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Supersaturation-driven self-assembly formation of ceftriaxone sodium spherulites:From amorphous form to spherulites

Particuology 2024年第7期90卷 10-19页

作者： Shankun Liang Yuchao Niu Xueyan Hu Wu Xiao Xuehua Ruan Gaohong He Xiaobin Jiang State Key Laboratory of Fine Chemicals Frontiers Science Center for Smart MaterialsSchool of Chemical EngineeringDalian University of TechnologyDalian116024China School of Chemical Engineering at Panjin Dalian University of TechnologyPanjin124221China

Drug particles with spherical morphology possess amazing advantages in terms of particle flowability,mechanical properties,drug solubility,and *** growth mechanism of drug spherulite is of great importance for the preparation and regulation of ***,ceftriaxone sodium spherulites were fabricated by the antisolvent crystallization method using dropwise addition of ceftriaxone sodium solution to *** observation of the whole crystallization process combined with electron microscopy technique revealed the spherical growth process from amorphous form to *** the supersaturation of the crystallization system was adjusted,the ceftriaxone sodium crystals transformed from amorphous form to *** the process of antisolvent crystallization with acetone as antisolvent,when the theoretical supersaturation degree S was higher than 2.62,the crystallization system tended to appear amorphous form;when S was between 2.57 and 2.62,the amorphous form transformed into clustered spherulites;when S was less than 2.57,the surface of spherulites will be covered with flaky crystal,which transformed into urchin-like *** the understanding of the spherical growth mechanism,the ceftriaxone sodium spherulites prepared in this research with modified supersaturation control had a low residue of antisolvent acetone,and the flowability was significantly improved.

关键词： Spherulite ceftriaxone sodium Antisolvent crystallization Supersaturation Online observation

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Antiviral drug design based on structural insights into the N-terminal domain and C-terminal domain of the SARS-CoV-2 nucleocapsid protein

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Science Bulletin 2022年第22期67卷 2327-2335页

作者： Xiaodong Luan Xinming Li Yufan Li Gengchen Su Wanchao Yin Yi Jiang Ning Xu Feng Wang Wang Cheng Ye Jin Leike Zhang H.Eric Xu Yi Xue Shuyang Zhang School of Medicine Tsinghua UniversityBeijing 100084China Department of Cardiology Peking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical SciencesBeijing 100730China Tsinghua-Peking Center for Life Sciences Tsinghua UniversityBeijing 100084China School of Life Science Tsinghua UniversityBeijing 100084China Beijing Advanced Innovation Center for Structural Biology Beijing 100084China The CAS Key Laboratory of Receptor Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of Chinese Academy of Sciences Beijing 100049China WuxiBiortus Biosciences Co. Ltd.Jiangyin 214437China State Key Laboratory of Virology Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan 430071China

Nucleocapsid(N) protein plays crucial roles in the life cycle of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), including the formation of ribonucleoprotein(RNP) complex with the viral *** we reported the crystal structures of the N-terminal domain(NTD) and C-terminal domain(CTD) of the N protein and an NTD-RNA complex. Our structures reveal a unique tetramer organization of NTD and identify a distinct RNA binding mode in the NTD-RNA complex, which could contribute to the formation of the RNP complex. We also screened small molecule inhibitors of N-NTD and N-CTD and discovered that ceftriaxone sodium, an antibiotic, can block the binding of RNA to NTD and inhibit the formation of the RNP complex. These results together could facilitate the further research of antiviral drug design targeting N protein.

关键词： SARS-CoV-2 Nucleocapsid protein N-terminal domain ceftriaxone sodium

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