Proteomics research reveals new therapeutic targets for new coronary pneumonia

On May 14, 2020, researchers from the University of Frankfurt and Goethe University published their latest research on SARS-CoV-2 infection characteristics and potential therapeutic targets for COVID-19 in the top journal NatureThe researchers found that SARS-CoV-2 reshaped central cell pathways during infection, including translation, splicing, carbon metabolism and nucleic acid metabolism, and that small molecular inhibitors targeting these pathways can inhibit the virus from replicating in cellshttps://doi.org/10.1038/s41586-020-2332-7researchers used the human colon epithelial cancer cell line Caco-2 to build a cell culture model infected with SARS-CoV-2By detecting Caco-2 infected with SARS-CoV-2, cell disease-causing effects occur after 24 hours, and within 24 hours the RNA copy of the virus in the upper liquid continues to increase, the virus nucleoprotein can also be stained, indicating that the cell culture model can be used to study different processes of the life cycle of SARS-CoV-2 infected cellsa replication model of SARS-CoV-2 in cells
in order to characterize SARS-CoV-2 infection, the researchers used the multiple-enhanced protein dynamics (mePROD) method to analyze protein differences in Caco-2 cells infected with SARS-CoV-2 and cultured for 2-14 hoursIt was found that, unlike other viruses that inhibitthe host protein synthesis and thus increase the synthesis of viral proteins, SARS-CoV-2 had only a slight effect on host translation capabilities, so the researchers speculated that SARS-CoV-2 replication may be sensitive to translation suppressionIt tested two translation inhibitors, cyclohemylamine (translation extension inhibitor) and qumetin (inhibited 40S ribosome protein S14), and found that they significantly inhibited SARS-CoV-2 replication at non-toxic concentrationschanges in host cell translation after SARS-CoV-2 infection
the researchers analyzed changes in host proteomics after cell infection virus, and found that the host proteomics were widely regulated 24 hours after infection, mainly clustered for the reduction of cholesterol-rich metabolic proteins and the increase of modified proteins including carbohydrate and RNA shearsThen tested whether inhibiting splicing or glycozysolutions inhibited the replication of SARS-CoV-2, and found that the addition of splicing inhibitors pladienolide B (target-to-shear factor SF3B117) and 2-DG (an inhibitor of hisgykinase) could significantly prevent SARS-CoV-2 from replicating in the cellSARS-CoV-2 infection map reveals the cellular pathways necessary for replication
in order to identify other potential inhibitors for SARS-CoV-2 replication, the researchers detected a number of proteins similar to the change strains of viral proteins, mainly identified as the main metabolic pathway clusters of various nucleic acid metabolites pathwaysTherefore, the effect of nucleotide inhibitor ribavirin on REPLICATION of SARS-CoV-2 in cells was tested, and it was found that it inhibited SARS-CoV-2 replication at low micromole concentrations and clinically achievable concentrationsin addition to that, the researchers found that proteins associated with protein stability also showed a tendency to be highly similar to viral proteinsTherefore, the effect of protein steady-state disturbance on SARS-CoV-2 replication was tested using small molecular inhibitor NMS-873, and it was found that NMS-873 inhibited SARS-CoV-2 replication at low nanomole concentrations in a nutshell, the researchers revealed the cellular infection characteristics of SARS-CoV-2 and identified drugs that inhibit viral replication This result can guide understanding the molecular mechanisms of host cell regulation after SARS-CoV-2 infection, and also provide reference for the development of treatments for COVID-19 References: Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR.