The role of single-domain antibodies (or nanobodies) in SARS-CoV-2 neutralization

Abstract

The severe acute respiratory syndrome (SARS-CoV-2), a newly emerging of coronavirus, continues to infect humans in the absence of a viable treatment. Neutralizing antibodies that disrupt the interaction of RBD and ACE2 has been under the spotlight as a way of developing the COVID-19 treatment. Some animals, such as llamas, manufacture heavy-chain antibodies that have a single variable domain (VHH) instead of two variable domains (VH/VL) as opposed to typical antibodies. Nanobodies are antigen-specific, single-domain, changeable segments of camelid heavy chain-only antibodies that are recombinantly produced. These types of antibodies exhibit a wide range of strong physical and chemical properties, like high solubility, and stability. The VHH's high-affinity attachment to the receptor-binding domain (RBD) allowed the neutralization of SARS-CoV-2. To tackle COVID-19, some nanobodies are being developed against SARS-CoV-2, some of which have been recently included in clinical trials. Nanobody therapy may be useful in managing the COVID-19 pandemic as a potent and low-cost treatment. This paper describes the application of nanobodies as a new class of recombinant antibodies in COVID-19 treatment.

A Class of Shark‐Derived Single‐Domain Antibodies can Broadly Neutralize SARS‐Related Coronaviruses and the Structural Basis of Neutralization and Omicron Escape

“…A few camelid‐derived nanobodies against the RBD region of the SARS‐CoV‐2 Spike (S) protein have been reported recently. [ 24 , 25 , 26 , 27 ] We took a different approach by searching shark‐derived single domain antibodies, VNAR, which we termed it as vnarbodies to distinguish from camel‐derived nanobodies, for neutralizing SARS‐CoV‐2. Since shark blood and body fluids contain high concentration of urea (about 350 × 10 −3 m ), [ 28 ] shark‐derived vnarbodies may possess better physiochemical stability than human‐derived antibodies.…”

Monobodies with potent neutralizing activity against SARS-CoV-2 Delta and other variants of concern

“…Multimerization of the C4-AM2 or C6b monobodies could be a solution to improve IC 50 values, as dimerization and trimerization of a nanobody could improve the IC 50 values between 2 and 200 times against the SARS-CoV-2 wild type or pseudovirus ( Huo et al, 2020 ; Schoof et al, 2020 ; Xiang et al, 2020 ; Chen et al, 2021b ; Güttler et al, 2021 ; Koenig et al, 2021 ; Li et al, 2021 ; Xu et al, 2021 ; Zebardast et al, 2021 ). We know from previous research ( Kondo et al, 2020 ) that simple dimerization is insufficient to improve monobody activity.…”

“…Although numerous research studies and clinical tests prove that neutralizing antibodies effectively treat COVID-19 patients, the use of antibodies for common diseases’ treatment is challenging because it requires low-cost and large-scale antibody production ( Buyel et al, 2017 ; Corti et al, 2021 ). To solve this problem, single-domain antibodies ( Hamers-Casterman et al, 1993 ), also called nanobodies that bound to the RBD have been developed ( Esparza et al, 2020 ; Huo et al, 2020 ; Schoof et al, 2020 ; Xiang et al, 2020 ; Güttler et al, 2021 ; Koenig et al, 2021 ; Li et al, 2021 ; Sun et al, 2021 ; Xu et al, 2021 ; Ye et al, 2021 ; Zebardast et al, 2021 ; Chen et al, 2021b ). Nanobodies from a synthetic yeast library have shown moderate neutralizing activity in monomer form (a half-maximal inhibitory concentration; IC 50 = 6.3 nM) against the Wuhan SARS-CoV-2 pseudovirus and potent neutralizing activity in trimer form ( IC 50 = 120 pM) ( Schoof et al, 2020 ).…”

Nanobodies: from structure to applications in non-injectable and bispecific biotherapeutic development

“…Many excellent reviews provided excellent information and perspectives on the applications of nanobodies, including their applications in the study of the structures and functions of G protein-coupled receptors (GPCRs), 9 molecular imaging, 10 biosensing, 11 tumor diagnosis, 12 CAR-T therapy, 13 and the development of therapeutics against cancer and infectious diseases. 14,15 However, the structural basis of nanobodies for these applications has not been fully discussed. In addition, the applications of nanobodies in non-injectable and bispecific therapeutic developments were not covered in these early reviews.…”