-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
-
Cosmetic Ingredient
- Water Treatment Chemical
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
"Host range and structural analysis of bat-origin RshSTT182/200 coronavirus binding to human ACE2 and its animal orthologs", the study The structure of the RshSTT182/200 receptor-binding domain (RBD) and human angiotensin-converting enzyme 2 (hACE2) complexes was determined, and key residues
affecting receptor binding were identified.
The study combined RshSTT182/200 RBD with ACE2 orthologs from 39 animals, including 18 species of bats, and has assessed its host range
.
RshSTT182/200 RBD broadly identified 21 of the 39 ACE2 orthogenes, although its binding affinity with the orthocompounds was weaker than that of SARS-CoV-2 RBD
.
In addition, the RshSTT182 pseudovirus can enter cells
using the ACE2 receptors of humans, foxes, and nasal frogs.
The researchers also found that SARS-CoV-2 induced cross-neutralizing antibodies
against the RshSTT182 pseudovirus.
Taken together, these findings suggest that RshSTT182/200 may infect susceptible animals, but further evolution is needed to acquire a capacity for interspecific transmission as strong as SARS-CoV-2
.
Seven coronaviruses have been reported to infect humans, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), human coronavirus NL63 (HCoV-NL63), human coronavirus OC43 (HCoV-OC43), human coronavirus 229E ( HCoV-229E), human coronavirus HKU1 (HCoV-HKU1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
In the last 20 years, three public health emergencies have been caused by coronaviruses: the SARS-CoV pandemic (2002), the MERS-CoV pandemic (2012), and the SARS-CoV-2 pandemic (2019).
For many viral infectious diseases, the discovery of viruses often lags by decades or more
.
For example, HCoV-HKU1 was first detected
in 2004 in a patient with pneumonia in Hong Kong, China.
However, a frozen nasopharyngeal swab sample from a Brazilian child in 1995 tested positive for HCoV-HKU1, indicating that HCoV-HKU1 had been circulating in the population for a long time
.
MERS-CoV was first detected in Saudi Arabia in 2012, while 81% of dromedary serum samples collected in Egypt in 1997 and in Sudan and Somalia in 1983-1984 were positive
for MERS-CoV neutralizing antibodies.
Therefore, assessing potential interspecific transmission of the virus is an effective way
to raise infectious disease alert as early as possible.
Bats are thought to host
HCoV-NL63, HCoV-229E, SARS-CoV, and MERS-CoV.
At the beginning of the SARS-CoV-2 pandemic, several SARS-CoV-2-related coronaviruses
were detected in bats.
The overall genome of bat-derived coronavirus RaTG13 is 96.
2%
identical to the nucleic acid sequence of SARS-CoV-2.
Another coronavirus derived from bats, RmYN02, contains a 3-amino acid residue (PAA) insertion site at the S1/S2 cleavage site of its spike protein, which is similar to SARS-CoV-2, while this has not been observed in other SARS-CoV-2-related coronaviruses
.
The furin protease cleavage site (FCS) plays a key role in SARS-CoV-2 infection, and the absence of this site reduces viral entry efficiency
.
Recently, several bat-source CoVs, BANAL-52, BANAL-103 and BANAL-236
, have been identified in bat bodies in northern Laos.
The receptor-binding domains (RBDs) of the spike proteins of BANAL-52, BANAL-103, and BANAL-236 are 95% identical to those of SARS-CoV-2 and exhibit similar binding affinities to SARS-CoV-2 RBD and hACE2, suggesting that these viruses may infect humans
。 RshSTT182 and RshSTT200 are the first SARS-CoV-2-associated coronaviruses detected in Southeast Asia (Cambodia) with a genome-wide homology of 92.
6%
with SARS-CoV-2.
RshSTT182 and RshSTT200 RBD have the same amino acid sequence and have 84.
3% homology with SARS-CoV-2 RBD
.
Interspecific receptor recognition by SARS-CoV, SARS-CoV-2, RaTG13, GX/P2V/2017, and GD/1/2019 has been
evaluated.
All of these coronaviruses widely identify different ACE2 congeners, suggesting that they may be circulating
between different animals.
In addition, several cases
of natural infection with SARS-CoV-2 have been reported.
Cats, dogs, lions and tigers in zoos, as well as mink, ferrets, snow leopards, cougars and gorillas in nature, have been found to have contracted SARS-CoV-2
through exposure to people with COVID-19.
In addition, the SARS-CoV-2 strain associated with mink has spread back to humans and caused further community transmission
.
The overall structure of RshSTT182/200 RBD binding to hACE2 (Figure from EMBO Journal) It is worth noting that SARS-CoV-2 variants were detected in infected mink, suggesting that interspecific transmission may produce new variants
.
RshSTT182/200 RBD is highly conserved with SARS-CoV-2 RBD and may also have a wide host range
.
Host cell receptor binding is a prerequisite for
viral infection.
Therefore, describing the interaction between RBD of CoV and ACE2 orthologs from a wide range of species is an effective method
to screen potential hosts.
Receptor binding is the first step
in coronavirus infection.
A range of protein and carbohydrate receptors/cofactors have been identified
.
ACE2 is the main receptor for SARS-CoV, SARS-CoV-2 and its related coV, such as RaTG13, GX/P2V/2017, GD/1/2019
.
The structure of SARS-CoV-2 RBD complexes with ACE2s complexes in humans, cats, bats, dogs, martens and pangolins has been determined
.
In addition, the structure of hACE2 binding to RaTG13, GX/P2V/2017 and GD/1/2019 RBDs has been studied
.
GX/P2V/2017 RBD and GD/1/2019 RBD utilize similar binding mechanisms to SARS-CoV-2 and show similar binding affinity
to hACE2 with SARS-CoV-2 RBD.
Similar to other CoVs associated with SARS-CoV-2, RshSTT182/200 also uses ACE2 as its receptor.
However, the molecular details of RshSTT182/200 RBD binding to ACE2 are unknown
.
In this study, the researchers found that RshSTT182/200 RBD has a much lower binding affinity for hACE2 than SARS-CoV-2 RBD
.
They determined the structure of the RshSTT182/200 RBD with hACE2 complexes and identified key residues
.
As a kind of batThe receptor binding spectrum of the source coronavirus, RshSTT182/200, in 18 species of bats is narrower
than that of SARS-CoV-2.
In addition, the study evaluated the receptor binding profile
of RshSTT182/200 RBD with 21 animal ACE2 homologous sequences, including hACE2.
RshSTT182/200 RBD extensively identified 16 of the 21 ACE2 orthogenites with significantly lower binding affinity than SARS-CoV-2
.
ACE2 receptors in humans, foxes, and R.
affinis support VSV-based RshSTT182 pseudoviral transduction, but hACE2-mediated entry is less efficient
.
In addition, serum of SARS-CoV-2 convalescent patients or vaccinated patients can cross-neutralize VSV-based RshSTT182 pseudovirus, and SARS-CoV-2 monoclonal antibodies S309, BD-368-2, and BD-604 can cross-identify RshSTT182/200 RBD
.
These results suggest that surveillance of RshSTT182/200 and its associated coronaviruses carried by potential animal reservoirs should be intensified to prevent potential pandemics
.
Paper information: https://doi.
org/10.
15252/embj.
2022111737 Source: iNature
。 The content of the article is only for academic sharing, the copyright belongs to the original author and the platform, if there is infringement, please contact us to delete, thank you
👇 Click to get more academic information 👇
Click on to see your best look
