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Sökning: WFRF:(Li Jianghong) > (2018) > Discovery of Highly...

Discovery of Highly Potent Pinanamine-Based Inhibitors against Amantadine- and Oseltamivir-Resistant Influenza A Viruses

Zhao, Xin (författare)
Guangzhou Med Univ, Sch Pharmaceut Sci, Key Lab Mol Target & Clin Pharmacol, State Key Lab Resp Dis, Guangzhou 511436, Guangdong, Peoples R China.;Guangzhou Med Univ, Affiliated Hosp 5, Guangzhou 511436, Guangdong, Peoples R China.;Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou 510530, Guangdong, Peoples R China.;Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA.
Li, Runfeng (författare)
Guangzhou Med Univ, Guangzhou Inst Resp Hlth, Affiliated Hosp 1, Natl Clin Res Ctr Resp Dis,State Key Lab Resp Dis, Guangzhou 510120, Guangdong, Peoples R China.
Zhou, Yang (författare)
AlbaNova Univ Ctr, Royal Inst Technol KTH, Sch Biotechnol, Div Theoret Chem & Biol, SE-10044 Stockholm, Sweden.
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Xiao, Mengjie (författare)
Guangzhou Med Univ, Sch Pharmaceut Sci, Key Lab Mol Target & Clin Pharmacol, State Key Lab Resp Dis, Guangzhou 511436, Guangdong, Peoples R China.;Guangzhou Med Univ, Affiliated Hosp 5, Guangzhou 511436, Guangdong, Peoples R China.;Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou 510530, Guangdong, Peoples R China.
Ma, Chunlong (författare)
Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA.;Univ Arizona, BIO5 Inst, Tucson, AZ 85721 USA.
Yang, Zhongjin (författare)
Guangzhou Med Univ, Sch Pharmaceut Sci, Key Lab Mol Target & Clin Pharmacol, State Key Lab Resp Dis, Guangzhou 511436, Guangdong, Peoples R China.;Guangzhou Med Univ, Affiliated Hosp 5, Guangzhou 511436, Guangdong, Peoples R China.
Zeng, Shaogao (författare)
Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou 510530, Guangdong, Peoples R China.
Du, Qiuling (författare)
Guangzhou Med Univ, Guangzhou Inst Resp Hlth, Affiliated Hosp 1, Natl Clin Res Ctr Resp Dis,State Key Lab Resp Dis, Guangzhou 510120, Guangdong, Peoples R China.
Yang, Chunguang (författare)
Guangzhou Med Univ, Guangzhou Inst Resp Hlth, Affiliated Hosp 1, Natl Clin Res Ctr Resp Dis,State Key Lab Resp Dis, Guangzhou 510120, Guangdong, Peoples R China.
Jiang, Haiming (författare)
Guangzhou Med Univ, Guangzhou Inst Resp Hlth, Affiliated Hosp 1, Natl Clin Res Ctr Resp Dis,State Key Lab Resp Dis, Guangzhou 510120, Guangdong, Peoples R China.
Hu, Yanmei (författare)
Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA.;Univ Arizona, BIO5 Inst, Tucson, AZ 85721 USA.
Wang, Kefeng (författare)
Guangzhou Med Univ, Sch Pharmaceut Sci, Key Lab Mol Target & Clin Pharmacol, State Key Lab Resp Dis, Guangzhou 511436, Guangdong, Peoples R China.;Guangzhou Med Univ, Affiliated Hosp 5, Guangzhou 511436, Guangdong, Peoples R China.
Mok, Chris Ka Pun (författare)
Guangzhou Med Univ, Guangzhou Inst Resp Hlth, Affiliated Hosp 1, Natl Clin Res Ctr Resp Dis,State Key Lab Resp Dis, Guangzhou 510120, Guangdong, Peoples R China.;Univ Hong Kong, HKU Li Ka Shing Fac Med, Sch Publ Hlth, HKU Pasteur Res Pole, 5 Sassoon Rd, Hong Kong, Peoples R China.
Sun, Ping (författare)
Guangzhou Med Univ, Sch Pharmaceut Sci, Key Lab Mol Target & Clin Pharmacol, State Key Lab Resp Dis, Guangzhou 511436, Guangdong, Peoples R China.;Guangzhou Med Univ, Affiliated Hosp 5, Guangzhou 511436, Guangdong, Peoples R China.
Dong, Jianghong (författare)
Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou 510530, Guangdong, Peoples R China.
Cui, Wei (författare)
Wang, Jun (författare)
Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA.;Univ Arizona, BIO5 Inst, Tucson, AZ 85721 USA.
Tu, Yaoquan (författare)
KTH,Teoretisk kemi och biologi
Yang, Zifeng (författare)
Guangzhou Med Univ, Guangzhou Inst Resp Hlth, Affiliated Hosp 1, Natl Clin Res Ctr Resp Dis,State Key Lab Resp Dis, Guangzhou 510120, Guangdong, Peoples R China.
Hu, Wenhui (författare)
Guangzhou Med Univ, Sch Pharmaceut Sci, Key Lab Mol Target & Clin Pharmacol, State Key Lab Resp Dis, Guangzhou 511436, Guangdong, Peoples R China.;Guangzhou Med Univ, Affiliated Hosp 5, Guangzhou 511436, Guangdong, Peoples R China.;Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou 510530, Guangdong, Peoples R China.
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Guangzhou Med Univ, Sch Pharmaceut Sci, Key Lab Mol Target & Clin Pharmacol, State Key Lab Resp Dis, Guangzhou 511436, Guangdong, Peoples R China;Guangzhou Med Univ, Affiliated Hosp 5, Guangzhou 511436, Guangdong, Peoples R China.;Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou 510530, Guangdong, Peoples R China.;Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA. Guangzhou Med Univ, Guangzhou Inst Resp Hlth, Affiliated Hosp 1, Natl Clin Res Ctr Resp Dis,State Key Lab Resp Dis, Guangzhou 510120, Guangdong, Peoples R China. (creator_code:org_t)
2018-05-25
2018
Engelska.
Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 61:12, s. 5187-5198
Relaterad länk:
https://europepmc.or...
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https://urn.kb.se/re...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Influenza pandemic is a constant major threat to public health caused by influenza A viruses (IAVs). IAVs are subcategorized by the surface proteins hemagglutinin (HA) and neuraminidase (NA), in which they are both essential targets for drug discovery. While it is of great concern that NA inhibitor oseltamivir resistant strains are frequently identified from human or avian influenza virus, structural and functional characterization of influenza HA has raised hopes for new antiviral therapies. In this study, we explored a structure-activity relationship (SAR) of pinanamine-based antivirals and discovered a potent inhibitor M090 against amantadine-resistant viruses, including the 2009 H1N1 pandemic strains, and oseltamivir-resistant viruses. Mechanism of action studies, particularly hemolysis inhibition, indicated that M090 targets influenza HA and it occupied a highly conserved pocket of the HA(2) domain and inhibited virus-mediated membrane fusion by "locking" the bending state of HA(2) during the conformational rearrangement process. This work provides new binding sites within the HA protein and indicates that this pocket may be a promising target for broad-spectrum anti-influenza A drug design and development.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

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