Perspective on therapeutic and diagnostic potential of camel nanobodies for coronavirus disease-19 (COVID-19)

Abstract

In this paper, we focus on the camelid nanobodies as a revolutionary therapy that can guide efforts to discover new drugs for Coronavirus disease (COVID-19). The small size property makes nanobodies capable of penetrating efficiently into tissues and recognizing cryptic antigens. Strong antigen affinity and stability in the gastrointestinal tract allow them to be used via oral administration. In fact, the use of nanobodies as inhalant can be directly delivered to the target organ, conferring high pulmonary drug concentrations and low systemic drug concentrations and minimal systemic side effects. For that, nanobodies are referred as a class of next-generation antibodies. Nanobodies permit the construction of multivalent formats that may achieve ultra-high neutralization potency and then may prevent mutational escape and can neutralize a wide range of SARS-CoV-2 variants. Due to their distinctive characteristics, nanobodies can be of great use in the development of promising treatment or preventive strategies against SARS-CoV-2 infection. In this review, the state-of-the-art of camel nanobodies design strategies against the virus including SARS-CoV-2 are critically summarized. The application of general nanotechnology was also discussed to mitigate and control emerging SARS-CoV-2 infection.

Keywords: Antibodies engineering; Coronavirus disease (COVID-19); Heavy chain antibodies; Pandemic; Single-domain antibody.

Fig. 1

Schematic representation of the origin of COVID-19 cytokine storm. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters cells via binding to angiotensin-converting enzyme 2 receptor (ACE2). The rapid viral replication in the first infection stage leads to an inflammatory response and provokes an accumulation of large amounts of pro-inflammatory cytokines referred as cytokine storm ( adapted from de la Rica et al. 2020)

Fig. 2

Schematic diagram of camelid antibodies (a, b) and different Single-domain antibody fragment (VHH) constructions (c). a The common structure of conventional antibodies: The antigen-binding fragment (Fab) consisting of Variable Light (VL), Variable Heavy (VH), Constant Light (CL) and Constant Heavy 1 (CH1) domains. b The structure of homodimeric camelid antibody: The antigen-binding fragment lack the VL, CL and CH1 domains and named Single-domain antibody fragment (VHH). c Different VHH constructions (adapted from Smolarek et al. 2012)

Fig. 3

The potential mechanisms of SARS-CoV-2 neutralization by nanobodies. The major therapeutic goal is to develop inhibitory agents that disrupt the interaction between the receptor-binding domain of SARS-CoV-2 (green color) with its host cell receptor (angiotensin-converting enzyme 2: ACE2). Nanobodies bound directly to the receptor-binding domain (RBD) and competed with the ACE2 receptor from the surface of human cells (adapted from Esparza et al. 2020)