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The evolution of coronaviruses, such as SARS-CoV-2, has made broad-spectrum coronavirus prevention or treatment strategies highly sought after
.
This article reports a monoclonal antibody 3E8 against human angiotensin-converting enzyme 2 (ACE2), which can block SARS-CoV-2, SARS-CoV-2 variants, SARS-CoV-NL63 and other coronaviruses The S1 subunit and pseudotyped virus structure have no obvious effect on the physiological activity of ACE2, nor will it cause serious toxicity to ACE2 "knock-in" mice
In the past 20 years, the coronavirus has caused three major infectious disease outbreaks in humans, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and coronavirus disease 2019 (COVID-19)
.
One of the challenges in controlling coronaviruses is that they continue to evolve, albeit slower than HIV and influenza
The key to developing broad-spectrum coronavirus therapies is to identify broad-spectrum antiviral targets
.
Although RNA polymerase is a broad anti-RNA virus target, its specificity and effectiveness are low
The infection of SARS-CoV-2 is triggered by the binding of its envelope stimulating glycoprotein (S protein) to angiotensin-converting enzyme 2 (ACE2) molecules expressed by host cells
.
The S protein is composed of two subunits: (1) the N-terminal S1 subunit (also known as the S1 protein), which contains the receptor binding domain (RBD) responsible for ACE2 binding; (2) the C-terminal S2 subunit, which is responsible for membrane fusion
Frozen EM structure of 3E8/ACE2-B0AT1 complex and "alanine walking" study to solve the key interaction between 3E8 and ACE2
Image source: https://doi.
org/10.
1038/s41392-021-00740-y
ACE2 is a type I transmembrane glycoprotein, which plays an important role in maintaining blood pressure homeostasis in the renin-angiotensin system
.
It is the shared receptor of multiple coronaviruses, such as SARS-CoV-2, SARS-CoV, HCoV-NL63, 17, 26, 27 bat coronavirus RaTG13, 28 pangolin coronavirus GX/ P2V/2017 and GD/1/ 2019
To test this hypothesis, the authors generated a monoclonal antibody, 3E8, to target the RBD binding site on ACE2
.
The therapeutic potential and safety of 3E8 were studied, and the key binding sites of 3E8 on the human ACE2 molecule were revealed through cryo-EM and mutation studies
Note: The original text has been deleted
references
Yuning Chen et al.
