Abstract
Nanobodies are 130 amino acid single-domain antibodies (VHH) derived from the unique heavy-chain-only subclass of Camelid immunogloblins. Their small molecular size, facile expression, high affinity and stability have combined to make them unique targeting reagents with numerous applications in the biomedical sciences. The first nanobody agent has now entered the clinic as a treatment against a blood disorder. The spread of the SARS-CoV-2 virus has seen the global scientific endeavour work to accelerate the development of technologies to try to defeat a pandemic that has now killed over four million people. In a remarkably short period of time, multiple studies have reported nanobodies directed against the viral Spike protein. Several agents have been tested in culture and demonstrate potent neutralisation of the virus or pseudovirus. A few agents have completed animal trials with very encouraging results showing their potential for treating infection. Here, we discuss the structural features that guide the nanobody recognition of the receptor binding domain of the Spike protein of SARS-CoV-2.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the seventh coronavirus that has infected humans [1] and, like SARS-CoV and MERS-CoV, infection can result in severe diseases [1]
VH H72 binds to the RBD molecule in a manner which competes with angiotensin-converting enzyme 2 (ACE2) binding due to steric clashes (Figure 2a)
Antibodies that cross-react with SARS-CoV-1 and potentially other closely related bat beta-coronaviruses come from Classes 3 and 4, reflecting the higher sequence conservation in the region of the RBD recognised by these antibodies
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the seventh coronavirus that has infected humans [1] and, like SARS-CoV and MERS-CoV, infection can result in severe diseases [1]. Several therapies based on human monoclonal antibodies have been approved for use; a recent overview of progress in this field has been published [7]. These molecules work by binding to the Spike protein of the virus and preventing it from engaging with the angiotensin-converting enzyme 2 (ACE2). Human antibodies are comprised of two protein chains, the heavy and the light chain (Figure 1a). Studies have already shown that highly potent anti-COVID-19 nanobodies can be administered by injection and by inhalation with potent therapeutic effect. (b) Camelid antibodies only have a heavy chain; the CDRs (yellow tips) are located within one domain (red).
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