CryoET analyzes the whole process of new coronavirus entering cells
- EPA Announces First-Ever Regulation for “Forever Chemicals” in Drinking Water
- Kochi University pioneers outpatient bladder cancer treatment using semiconductor lasers
- ASPEN 2024: Nutritional Therapy Strategies for Cancer and Critically Ill Patients
- Which lung cancer patients can benefit from neoadjuvant immunotherapy?
- Heme Iron Absorption: Why Meat Matters for Women’s Iron Needs
- “Miracle Weight-loss Drug” Semaglutide Is Not Always Effective
CryoET analyzes the whole process of new coronavirus entering cells
- Red Yeast Rice Scare Grips Japan: Over 114 Hospitalized and 5 Deaths
- Long COVID Brain Fog: Blood-Brain Barrier Damage and Persistent Inflammation
- FDA has mandated a top-level black box warning for all marketed CAR-T therapies
- Can people with high blood pressure eat peanuts?
- What is the difference between dopamine and dobutamine?
- How long can the patient live after heart stent surgery?
CryoET analyzes the whole process of new coronavirus entering cells.
Many studies have clarified the structure of the new coronavirus spike protein before and after fusion, but the specific process of the spike protein-mediated membrane fusion has not been studied in detail.
A new study , “Intermediates in SARS-CoV-2 spike-mediated cell entry,” published in Science Advances, provides refined structural biology information for understanding the intermediate states of spike protein fusions.
When SARS-CoV-2 infects cells, first S1 binds to the host cell membrane ACE2 and then undergoes secondary protease cleavage at S2′, and S2 undergoes a distinct structural transition from a prefusion conformation to a transiently extended intermediate inserted into the target host membrane.
The extended S2 intermediate is refolded through a “zipper” from the C-terminal heptapeptide repeat region (HRC/HR2) to the N-terminal heptapeptide repeat region (HRN/HR1), pulling the virus and host membranes together to initiate the activation of the viral cell membrane. Fusion and entry.
The final folded S2′ is a stable six-helix bundle, and the antiviral fusion inhibitory peptide can act on the HRC domain to interfere with the structural transition and inhibit fusion.
To capture the transient state of the structural transition, the researchers utilized a fusion inhibitory peptide [SARS HRC -PEG 4 ] 2 -chol .
The researchers used virus-like particles and targeted outer membrane vesicles to simulate the fusion of viruses and cells.
Under trypsin treatment, the two fused to produce fluorescence, which was blocked by the addition of peptide inhibitors.
This membrane fusion process is affected by temperature, and at 4°C the spike protein binds to the receptor without undergoing a conformational transition.
Using cryo-electron tomography, the researchers analyzed the conformation of the S2 extended intermediate and found that this region still retains considerable flexibility.
Fusion peptide inhibitors block viral entry mainly by locking S2 in a partially folded conformation.
Finally, based on the CryoET data, the researchers reconstructed the dynamic process of spike protein fusion.
First, the spike protein binds to the receptor, S2 activates elongation, S1 is released, and S2 refolds to form a partially folded intermediate state, and finally changes to post-membrane fusion.
Reference:
doi/10.1126/sciadv.abo3153
CryoET analyzes the whole process of new coronavirus entering cells
(source:internet, reference only)
Disclaimer of medicaltrend.org
Important Note: The information provided is for informational purposes only and should not be considered as medical advice.