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

 Researchers based in Belgium have developed a replacement antibody drug that's highly successful at neutralizing coronavirus disease 2019 (COVID-19) in Syrian hamsters. The new biologic was administered to the rodents and was found to be equally successful at neutralizing the first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain, and also the new mutant variants, like the South African and UK strains.


A pre-print version of the research paper is out there to read fully on the bioRxiv* server.

Antibody immunity

Vaccines represent potent tools for combatting diseases, however, they're limited in some regards. Immunity could also be short-lived or less effective in adulthood groups. Limited vaccine availability in many countries, vaccine hesitancy, are other factors of which the impact is currently uncertain.

Passive antibody immunotherapy provides an alternate. Antibodies have long half-lives, are easily and quickly replicable, and, specifically, are capable of being broadly neutralizing. Antibodies with this ability are often more successful within a system as they will be effective against multiple mutant variants of an epidemic, instead of having limited efficacy to at least one strain.

Nico Callewaert, Xavier Saelens, and colleagues have developed a replacement heavy chain-only antibody, named XVR011, that's equally potent against multiple SARS-CoV-2 variants. Not only that, but it's highly stable, and has “excellent manufacturability.”

Previously, researchers had been ready to replicate a prototype antibody, VHH72, that was effective in protecting mice from SARS-CoV-2 infection. during this study, they were ready to modify and increase the efficacy of the antibody using computer models. These antibodies were then tested on Syrian hamsters and successfully reduced remnant viral RNA within the lung cavity of the animals.

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The team then went on to optimize the antibody molecules, and further tested these antibodies against more virulent strains of the virus in hamsters. This new protein was dubbed XVR011 and was found to be equally potent against the united kingdom and South Africa variants of the virus (B.1.1.7. and B.1.351, respectively). XVR011 is additionally not reactive with other human proteins and is restricted to viral RNA, supporting the potential use of it for medicinal purposes.

Enhanced affinity and neutralizing activity of computationally predicted VHH72 variant. Left: Composite overlay showing the locations of VHH72 (grey cartoon with the transparent surface, center-left) and ACE-2 (orange cartoon, top) versus SARS-CoV-2 RBD (cyan cartoon, center). Tyr369 of SARS-CoV-2 RBD is indicated and shown as purple sticks. The protein-proximal monosaccharides of the ACE-2 N322 N-glycan (clashing with VHH72) are shown as orange sticks; the RBD N343 N-glycan’s protein-proximal monosaccharides are shown as cyan sticks. The emerging RBD variants at residues K417(->N), N439(->K), L452(->R), S477(->N), E484(->K) and N501(->Y) are indicated and shown as yellow sticks. Right: Comparison of VHH72 (rainbow cartoon) in complex with SARS-CoV-1 RBD (cyan cartoon, PDB-entry 6WAQ chains C and D) with a homology model of VHH72 sure to SARS-CoV-2 RBD (cyan cartoon, the model obtained from the I-TASER server), zoomed-in to the zone near VHH72's S56. VHH72 residues S52, W52a, S53, S56, and V100, SARS-CoV-1 RBD residues Y352, Y356 (purple), N357, S358, T359 and A371, and SARS-CoV-2 RBD residues Y365, Y369 (purple), N370, S371, A372, and P384 are shown as sticks. Figures generated with Pymol (The PyMOL Molecular Graphics System, Open Source Version 2.3. Schrödinger, LLC). RBD Tyr369 assumes a differential preferential conformation between SARS-CoV-1 and SARS-CoV-2, imposed by the P384 in SARS-CoV-2. Accommodating this alteration was the main target of our structure-guided affinity maturation campaign of VHH72.

“Happy to report on our work… developing a really potent, cross-clade binding, VoC-resistant VHH-Fc antibody drug” tweeted Nico Callewaert. Callewaert is one of the paper's lead authors and a professor at the University of Gent, Belgium.

Such enhanced antibodies could also be utilized for longer-term immunity against potential new SARS-CoV-2 variants within the future and will become crucial in protecting populations until they're ready to receive a vaccination. Additionally, as this antibody appears to figure across multiple variants of SARS-CoV-2, it might be instrumental in slowing the spread of mutant strains which can have previously escaped immunization from current vaccines.

*Important Notice

bioRxiv publishes preliminary scientific reports that aren't peer-reviewed and, therefore, shouldn't be considered conclusive, guide clinical practice/health-related behavior, or treated as established information.

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