Shark vNAR antibodies inhibit SARS-CoV-2 variants in vitro

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Researchers in the UK and Austria have identified a novel class of antibodies that is highly effective at neutralizing the original strain of severe acute respiratory syndrome (SARS-CoV-2) and maintaining blocking activity against certain viral variants that have emerged.
The SARS-CoV-2 virus is the agent responsible for the ongoing coronavirus disease 19 (COVID-19) pandemic that has now claimed the lives of more than 3.76 million people.

The team identified ten single domain shark variable new antigen receptor (VNAR) antibody fragments that were highly effective at blocking the binding of the SARS-CoV-2 surface spike protein to its human host cell receptor angiotensin-converting enzyme 2 (ACE2).

The VNAR antibodies blocked the interaction between the receptor-binding domain (RBD) of the original Wuhan-Hu-1 spike protein and the ACE2 receptor. The antibodies also blocked this interaction when the spike proteins tested contained mutations found in the B.1.351 variant that emerged in South Africa and the P.1 variant that emerged in Brazil.

The team – from Ossianix Inc in Hertfordshire, Karl-Franzens-University in Graz and Medical University Graz – says that owing to their low complexity, small size, and formatting flexibility, single domain VNAR antibodies should be a useful adjunct to existing antibody approaches used in the treatment of COVID-19.

"VNAR antibodies directed against the SARS-CoV-2 spike protein expand the molecular toolbox of novel therapeutic approaches against COVID-19," writes Pawel Stocki and colleagues.

A pre-print version of the research paper is available on the bioRxiv* server, while the article undergoes peer review.

The progress so far in combatting COVID-19

The initial step of the SARS-CoV-2 infection process is mediated by the viral spike protein when its RBD attaches to the host cell receptor ACE2.

The extracellular domain of the spike comprises two subunits. The S1 subunit contains the RBD (S1-RBD), which makes direct contact with ACE2, while the S2 subunit drives host cell entry by enabling viral fusion to the cell membrane.

The S1-RBD is the primary target of neutralizing antibodies following SARS-CoV-2 infection. This domain, therefore quickly became the main focus of efforts to develop…
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