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Discovery of a Potent Botulinum Neurotoxin A Inhibitor ZM299 with Effective Protections in Botulism Mice 被引量:2
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作者 Jianxin Wang Yuelin Wu +11 位作者 deyan luo Chunlin Zhuang Nianzhi Ning Yanming Zhang Zhili He Jie Gao Zhanying Hong Xiguo Xv Wannian Zhang Tao Li Zhenyuan Miao Hui Wang 《Chinese Journal of Chemistry》 SCIE CAS CSCD 2022年第3期357-364,共8页
Botulinum neurotoxins serotype A(BoNT/A)is the deadliest toxins known to humans and the"Category A"agent for bioterrorism.Over the past 20 years,significant efforts have been put forth to develop effective i... Botulinum neurotoxins serotype A(BoNT/A)is the deadliest toxins known to humans and the"Category A"agent for bioterrorism.Over the past 20 years,significant efforts have been put forth to develop effective inhibitors of BoNT/A.Unfortunately,few identified inhibitors possess noteworthy efficacy against BoNT/A in vivo.Here,we performed a high-throughput virtual screening based on the structure-based docking simulations and found a novel potent scaffold 2-thionicotinate that inhibits the BoNT/A light chain(LC).We then synthesized and optimized a novel series of 2-thionicotinate derivatives and comprehensively evaluated their activity against BoNT/A in vitro and in vivo.An optimized compound ZM299 effectively exhibits anti-BoNT/A activity in primary neurons and displayed remarkably therapeutic efficacy against BoNT/A in vivo,which could raise the survival rate of intoxicated mice to 100%(12/12)after lethal doses of BoNT/A exposures.These findings demonstrate that 2-thionicotinates is a promising scaffold for producing more effective anti-BoNT/A analogs,and compound ZM299 is worthy of further preclinical evaluation as a drug candidate for the treatment of botulism. 展开更多
关键词 Botulinum Neurotoxin A BOTULISM Virtual screening Drug design INHIBITORS
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An updated RBD-Fc fusion vaccine booster increases neutralization of SARS-CoV-2 Omicron variants
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作者 deyan luo Xiaolan Yang +7 位作者 Tao Li Nianzhi Ning Song Jin Zhuangzhuang Shi Hongjing Gu Deyu Li Yuwei Gao Hui Wang 《Signal Transduction and Targeted Therapy》 SCIE CSCD 2022年第10期3652-3654,共3页
Dear Editor,Coronavirus disease 2019(COVID-19)is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which is a novel subset of coronavirus.To this day,the number of confirmed cases is over 500 milli... Dear Editor,Coronavirus disease 2019(COVID-19)is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which is a novel subset of coronavirus.To this day,the number of confirmed cases is over 500 million with more than 6 million deaths globally.SARSCoV-2 keeps on evolving into different variants,including Alpha,Beta,Gamma,Delta,and Omicron. 展开更多
关键词 acute RESPIRATORY vaccine
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