Heat Treatment Promotes Ubiquitin-Mediated Proteolysis of SARS-CoV-2 RNA Polymerase and Decreases Viral Load  

作　　者：Yasen Maimaitiyiming Tao Yang Qian Qian Wang Yan Feng Zhi Chen Mikael Bjorklund Fudi Wang Chonggao Hu Chih-Hung Hsu Hua Naranmandura 

机构地区：[1]Deparment of Public Healh and Department of Hematology of First Afilated Hospital,Zhejiang Unvrsity Schoo of Medicine,Hangzhou 310058,China [2]Zhejiang University Cancer Cenler,Hangzhou 310058,China [3]Deparment of Neurobiology and Depariment of Neurology of the First Afiliated Hospital Zhejiang University School of Medicire.NHC and CAMS Key Laboratory of Medical Neurobiology,School of Brain Science and Brain Medicine,Zhejiang University,Hangzhou 310058,China [4]Zhejing Provincial Center for Disease Control and Prevention,Hangzhou 310051,China [5]State Key Laboratory for Diagrosis and Treatment of Infectious Diseases,Collaborative Innovation Center for DigHosis and Treatment of Infectious Disease,The First filiated Hospital,Zhejiang University School of Medicine,Hangzhou,China [6]Zhejing Unversity-Univrsity of Edinburgh(ZJU-UoE)Institute,Haining 314499,Zhejiang,China [7]The First Afiliated Hospital,Institute of Trarslational Medicine,Schoo of Public Health,Zhejiang University School of Medicine.Hangzhou 310058,Chima [8]Hengvang Medical School,University of South China,Hengvang 421001,China [9]Women's Hospital,Institut of Genctics,and Departmrent of Enwironmental Medicine.Zhejiang Universty School of Medicine,Hangzhou 310006,China

出　　处：《Research》2022年第2期41-45,共5页研究（英文）

基　　金：supported by grants from the Zhejiang Provincial Natural Science Foundation of China(LD22H310005);the National Science and Technology Major Project of the Ministry of Science and Technology of China(No.2018ZX10302-206);the National Key R&D Program of China(2021YFC2700903);the National Natural Science Foundation of China(Nos.81872942,82000155,82003875,and 31972883);the China Postdoctoral Science Foundation(No.2021M702877);and the Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents.

摘　　要：Despite extensive eforts,COVID-19 pandemic caused by the SARS-CoV-2 virus is still at large.Vaccination is an eftive approach to curb virus spread,but several variants(eg.delta,delta plus,omicron,and IHU)appear to weaken or possibly escape immune protection.Thus,novel and quickly scalable approaches to restrain SARS-CoV-2 are urgently needed.Mutiple evidences showed thermal sensitivity of SARS-CoV-2 and negative correlation between environmental temperature and COVID-19 transmission with unknown mechanism.Here.we reveal a potential mechanism by which mild heat treatment destabilizes the wild-type RNA-dependent RNA polymerase(also known a nonstructural protein 12(NSP12))of SARS-CoV-2 as well as the P323L mutant commonly found in SARS-CoV-2 variants,including omicron and IHU.Mechanistically,heat treatment promotes E3 ubiquitin ligase ZNF598-dependent NSP12 ubiquitination leading to proteasomal degradation and significantly decreases SARS-CoV-2 RNA copy number and viral titer.A mild daily heat Ireatment maintains low levels of both wild-type and P323L mutant of NSP12,sugesting clinical potential.Collctivel',this novel mechanism,heat-induced NSP12 degradation,suggests a prospective heat-based intervention against SARS-CoV-2.

关 键 词：NSP1 mechanism DELTA 

分 类 号：R563.1[医药卫生—呼吸系统]