A protease activity profiling strategy to inhibit cell-to-cell transmission of SARS-CoV-2

抑制 SARS-CoV-2 细胞间传播的蛋白酶活性分析策略

• 批准号: MC_PC_19063
• 负责人: Sumana Sanyal
• 金额: $ 27.16万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_PC_19063
• 关键词: protease; activity; profiling; strategy; inhibit

SARS-CoV-2 is a new coronavirus, which emerged in late 2019, has infected tens of thousands in China, and has now spread into 40 countries. To break the chain of transmission, host and viral determinants that increase the transmissability of SARS-CoV-2 need to be identified, in order to develope suitable and effective intervnetions. Two main determinants of virus transmission are the host cellular proteases that cleave the viral Spike protein to make it more infectious, and the viral Spiek itself that has evolved to carry additional protease-cleavage sites, allowing host expansion. We aim to identify these cellular proteases and inhibit them to block virus transmission. We also aim to generate virus with Spike proteins that cannot be cleaved, to determine whether we can arrest their spread. Collectively these approaches will be used to inform production of therapeutic molecules (against the proteases) and design of vaccines (against the viral Spike).

SARS-CoV-2是一种新型冠状病毒，于2019年底出现，已在中国感染了数万人，目前已蔓延到40个国家。为了打破传播链，需要确定增加SARS-CoV-2传播能力的宿主和病毒决定因素，以便开发合适和有效的干预措施。病毒传播的两个主要决定因素是宿主细胞蛋白酶，其切割病毒刺突蛋白以使其更具感染性，以及病毒刺突本身，其已经进化为携带额外的蛋白酶切割位点，从而允许宿主扩增。我们的目标是识别这些细胞蛋白酶并抑制它们以阻断病毒传播。我们的目标还在于产生具有不能被切割的刺突蛋白的病毒，以确定我们是否可以阻止它们的传播。总的来说，这些方法将用于指导治疗分子（针对蛋白酶）的生产和疫苗（针对病毒刺突）的设计。

项目成果

How SARS-CoV-2 (COVID-19) spreads within infected hosts - what we know so far.

• DOI: 10.1042/etls20200165
• 发表时间: 2020-12-11
• 期刊: Emerging topics in life sciences
• 影响因子: 3.8
• 作者: Sanyal S

ISG15 driven cellular responses to virus infection.

• DOI: 10.1042/bst20220839
• 发表时间: 2022-12-16
• 期刊: Biochemical Society transactions
• 影响因子: 3.9

Ring finger protein 213 assembles into a sensor for ISGylated proteins with antimicrobial activity.

• DOI: 10.1038/s41467-021-26061-w
• 发表时间: 2021-10-01
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Thery F;Martina L;Asselman C;Zhang Y;Vessely M;Repo H;Sedeyn K;Moschonas GD;Bredow C;Teo QW;Zhang J;Leandro K;Eggermont D;De Sutter D;Boucher K;Hochepied T;Festjens N;Callewaert N;Saelens X;Dermaut B;Knobeloch KP;Beling A;Sanyal S;Radoshevich L;Eyckerman S;Impens F
• 通讯作者: Impens F

Viral inhibition of ER-phagy is critical to membrane remodelling for biogenesis of (+)RNA virus replication organelles

病毒对 ER 吞噬的抑制对于 ( )RNA 病毒复制细胞器生物发生的膜重塑至关重要

• DOI: 10.21203/rs.3.rs-2074952/v1
• 发表时间: 2022
• 作者: Sanyal S

Pathogenesis and virulence of flavivirus infections.

• DOI: 10.1080/21505594.2021.1996059
• 发表时间: 2021-12
• 期刊: Virulence
• 影响因子: 5.2
• 作者: van Leur SW;Heunis T;Munnur D;Sanyal S
• 通讯作者: Sanyal S