Genome-wide association analysis allows the identification of potential candidate genes involved in the development of severe coronavirus disease 2019(COVID-19).Hence,it seems that genetics matters here,as well.Nevert...Genome-wide association analysis allows the identification of potential candidate genes involved in the development of severe coronavirus disease 2019(COVID-19).Hence,it seems that genetics matters here,as well.Nevertheless,the virus's nature,including its RNA structure,determines the rate of mutations leading to new viral strains with all epidemiological and clinical consequences.Given these observations,we herein comment on the current hypotheses about the possible role of the genes in association with COVID-19 severity.We discuss some of the major candidate genes that have been identified as potential genetic factors associated with the COVID-19 severity and infection susceptibility:HLA,ABO,ACE2,TLR7,ApoE,TYK2,OAS,DPP9,IFNAR2,CCR2,etc.Further study of genes and genetic variants will be of great benefit for the prevention and assessment of the individual risk and disease severity in different populations.These scientific data will serve as a basis for the development of clinically applicable diagnostic and prognostic tests for patients at high risk of COVID-19.展开更多
Dipeptidyl peptidase 4(DPP4)is recognised as an attractive anti-diabetic drug target,and several DPP4 inhibitors are already on the market.As members of the same gene family,dipeptidyl peptidase 8(DPP8)and dipeptidyl ...Dipeptidyl peptidase 4(DPP4)is recognised as an attractive anti-diabetic drug target,and several DPP4 inhibitors are already on the market.As members of the same gene family,dipeptidyl peptidase 8(DPP8)and dipeptidyl peptidase 9(DPP9)share high sequence and structural homology as well as functional activity with DPP4.However,the inhibition of their activities was reported to cause severe toxicities.Thus,the development of DPP4 inhibitors that do not have DPP8 and DPP9 inhibitory activity is critical for safe anti-diabetic therapy.To achieve this goal,we established a selective evaluation method for DPP4 inhibitors based on recombinant human DPP8 and DPP9 proteins expressed by Rosetta cells.In this method,we used purified recombinant 120 kDa DPP8 or DPP9 protein from the Rosetta expression system.The optimum concentrations of the recombinant DPP8 and DPP9 proteins were 30 ng/mL and 20 ng/mL,respectively,and the corresponding concentrations of their substrates were both 0.2 mmol/L.This method was highly reproducible and reliable for the evaluation of the DPP8 and DPP9 selectivity for DPP4 inhibitor candidates,which would provide valuable guidance in the development of safe DPP4 inhibitors.展开更多
文摘Genome-wide association analysis allows the identification of potential candidate genes involved in the development of severe coronavirus disease 2019(COVID-19).Hence,it seems that genetics matters here,as well.Nevertheless,the virus's nature,including its RNA structure,determines the rate of mutations leading to new viral strains with all epidemiological and clinical consequences.Given these observations,we herein comment on the current hypotheses about the possible role of the genes in association with COVID-19 severity.We discuss some of the major candidate genes that have been identified as potential genetic factors associated with the COVID-19 severity and infection susceptibility:HLA,ABO,ACE2,TLR7,ApoE,TYK2,OAS,DPP9,IFNAR2,CCR2,etc.Further study of genes and genetic variants will be of great benefit for the prevention and assessment of the individual risk and disease severity in different populations.These scientific data will serve as a basis for the development of clinically applicable diagnostic and prognostic tests for patients at high risk of COVID-19.
基金We greatly appreciate Prof.Haihong Huang and Dr.Bei Han for the chemical synthesis of UAMC00132sitagliptin.This work was supported by a fund from National Mega-project for Innova-tive Drugs(2012ZX09301002-004,China).
文摘Dipeptidyl peptidase 4(DPP4)is recognised as an attractive anti-diabetic drug target,and several DPP4 inhibitors are already on the market.As members of the same gene family,dipeptidyl peptidase 8(DPP8)and dipeptidyl peptidase 9(DPP9)share high sequence and structural homology as well as functional activity with DPP4.However,the inhibition of their activities was reported to cause severe toxicities.Thus,the development of DPP4 inhibitors that do not have DPP8 and DPP9 inhibitory activity is critical for safe anti-diabetic therapy.To achieve this goal,we established a selective evaluation method for DPP4 inhibitors based on recombinant human DPP8 and DPP9 proteins expressed by Rosetta cells.In this method,we used purified recombinant 120 kDa DPP8 or DPP9 protein from the Rosetta expression system.The optimum concentrations of the recombinant DPP8 and DPP9 proteins were 30 ng/mL and 20 ng/mL,respectively,and the corresponding concentrations of their substrates were both 0.2 mmol/L.This method was highly reproducible and reliable for the evaluation of the DPP8 and DPP9 selectivity for DPP4 inhibitor candidates,which would provide valuable guidance in the development of safe DPP4 inhibitors.
