Nanobody works against all variants of SARS-CoV-2 stress in an animal model

Belgian-based researchers have developed a new antibody drug that is highly successful in neutralizing coronavirus infection 2019 (COVID-19) in Syrian hamsters. The rodents were given the new biologist and found to be just as successful in neutralizing the old respiratory coronavirus 2 (SARS-CoV-2) syndrome, as well as the new mutant variants, such as strains. South Africa and the UK.

A pre-printed version of the full research paper can be found on the bioRxiv* server.

Antibody immunity

Vaccines represent strong tools for combating disease, however, they are limited in some ways. Immunity can be short-lived or less effective in older age groups. Availability of vaccines in many countries, vaccine laziness, are other reasons for which the effect is currently uncertain.

Passive antibody immunotherapy offers an alternative. Antibodies have a long half-life, are easily reproducible, and in particular, they are generally able to neutralize. Antibodies with this ability can be more successful within the immune system because they can be effective against several mutant mutations of a virus, rather than being effective to a single strain.

Nico Callewaert, Xavier Saelens and colleagues have developed a new heavy-chain antibody-only, called XVR011, which is equally potent against several SARS-CoV-2 modifications. Not only that, but it is very durable, and has “excellent manufacturing capacity.”

Previously, researchers had been able to reproduce a prototype antibody, VHH72, which was effective in protecting mice from SARS-CoV-2 infection. In this study, they were able to modify and increase the efficacy of the antibody using computer models. These antibodies were then tested on Syrian hamsters and reduced viral RNA remaining in the lung caverns of the animals.

The team then proceeded to maximize the antibody molecules, and further tested these antibodies against more active strains of the virus in hamsters. This new protein has been dubbed XVR011, and has been found to be equally potent against mutation of the virus in the UK and South Africa (B.1.1.7. And B.1.351, respectively). XVR011 is also not reactive with other human proteins, and is specific to viral RNA, supporting potential use for pharmacological purposes.

Improved correlation and neutral activity of computer-predicted variant of VHH72.  Left: Multiple reversal showing locations of VHH72 (gray cartoon with visible surface, center-left) and ACE-2 (orange cartoon, top) versus SARS-CoV-2 RBD (cyan cartoon, center).  Tyr369 of SARS-CoV-2 RBD is identified and shown as purple mats.  The protein-proximal monosaccharides of the ACE-2 N322 N-glycan (anti-VHH72) are shown as orange mats;  RBD N343 N-glycan protein-proximal monosaccharides are shown as cyan mats.  The emerging RBD variables are at residues K417 (- /> N), N439 (-> K), L452 (-> R), S477 (-> N), E484 (-> K) and N501 (-> Y) marked and shown as yellow matches.  Right: Comparison of VHH72 (rainbow cartoon) in complex with SARS-CoV-1 RBD (cyan cartoon, pdb-entry chains 6WAQ C and D) with homology model of VHH72 linked to SARS-CoV-2 RBD (cyan cartoon , a model obtained from the I-TASSER server), extended into the zone near VHH72″ height”368″ src =”https://d2jx2rerrg6sh3.cloudfront.net/image-handler/picture/2021/3/seure.jpg” srcset =”https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210311124406/ri/1137/picture/2021/3/seure.jpg 1137w, https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210311124406 /ri/1050/picture/2021/3/seure.jpg 1050w, https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210311124406/ri/850/picture/2021/3/seure.jpg 850w, https : //d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210311124406/ri/650/picture/2021/3/seure.jpg 650w, https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20210311124406/ ri / 450 / image / 2021/3 / seure.jpg 450w” meudan =”(min-width: 1200px) 673px, (min-width: 1090px) 667px, (min-width: 992px) calc (66.6vw – 60px), (min-width: 480px) calc (100vw – 40px), calc (100vw – 30px)” title”Improved correlation and neutral activity of computer-predicted variant of VHH72.  Left: Multiple reversal showing locations of VHH72 (gray cartoon with visible surface, center-left) and ACE-2 (orange cartoon, top) versus SARS-CoV-2 RBD (cyan cartoon, center).  Tyr369 of SARS-CoV-2 RBD is identified and shown as purple mats.  The protein-proximal monosaccharides of the ACE-2 N322 N-glycan (anti-VHH72) are shown as orange mats;  RBD N343 N-glycan protein-proximal monosaccharides are shown as cyan mats.  The emerging RBD variables are at residues K417 (-> N), N439 (-> K), L452 (-> R), S477 (-> N), E484 (-> K) and N501 ( -> Y) marked and shown as yellow matches.  Right: Comparison of VHH72 (rainbow cartoon) in complex with SARS-CoV-1 RBD (cyan cartoon, pdb-entry chains 6WAQ C and D) with homology model of VHH72 linked to SARS-CoV-2 RBD (cyan cartoon , a model obtained from the I-TASSER server), extended into the zone near VHH72″ width =”1137″/></p>
<p><span style=Improved correlation and neutral activity of computer-predicted variant of VHH72. Left: Multiple reversal showing locations of VHH72 (gray cartoon with visible surface, center-left) and ACE-2 (orange cartoon, top) versus SARS-CoV-2 RBD (cyan cartoon, center). Tyr369 of SARS-CoV-2 RBD is identified and shown as purple mats. The protein-proximal monosaccharides of the ACE-2 N322 N-glycan (anti-VHH72) are shown as orange mats; RBD N343 N-glycan protein-proximal monosaccharides are shown as cyan mats. The emerging RBD variables are at residues K417 (-> N), N439 (-> K), L452 (-> R), S477 (-> N), E484 (-> K) and N501 ( -> Y) marked and shown as yellow matches. Right: Comparison of VHH72 (rainbow cartoon) in complex with SARS-CoV-1 RBD (cyan cartoon, pdb-entry chains 6WAQ C and D) with homology model of VHH72 linked to SARS-CoV-2 RBD (cyan cartoon , a model obtained from the I-TASSER server), brought into the zone near VHH72’s S56. Residual VHH72 S52, W52a, S53, S56 and V100, RBD residue SARS-CoV-1 Y352, Y356 (purple), N357, S358, T359 and A371, and RBD residue SARS-CoV-2 Y365, Y369 (purple), N370 , S371, A372 and P384 shown as matches. Figures generated by Pymol (PyMOL Molecular Graphics System, Open Source Version 2.3. Schrödinger, LLC). RBD Tyr369 assumes a different favorable compatibility between SARS-CoV-1 and SARS-CoV-2, placed the P384 in SARS-CoV-2. Adopting this change was the focus of our structural relationship maturation campaign of VHH72.

“We are pleased to report on our work… developing a strong, cross-linked, VHH-Fc antibody drug that counteracts VoC” tweets Nico Callewaert. Callewaert is one of the leading authors of the paper and a professor at the University of Ghent, Belgium.

Such enhanced antibodies can be used for long-term immunity against new SARS-CoV-2 mutations in the future and may be crucial in protecting populations in order to obtain vaccines. Furthermore, since this antibody appears to work over several mutations of SARS-CoV-2, it may be instrumental in slowing the release of mutant sequences that may have been vaccinated from the standard vaccines.

* Important message

bioRxiv publish preliminary scientific reports that are not peer-reviewed and, therefore, should not be seen as final, guiding health-related clinical practice / behavior, or be treated as information established.

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