Dear Editor,Tremendous efforts have been made globally to develop therapeutics and prophylactics against severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)which has caused thousands of millions of infections ...Dear Editor,Tremendous efforts have been made globally to develop therapeutics and prophylactics against severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)which has caused thousands of millions of infections and deaths worldwide.A series of potent neutralizing antibodies with defined epitopes targeting RBD have been recently identified with different strategies.However,being an RNA virus,the instability of the SARS-CoV-2 genome results in numerous S-protein variants with altered viral phenotypes.展开更多
As one of the most successful therapeutic target families,G protein-coupled receptors(GPCRs)have experienced a transformation from random ligand screening to knowledge-driven drug design.We are eye-witnessing tremendo...As one of the most successful therapeutic target families,G protein-coupled receptors(GPCRs)have experienced a transformation from random ligand screening to knowledge-driven drug design.We are eye-witnessing tremendous progresses made recently in the understanding of their structure-function relationships that facilitated drug development at an unprecedented pace.This article intends to provide a comprehensive overview of this important field to a broader readership that shares some common interests in drug discovery.展开更多
Olfactory receptors are poorly annotated for most genome-sequenced chordates.To address this deficiency,we developed a nhmmer-based olfactory receptor annotation tool Genome2OR(https://github.com/To Hanwei/Genome2OR.g...Olfactory receptors are poorly annotated for most genome-sequenced chordates.To address this deficiency,we developed a nhmmer-based olfactory receptor annotation tool Genome2OR(https://github.com/To Hanwei/Genome2OR.git),and used it to process 1,695 sequenced chordate genomes in the NCBI Assembly database as of January,2021.In total,765,248 olfactory receptor genes were annotated,with 404,426 functional genes and 360,822 pseudogenes,which represents a four-fold increase in the number of annotated olfactory receptors.Based on the annotation data,we built a database called Chordata Olfactory Receptor Database(CORD,https://cord.ihuman.shanghaitech.edu.cn)for archiving,analysing and disseminating the data.Beyond the primary data,we offer derivative information,including pictures of species,cross references to public databases,structural models,sequence similarity networks and sequence profiles in the CORD.Furthermore,we did brief analyses on these receptors,including building a huge protein sequence similarity network covering all receptors in the database,and clustering them into 20 communities,classifying the 20 communities into three categories based on their presences/absences in ray-finned fish and/or lobe-finned fish.We infer that olfactory receptors should have unique activation and desensitization mechanisms by analysing their sequences and structural models.We believe the CORD can benefit the researchers and the general public who are interested in olfaction.展开更多
基金supported by ShanghaiTech,Shanghai Frontiers Science Center for Biomacromolecules and Precision Medicine at ShanghaiTech University(G.Z.),and grants from the National Key Research and Development Program of China[Grant Nos.2017YFC1001301(G.Z.),2019YFA0111001(H.W.)]the National Natural Science Foundation of China[Nos.31670919(H.W.),81822045(L.L.)]+1 种基金Lingang Laboratory(No.LG202101-01-07 to X.Y.),Program of Shanghai Academic/Technology Research Leader[20XD1420300(L.L.)]Emergency response to new coronavirus infection scientific and technological project[YD9110002004(J.W.)],and Shanghai Sailing Program[20YF1430900(S.-M.Z.)].
文摘Dear Editor,Tremendous efforts have been made globally to develop therapeutics and prophylactics against severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)which has caused thousands of millions of infections and deaths worldwide.A series of potent neutralizing antibodies with defined epitopes targeting RBD have been recently identified with different strategies.However,being an RNA virus,the instability of the SARS-CoV-2 genome results in numerous S-protein variants with altered viral phenotypes.
基金The authors acknowledge funding support from the National Natural Science Foundation of China 81872915(to M.-W.W.),81773792(to D.Y.),81973373(to D.Y.),21704064(to Q.Z.),31971362(to W.S.),31971178(to S.Z.),and 31770796(to Y.J.)National Science&Technology Major Project of China-Key New Drug Creation and Manufacturing Program 2018ZX09735-001(to M.-W.W.),2018ZX09711002-002-005(to D.Y.),and 2018ZX09711002-002-002(to Y.J.)+4 种基金the National Key Basic Research Program of China 2018YFA0507000(to M.-W.W.,S.Z.,W.S.,and H.T.)Novo Nordisk-CAS Research Fund grant NNCAS-2017-1-CC(to D.Y.)The Belt and Road Master Fellowship program(to V.L.)UCAS Scholarship for International Students(to S.D.)and The CAS-TWAS President's Fellowship for International Doctoral Students(to E.Y.).
文摘As one of the most successful therapeutic target families,G protein-coupled receptors(GPCRs)have experienced a transformation from random ligand screening to knowledge-driven drug design.We are eye-witnessing tremendous progresses made recently in the understanding of their structure-function relationships that facilitated drug development at an unprecedented pace.This article intends to provide a comprehensive overview of this important field to a broader readership that shares some common interests in drug discovery.
基金supported by the National Natural Science Foundation of China(32122024,31971178)the National Key Research and Development Programs of China(2018YFA0507000)ShanghaiTech University。
文摘Olfactory receptors are poorly annotated for most genome-sequenced chordates.To address this deficiency,we developed a nhmmer-based olfactory receptor annotation tool Genome2OR(https://github.com/To Hanwei/Genome2OR.git),and used it to process 1,695 sequenced chordate genomes in the NCBI Assembly database as of January,2021.In total,765,248 olfactory receptor genes were annotated,with 404,426 functional genes and 360,822 pseudogenes,which represents a four-fold increase in the number of annotated olfactory receptors.Based on the annotation data,we built a database called Chordata Olfactory Receptor Database(CORD,https://cord.ihuman.shanghaitech.edu.cn)for archiving,analysing and disseminating the data.Beyond the primary data,we offer derivative information,including pictures of species,cross references to public databases,structural models,sequence similarity networks and sequence profiles in the CORD.Furthermore,we did brief analyses on these receptors,including building a huge protein sequence similarity network covering all receptors in the database,and clustering them into 20 communities,classifying the 20 communities into three categories based on their presences/absences in ray-finned fish and/or lobe-finned fish.We infer that olfactory receptors should have unique activation and desensitization mechanisms by analysing their sequences and structural models.We believe the CORD can benefit the researchers and the general public who are interested in olfaction.
