Influenza is an acute respiratory infectious disease caused by the influenza virus,affecting people globally and causing significant social and economic losses.Due to the inevitable limitations of vaccines and approve...Influenza is an acute respiratory infectious disease caused by the influenza virus,affecting people globally and causing significant social and economic losses.Due to the inevitable limitations of vaccines and approved drugs,there is an urgent need to discover new anti-influenza drugs with different mechanisms.The viral ribonucleoprotein complex(vRNP)plays an essential role in the life cycle of influenza viruses,representing an attractive target for drug design.In recent years,the functional area of constituent proteins in vRNP are widely used as targets for drug discovery,especially the PA endonuclease active site,the RNA-binding site of PB1,the cap-binding site of PB2 and the nuclear export signal of NP protein.Encouragingly,the PA inhibitor baloxavir has been marketed in Japan and the United States,and several drug candidates have also entered clinical trials,such as favipiravir.This article reviews the compositions and functions of the influenza virus vRNP and the research progress on vRNP inhibitors,and discusses the representative drug discovery and optimization strategies pursued.展开更多
Influenza Avirus is one of the major pathogens that pose a large threat to human health worldwide and has caused pandemics.Influenza A virus is the Orthomyxoviridae prototype,and has 8 segmented negative-sense singles...Influenza Avirus is one of the major pathogens that pose a large threat to human health worldwide and has caused pandemics.Influenza A virus is the Orthomyxoviridae prototype,and has 8 segmented negative-sense singlestranded RNA(vRNA)as its genome.Influenza virus RNA polymerase(RdRp)consists of three subunits PB2,PB1 and PA,and catalyzes both transcription and replication.Recently,intensive biochemical and structural analysis of its RdRp has been performed.In this paper,we review the details from the biochemical analysis of the purified influenza virus RdRp and the classical ribonucleoprotein complex,as well as piece together their structures to form an overall picture.展开更多
基金Financial support from the National Natural Science Foundation of China (No.81773574, China)Science Foundation for Outstanding Young Scholars of Shandong Province (ZR2020JQ31, China)+9 种基金Foreign cultural and educational experts Project (GXL20200015001, China)Qilu Young Scholars Program of Shandong Universitythe Taishan Scholar Program at Shandong ProvinceShandong Province Key Research and Development Project (No.2019JZZY021011, China)Shandong Modern Agricultural Technology & Industry System (SDAIT-21-06 and SDAIT11-01)Agricultural scientific and technological innovation project of Shandong Academy of Agricultural Sciences (CXGC2021A12, China)Associazione Italiana per la Ricerca sul Cancro, AIRC, grant No.IG18855 (to Arianna Loregian, Italy)British Society for Antimicrobial Chemotherapy, UK, BSAC-2018-0064 (to Arianna Loregian, Italy)Ministero dell’Istruzione, dell’Università e della Ricerca, PRIN 2017-cod.2017KM79NN (to Arianna Loregian, Italy)Fondazione Cassa di Risparmio di Padova e Rovigo-Bando Ricerca COVID-2019 Nr.55777 2020.0162 (to Arianna Loregian, Italy)
文摘Influenza is an acute respiratory infectious disease caused by the influenza virus,affecting people globally and causing significant social and economic losses.Due to the inevitable limitations of vaccines and approved drugs,there is an urgent need to discover new anti-influenza drugs with different mechanisms.The viral ribonucleoprotein complex(vRNP)plays an essential role in the life cycle of influenza viruses,representing an attractive target for drug design.In recent years,the functional area of constituent proteins in vRNP are widely used as targets for drug discovery,especially the PA endonuclease active site,the RNA-binding site of PB1,the cap-binding site of PB2 and the nuclear export signal of NP protein.Encouragingly,the PA inhibitor baloxavir has been marketed in Japan and the United States,and several drug candidates have also entered clinical trials,such as favipiravir.This article reviews the compositions and functions of the influenza virus vRNP and the research progress on vRNP inhibitors,and discusses the representative drug discovery and optimization strategies pursued.
文摘Influenza Avirus is one of the major pathogens that pose a large threat to human health worldwide and has caused pandemics.Influenza A virus is the Orthomyxoviridae prototype,and has 8 segmented negative-sense singlestranded RNA(vRNA)as its genome.Influenza virus RNA polymerase(RdRp)consists of three subunits PB2,PB1 and PA,and catalyzes both transcription and replication.Recently,intensive biochemical and structural analysis of its RdRp has been performed.In this paper,we review the details from the biochemical analysis of the purified influenza virus RdRp and the classical ribonucleoprotein complex,as well as piece together their structures to form an overall picture.
