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What Does The D614G Mutation Mean For COVID-19?

source:Qida organism  views:2175  time:2021-01-26

What Does The D614G Mutation Mean For COVID-19& Nbsp; SARS CoV-2 Changes Slowly In The Process Of Transmission. At The 614th Amino Acid Position Of Spike Protein, The Amino Acid Aspartic Acid (D, In Biochemical Abbreviation) Is Often Replaced By Glycine (G). Virologists Call It The D614G Mutation. Since The End Of February 2020, The Proportion Of The Mutant In The Detected Variation Has Become Higher And Higher, Making It The Most Common Identification Variation In Many Regions Of The World. This Attracted The Attention Of Researchers. Is D614G Mutation More Infectious/infectious Or More Lethal& Nbsp; Recently, A Research Article Entitled "Structure And Function Analysis Of D614G SARS-CoV-2 Spike Protein Variant" Was Published In The Magazine Cell. Scientists Studied D614G Mutation From Different Aspects Of Cell Biology And Structural Biology. We Will Take You Through Several Highlights Of This Article Below& Nbsp; According To The SARS CoV-2 Database Of GISAID As Of June 25, 2020, The Global Frequency Of S Protein D614G Variation Has Increased Steadily Over Time, And Currently There Are About 74% Of All Published Variations. (Figure 1)& Nbsp; Fig. 1 The Frequency Of D614G Mutation Of SARS CoV-2 S Protein Increased To Almost Constant During The Pandemic; In Order To Compare The Ability Of The Original S Protein D614 Or D614G Variant To Infect Virus Particles, They Constructed Pseudolentivirus. We Studied Several Different Cell Models, Including Calu-3 Human Lung Epithelial Cells, Caco-2 Human Colon Epithelial Cells, HEK293 Cells And SupT1 Cells (this Experimental Cell Can Be Provided By Shanghai Qida Biotechnology Co., Ltd.). It Can Be Seen From The Data That The Infectivity Of D614G Is 4 - 9 Times That Of D614& Nbsp;& Nbsp; Fig. 2 SARS CoV-2 D614G S Protein Enhances The Infectivity Of Pseudolentivirus In Cell Culture& Nbsp; In Order For SARS CoV-2 To Enter Human Cells, The Spike Protein On The Surface Of The Virus Must Bind To The Host Receptor Protein ACE2. Literature Of Cell Systems: Https://doi.org/10.1016/j.bbrc.2020.05.203  ; (Please Copy The Link To Read The Full Text) This Has Been Confirmed, And The Expression Change Of COVID-19 Receptor ACE2 In The Population At High Risk Of Cerebrovascular Disease And Ischemic Stroke "has Demonstrated The Research On Human Primary Brain Microvascular Endothelial Cells (ACBRI 376) Using Cell Systems. Although D614G Is Located Outside The Receptor Binding Domain, This Mutation May Change The Ace2 Binding Properties Through Allosteric Effects. It Can Be Seen From The Surface Plasmon Resonance (SPR) Results In Figure 3 That D614G Decreases The Affinity For ACE2 By Increasing The Dissociation Rate. These Data Indicate That The Increased Infectivity Of D614G Cannot Be Explained By The Stronger ACE2 Binding Strength& Nbsp;& Nbsp; The Combination Of SARS CoV-2 D614G S Protein Variant With ACE2 Is Weaker Than That Of The Original Protein. So Far, Most Therapeutic Antibodies Against COVID-19 Have Been Developed For The Receptor Binding Domain Of Spike Protein. Although This Structural Change Is Non Conservative, It Is Still A Question Whether It Will Affect The Effectiveness Of These Therapeutic Antibodies Currently Being Developed. They Did Some Research With Regenerative Antibodies., It Shows That D614G And The Original D614 Are Equally Sensitive To These Neutralizing Antibodies Targeting The Receptor Binding Region& Nbsp; Spike Protein Receptor Binding Domain Binds To ACE2 To Enter The Virus& Nbsp; In Order To Further Study Whether D614G Mutation Leads To Conformational Change, Scientists Conducted Low-temperature Electron Microscope Detection. They Found No Significant Change In S2 Subunit. However, D614G S1 Subunit Has Been Transferred, Resulting In Changes In The Conformation Of The Following Receptor Binding Domain (Fig. 6). We Can See That There Are 95% "up" Conformation In D614G, Which Greatly Increases The Chance Of Infection& Nbsp; Fig. 6 D614G Mutation Increased The Opening Of RBD 2 And RBD 3& Nbsp; At Present, Nearly 200 COVID-19 Vaccine Development Projects Are In Progress. In Evaluating The Effectiveness Of Vaccines, Scientists Usually Use Spike Proteins Or Receptor Binding Domains To Measure Antibody Titers. The 4x1 Step RT QPCR Probe Kit Recommended By HighQu Is Designed To Sensitively Detect Specific RNA, Including Viral RNA, In Diluted Large Volume Samples. They Combine A Powerful 4X QPCR Mixture (with Hot Start PCR Polymerase) And A 20 Fold Thermostable And Very Active Reverse Transcriptase And Advanced Ribonuclease Inhibitor (RT4 Mixture). This Formula Allows High Sample Input And Reliable Results Of One-step RT QPCR When Using Low Copy Number Samples Less Than 5 Copies Per Reaction. The 4x1 Step RT QPCR Probe Kit Ensures The Robust Performance Of Reverse Transcription And QPCR Reaction, Thus Realizing The Highest Sensitivity Of Viral RNA Detection Under The Conditions Of Fast QPCR Cycle. According To The Scheme Recommended By Charit é Berlin, Sars CoV-2 Virus Can Be Detected By The Performance Of The Kit With Appropriate Primers/probes. The PCR Water Provided In The Kit Ensures The Best Performance And Repeatability Of The Results. You Can Select Whether The Kit Has ROX, ROX L (low) And ROX H (high) Versions According To Your Instrument Requirements; Product Application: Detection Of Viral RNA In Diluted Low Copy Samples RT QPCR Analysis Of Sars CoV-2 Samples Based On Specific Probes: Including TaqMan ®、 Molecular Beacon, Scorpions ™& Nbsp; Quantitative Analysis Of Any RNA Template (mRNA, Total RNA, Viral RNA) And Low Copy Number Gene Of The Probe; Product Advantages: Powerful 4X QPCR Mixing Can Be Used For High Sample Size Up To 10 µ L Input For Each Reaction Detection< Five RNA Copies Successfully Detected Sars-CoV-2 Reverse Transcription And QPCR Can Be Used In The Same Test Tube To Achieve Ideal Multiple Reactions, Providing A Large Number Of Trial Kits, First Come, First Served 
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