Title:
METHOD FOR OPTIMIZING VIRUS MEMBRANE FUSION INHIBITOR, BROAD-SPECTRUM ANTI-CORONAVIRUS LIPOPEPTIDE AND USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2023/155318
Kind Code:
A1
Abstract:
Provided are a broad-spectrum anti-SARS-CoV-2 lipopeptide, a preparation method therefor, a virus membrane fusion inhibitor comprising the lipopeptide, and use of the lipopeptide in the preparation of a pharmaceutical composition for preventing and treating diseases caused by the coronavirus. The structure of the lipopeptide is shown as formula (I) or formula (II), wherein X1 is an amino protection group; X2 is a polypeptide, whose amino acid sequence is (EAAAK)n or A[(EAAAK)n]A, wherein n is a natural number less than 5 and indicates the number of repetitions of the EAAAK sequence; X3 is lysine or cysteine or 2,3-diaminopropionic acid or ornithine or 2,4-diaminobutanoic acid or 2,7-diaminoheptanoic acid; X4 is a lipophilic compound group; X5 is a carboxy-terminal protecting group.
Inventors:
HE YUXIAN (CN)
ZHU YUANMEI (CN)
CHONG HUIHUI (CN)
LIU NIAN (CN)
ZHU YUANMEI (CN)
CHONG HUIHUI (CN)
LIU NIAN (CN)
Application Number:
PCT/CN2022/094001
Publication Date:
August 24, 2023
Filing Date:
May 19, 2022
Export Citation:
Assignee:
YOUCARE PHARMACEUTICAL GROUP (CN)
International Classes:
C07K14/00; A61K38/16; A61K47/64; A61P31/14; C07K1/107; C07K19/00
Foreign References:
| CN112625094A | 2021-04-09 | |||
| CN111643656A | 2020-09-11 | |||
| CN111675752A | 2020-09-18 |
Other References:
YU DANWEI, ZHU YUANMEI, JIAO TAO, WU TONG, XIAO XIA, QIN BO, CHONG HUIHUI, LEI XIAOBO, REN LILI, CUI SHENG, WANG JIANWEI, HE YUXIA: "Structure-based design and characterization of novel fusion-inhibitory lipopeptides against SARS-CoV-2 and emerging variants", EMERGING MICROBES & INFECTIONS, vol. 10, no. 1, 1 January 2021 (2021-01-01), pages 1227 - 1240, XP093086296, DOI: 10.1080/22221751.2021.1937329
"Linkers in biomacromolecules", vol. 647, 21 January 2021, ISBN: 978-0-12-820818-2, article RYOICHI ARAI: "Design of Helical Linkers for Fusion Proteins and Protein-Based Nanostructures", pages: 209 - 230, XP009548593, DOI: 10.1016/bs.mie.2020.10.003
ZHU YUANMEI, YU DANWEI, HU YUE, WU TONG, CHONG HUIHUI, HE YUXIAN: "SARS-CoV-2-derived fusion inhibitor lipopeptides exhibit highly potent and broad-spectrum activity against divergent human coronaviruses", SIGNAL TRANSDUCTION AND TARGETED THERAPY, vol. 6, no. 1, XP093086300, DOI: 10.1038/s41392-021-00698-x
YU DANWEI, ZHU YUANMEI, YAN HONGXIA, WU TONG, CHONG HUIHUI, HE YUXIAN: "Pan-coronavirus fusion inhibitors possess potent inhibitory activity against HIV-1, HIV-2, and simian immunodeficiency virus", EMERGING MICROBES & INFECTIONS, vol. 10, no. 1, 1 January 2021 (2021-01-01), pages 810 - 821, XP093086302, DOI: 10.1080/22221751.2021.1917309
ZHU YUANMEI, YU DANWEI, YAN HONGXIA, CHONG HUIHUI, HE YUXIAN: "Design of Potent Membrane Fusion Inhibitors against SARS-CoV-2, an Emerging Coronavirus with High Fusogenic Activity", JOURNAL OF VIROLOGY, AMERICAN SOCIETY FOR MICROBIOLOGY, 1 July 2021 (2021-07-01), pages 1 - 12, XP093045558, Retrieved from the Internet [retrieved on 20230510], DOI: 10.1128/JVI
ZHOU JIE, XU WEI, LIU ZEZHONG, WANG CHAO, XIA SHUAI, LAN QIAOSHUAI, CAI YANXING, SU SHAN, PU JING, XING LIXIAO, XIE YOUHUA, LU LU,: "A highly potent and stable pan-coronavirus fusion inhibitor as a candidate prophylactic and therapeutic for COVID-19 and other coronavirus diseases", ACTA PHARMACEUTICA SINICA B, vol. 12, no. 4, 1 April 2022 (2022-04-01), pages 1652 - 1661, XP093086307, ISSN: 2211-3835, DOI: 10.1016/j.apsb.2021.07.026
XIA SHUAI; LIU MEIQIN; WANG CHAO; XU WEI; LAN QIAOSHUAI; FENG SILIANG; QI FEIFEI; BAO LINLIN; DU LANYING; LIU SHUWEN; QIN CHUAN; S: "Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion", CELL RESEARCH, SPRINGER SINGAPORE, SINGAPORE, vol. 30, no. 4, 30 March 2020 (2020-03-30), Singapore , pages 343 - 355, XP037082964, ISSN: 1001-0602, DOI: 10.1038/s41422-020-0305-x
DE VRIES RORY D., SCHMITZ KATHARINA S., BOVIER FRANCESCA T., PREDELLA CAMILLA, KHAO JONATHAN, NOACK DANNY, HAAGMANS BART L., HERFS: "Intranasal fusion inhibitory lipopeptide prevents direct-contact SARS-CoV-2 transmission in ferrets", SCIENCE, AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE, US, vol. 371, no. 6536, 26 March 2021 (2021-03-26), US , pages 1379 - 1382, XP093086309, ISSN: 0036-8075, DOI: 10.1126/science.abf4896
"Linkers in biomacromolecules", vol. 647, 21 January 2021, ISBN: 978-0-12-820818-2, article RYOICHI ARAI: "Design of Helical Linkers for Fusion Proteins and Protein-Based Nanostructures", pages: 209 - 230, XP009548593, DOI: 10.1016/bs.mie.2020.10.003
ZHU YUANMEI, YU DANWEI, HU YUE, WU TONG, CHONG HUIHUI, HE YUXIAN: "SARS-CoV-2-derived fusion inhibitor lipopeptides exhibit highly potent and broad-spectrum activity against divergent human coronaviruses", SIGNAL TRANSDUCTION AND TARGETED THERAPY, vol. 6, no. 1, XP093086300, DOI: 10.1038/s41392-021-00698-x
YU DANWEI, ZHU YUANMEI, YAN HONGXIA, WU TONG, CHONG HUIHUI, HE YUXIAN: "Pan-coronavirus fusion inhibitors possess potent inhibitory activity against HIV-1, HIV-2, and simian immunodeficiency virus", EMERGING MICROBES & INFECTIONS, vol. 10, no. 1, 1 January 2021 (2021-01-01), pages 810 - 821, XP093086302, DOI: 10.1080/22221751.2021.1917309
ZHU YUANMEI, YU DANWEI, YAN HONGXIA, CHONG HUIHUI, HE YUXIAN: "Design of Potent Membrane Fusion Inhibitors against SARS-CoV-2, an Emerging Coronavirus with High Fusogenic Activity", JOURNAL OF VIROLOGY, AMERICAN SOCIETY FOR MICROBIOLOGY, 1 July 2021 (2021-07-01), pages 1 - 12, XP093045558, Retrieved from the Internet
ZHOU JIE, XU WEI, LIU ZEZHONG, WANG CHAO, XIA SHUAI, LAN QIAOSHUAI, CAI YANXING, SU SHAN, PU JING, XING LIXIAO, XIE YOUHUA, LU LU,: "A highly potent and stable pan-coronavirus fusion inhibitor as a candidate prophylactic and therapeutic for COVID-19 and other coronavirus diseases", ACTA PHARMACEUTICA SINICA B, vol. 12, no. 4, 1 April 2022 (2022-04-01), pages 1652 - 1661, XP093086307, ISSN: 2211-3835, DOI: 10.1016/j.apsb.2021.07.026
XIA SHUAI; LIU MEIQIN; WANG CHAO; XU WEI; LAN QIAOSHUAI; FENG SILIANG; QI FEIFEI; BAO LINLIN; DU LANYING; LIU SHUWEN; QIN CHUAN; S: "Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion", CELL RESEARCH, SPRINGER SINGAPORE, SINGAPORE, vol. 30, no. 4, 30 March 2020 (2020-03-30), Singapore , pages 343 - 355, XP037082964, ISSN: 1001-0602, DOI: 10.1038/s41422-020-0305-x
DE VRIES RORY D., SCHMITZ KATHARINA S., BOVIER FRANCESCA T., PREDELLA CAMILLA, KHAO JONATHAN, NOACK DANNY, HAAGMANS BART L., HERFS: "Intranasal fusion inhibitory lipopeptide prevents direct-contact SARS-CoV-2 transmission in ferrets", SCIENCE, AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE, US, vol. 371, no. 6536, 26 March 2021 (2021-03-26), US , pages 1379 - 1382, XP093086309, ISSN: 0036-8075, DOI: 10.1126/science.abf4896
Attorney, Agent or Firm:
MERITS IP LTD. (CN)
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