hydroxyphthalic anhydride\u2010modified bovine \u03b2\u2010lactoglobulin) has a potential for topical application to prevent sexual transmission of monkeypox virus"],"prefix":"10.1002","volume":"5","author":[{"given":"Yi'ou","family":"Sha","sequence":"first","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC\/CAMS) Shanghai Institute of Infectious Disease and Biosecurity School of Basic Medical Sciences Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baoying","family":"Huang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID) NHC Key Laboratory of Biosafety National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and Prevention  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Hua","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC\/CAMS) Shanghai Institute of Infectious Disease and Biosecurity School of Basic Medical Sciences Fudan University  Shanghai China"},{"name":"Shanxi Key Laboratory of Functional Proteins, Fudan\u2010Jinbo Functional Protein Joint Research Center Shanxi Jinbo Bio\u2010Pharmaceutical Co. 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