A clinically used anti‐human papilloma virus agent (3‐hydroxyphthalic anhydride‐modified bovine β‐lactoglobulin) has a potential for topical application to prevent sexual transmission of monkeypox virus
Yi'ou Sha,
Baoying Huang,
Chen Hua,
Yun Zhu,
Wanbo Tai,
Jiewei Sun,
Yixin Li,
Anqi Xia,
Qiao Wang,
Lu Lu,
Wenjie Tan,
Shibo Jiang
Affiliations
Yi'ou Sha
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
Baoying Huang
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
Chen Hua
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
Yun Zhu
National Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing China
Wanbo Tai
Institute of Infectious Diseases Shenzhen Bay Laboratory Shenzhen China
Jiewei Sun
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
Yixin Li
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
Anqi Xia
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
Qiao Wang
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
Lu Lu
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
Wenjie Tan
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
Shibo Jiang
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
Abstract A global outbreak of monkeypox (mpox) caused by the mpox virus (MPXV) has posed a serious threat to public health worldwide, thus calling for the urgent development of antivirals and vaccines to curb its further spread. In this study, we screened 41 anhydride‐modified proteins and found that 3‐hydroxyphthalic anhydride‐modified β‐lactoglobulin (3HP‐β‐LG), a clinically used anti‐HPV agent, was highly effective in inhibiting infection of vaccinia virus Tiantan strain (VACV‐VTT) and MPXV. Mechanistic studies demonstrated that 3HP‐β‐LG 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‐β‐LG 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‐β‐LG was combined with tecovirimat, a small‐molecule 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‐β‐LG shows promise for further development as a prophylactic agent to prevent the sexual transmission of MPXV.