Friday, July 1, 2022
No Result
View All Result
Medical Finance
  • Home
  • News
  • Interviews
  • Mediknowledge
  • Insights From Industry
  • Thought Leaders
  • Coronavirus
  • Whitepapers
  • Home
  • News
  • Interviews
  • Mediknowledge
  • Insights From Industry
  • Thought Leaders
  • Coronavirus
  • Whitepapers
No Result
View All Result
Medical Finance
No Result
View All Result
Home Coronavirus

Ultralong bovine antibody targets cryptic and conserved epitope on SARS-CoV and SARS-CoV-2

by Medical Finance
in Coronavirus
Study: An Ultralong Bovine CDRH3 that Targets a Conserved, Cryptic Epitope on SARS-CoV and SARS-CoV-2. Image Credit: PHOTOCREO Michal Bednarek/Shutterstock
9
SHARES
99
VIEWS
Share on FacebookShare on Twitter

In a recent article posted to the bioRxiv* preprint server, researchers identified an ultralong bovine antibody that neutralizes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severe acute respiratory syndrome coronavirus (SARS-CoV).

Study: An Ultralong Bovine CDRH3 that Targets a Conserved, Cryptic Epitope on SARS-CoV and SARS-CoV-2. Image Credit: PHOTOCREO Michal Bednarek/Shutterstock
Study: An Ultralong Bovine CDRH3 that Targets a Conserved, Cryptic Epitope on SARS-CoV and SARS-CoV-2. Image Credit: PHOTOCREO Michal Bednarek/Shutterstock

Background

The coronavirus disease 2019 (COVID-19) pandemic has brought to light the enormous threat that zoonotic and highly transmissible pathogens pose to the global populations, specifically when prior immunity is limited.

Although COVID-19 vaccinations have shown to be quite effective in decreasing SARS-CoV-2 transmission and averting severe illness, this might not be the case for all pathogens. Furthermore, not everyone develops sufficient immunity following SARS-CoV-2 vaccinations, necessitating the development of additional therapies that can be implemented quickly in the event of a new pathogen.

Broadly neutralizing antibodies target conserved epitopes and have a lot of potential as antibody-based treatments, especially given the continuous evolution of SARS-COV-2 antigens. Some bovine antibodies are highly proficient at binding conserved, glycosylated epitopes because of their ultralong complementarity determining region heavy chain 3 (CDRH3). Moreover, the longest known CDRH3 domains are possessed by bovine ultralong antibodies.

About the study

In the present study, the scientists isolated ultralong bovine H-chains with neutralizing capacity against SARS-CoV-2 and similar CoVs. Based on prior reports that the ultralong bovine H-chains couple with a comparatively invariable Vλ light chain, the team built a single-chain variable fragment (scFv) framework to which ultralong H-chain-only libraries could be cloned and produced. 

The researchers employed polyhistidine-tagged (His-tagged) SARS-CoV-2 spike (S) glycoprotein and mammalian cell surface display to isolate an ultralong scFv from a SARS-CoV-2-naïve H-chain library that engages with the receptor-binding domains (RBDs) of SARS-CoV and all the existing SARS-CoV-2 variants. Further, human embryonic kidney 293T (HEK293T) cells were used for mammalian cell culture. The researchers utilized site-directed mutagenesis and differential hydrogen-deuterium exchange mass spectrometry (HDX-MS) to determine the mechanism of neutralization of lentiviruses pseudotyped with SARS-CoV-2 S and SARS-CoV S protein by the identified bovine paratope. 

Findings and discussions

The study results demonstrated the discovery of a bovine extensively reactive CDRH3, named B9-scFv, from a library of <1 x 104 SARS-CoV-2-naïve H-chain sequences. The isolated ultralong B9-scFv interacted with RBDs of SARS-CoV and all prevailing SARS-CoV-2 variants. Additionally, the ultralong CDRH3 bound to SARS-CoV RBD approximately 50-times more strongly than SARS-CoV-2.

The bovine antibody-targeted epitope was found in a cryptic cleft on the inner region of the SARS-CoV and SARS-CoV-2 RBD, which was only accessible transiently due to inter-domain motions. This epitope was only discovered once previously as the target for two different pan-sarbecovirus antibodies (7D6 and 6D6) when several repeated vaccinations were necessary.

In addition, five vaccinations of mice with either a combination of SARS-CoV and SARS-CoV-2 S protein and the Middle East Respiratory Syndrome CoV (MERS-CoV) RBD protein or SARS-CoV-2 S-2 subunit protein (S-2P) were required for the isolation of the 7D6 and 6D6 antibodies. On the contrary, from a limited library of bovine CDRH3s, B9-scFv was isolated in the present study. Furthermore, the 7D6 and 6D6 antibodies demonstrated destabilization of the perfusion S complex.

B9-scFv did not demonstrate competition with SARS-CoV pseudotyped lentiviruses for angiotensin-converting enzyme 2 (ACE2) interaction. Yet, B9-scFv neutralized SARS-CoV pseudotyped viruses with a half-maximal inhibitory concentration (IC50) of 468 nM, most likely by disrupting the stability of the prefusion complex via a crucial glycan contact interference. Mutagenesis and HDX data depicted numerous critical contacts which were shared between the epitope of B9-scFv and 7D6 and 6D6 antibodies, including 457-467 residues on the β7-β8 loop of the RBD.

B9-scFv demonstrated a truncated descending and ascending β-stranded stalk, with few residues at the 101RD102 variable diversity (VD) junction and no alternate tyrosine motif at the 3’ terminus of D8-2. These characteristics would most likely affect the stalk’s angle, length, and flexibility and the manner in which the disulfide-bonded loops of the B9 knob domain interact with the CoVs RBD proteins.

Conclusions

The study findings demonstrated the identification of a bovine ultralong CDRH3, named B9-scFc, that neutralized viruses pseudotyped with SARS-CoV and all current SARS-CoV-2 variants’ S protein but not via competing with viral RBD for ACE2 receptor binding.

The researchers found that the presently discovered ultralong CDRH3 neutralized the SARS-CoV S protein via the identification of a conserved, seldom seen, and cryptic epitope that overlaps the target of 7D6 and 6D6 pan-sarbecovirus antibodies. The B9-scFc-targeted epitope in SARS-CoV-2 and SARS-CoV was glycan-shielded and only became temporarily accessible through inter-domain movements.

Overall, the present investigation identified the first bovine anti-sarbecovirus paratope and illustrated the potential of the bovine system for rapidly discovering widely reactive new ultralong CDRH3s targeting conserved vulnerable sites on emerging viral pathogens and their variants.

*Important notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Total
0
Shares
Share 0
Tweet 0
Pin it 0
Share 0
Medical Finance

Medical Finance

Related Posts

Study: Tuftsin: a natural molecule against SARS-CoV-2 infection. ​​​​​​​Image Credit: NIAID

The tetrapeptide tuftsin effectively impairs the binding of SARS-CoV-2 S1 to ACE2

by Medical Finance
June 30, 2022
0

Several prophylactic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are being used across the globe to control the spread...

Combing Raman spectroscopy and chemometrics for estimating post-mortem interval in human remains

Messenger RNA can be used at low doses to regenerate bone without side effects

by Medical Finance
June 30, 2022
0

Although fractures normally heal, bone will not regenerate under several circumstances. When bone does not regenerate, major clinical problems could...

Study: Co-infection with SARS-COV-2 Omicron and Delta Variants Revealed by Genomic Surveillance. Image Credit: G.Tbov/Shutterstock

First cases of co-infection with Delta and Omicron identified during local co-circulation of both SARS-CoV-2 lineages

by Medical Finance
June 30, 2022
0

In a recent study posted to the medRxiv* preprint server, researchers revealed the co-infection of the severe acute respiratory syndrome...

Study: Trends in non-COVID-19 hospitalizations prior to and during the COVID-19 pandemic period, United States, 2017 – 2021. Image Credit: Gorodenkoff/Shutterstock

Exploring changes in non-COVID-19 hospitalization rates before and during COVID-19

by Medical Finance
June 30, 2022
0

In a recent study posted to the medRxiv* preprint server, researchers assessed the trends in non-coronavirus disease 2019 (COVID-19) hospitalizations...

Study: Increased Potency and Breadth of SARS-CoV-2 Neutralizing Antibodies After a Third mRNA Vaccine Dose. Image Credit: Kateryna Kon/Shutterstock

Memory B cell repertoire in a longitudinal cohort of individuals receiving 3 COVID-19 mRNA vaccine doses

by Medical Finance
June 30, 2022
0

In a recent study posted to the bioRxiv* preprint server, a team of researchers examined the memory B cell repertoire...

Study: P681 mutations within the polybasic motif of spike dictate fusogenicity and syncytia formation of SARS CoV-2 variants. Image Credit: Lightspring/Shutterstock

P681 mutations in SARS-CoV-2 spike protein determine fusogenicity

by Medical Finance
June 30, 2022
0

In a recent study posted to the bioRxiv* preprint server, researchers evaluated the importance of the P681 residue within the...

Next Post
Study: Limitations of molecular and antigen test performance for SARS-CoV-2 in symptomatic and asymptomatic COVID-19 contacts. Image Credit: anyaivanova/Shutterstock

Comparison of SARS-CoV-2 test performance by sample type and modality in close contacts of SARS-CoV-2 cases

Study: Mutations of Omicron variant at the interface of the receptor domain motif and human angiotensin-converting enzyme-2. Image Credit: Lightspring/Shutterstock

The effect of Omicron mutations at the fundamental atomic scale level

0 0 votes
Article Rating
Subscribe
Login
Notify of
guest
guest
0 Comments
Inline Feedbacks
View all comments

Support

  • Contact
  • Disclaimer
  • Home
  • Privacy Policy
  • Terms And Conditions

Categories

  • Coronavirus
  • Insights From Industry
  • Interviews
  • Mediknowledge
  • News
  • Thought Leaders
  • Whitepapers

More News

  • Anatomy of Human Heart. Liya Graphics 5ac9d64765b747899bc4a9ef77468432 620x480
    Gene replacement therapy could help mend a broken heart, study suggests
  • Abstract medicine background Hilch 1000 f0a8c263e6e04ed18dfcc5ef27c17907 620x480
    New CDC analyses shine light on mental health of U.S. high school students during the pandemic
  • Home
  • Privacy Policy
  • Contact
  • Disclaimer
  • Terms And Conditions

© 2022 Medical Finance - Latest Financial and Business News

No Result
View All Result
  • Interviews
  • Mediknowledge
  • News
  • Insights From Industry
  • Coronavirus
  • Thought Leaders
  • Whitepapers
wpDiscuz
0
0
Would love your thoughts, please comment.x
()
x
| Reply