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 . 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.

Emerging SARS-CoV-2 variants of concern and potential intervention approaches

“…In order to avoid antibody escape, strategies to combine different neutralizing antibody cocktail have been suggested as a therapeutic approach against the emerging variants [76]. Other treatments such as anti-RBD nanobodies isolated from llamas were shown to neutralize RBD variants suggesting they might be a promising tool against new SARS-CoV-2 VOCs as well [77,78].…”

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

“…Nanobodies offer novel tools to modulate inflammatory responses in COVID-19 patients [ 81 ]. By targeting chemokines and cytokines, they can be adjusted to control inflammation responses, which contributes to COVID-19 patients' recovery [ 16 ]. For example, the isolation of anti-CXCL10 polyclonal HcAbs has been conducted to create specific Nbs, which can selectively target CXCL10 for in vivo therapies [ 82 ].…”

“…APCs contain high levels of MHC-II products, integrins (CD11b), and scavenger receptors (CD36). VHHs targeting these molecules improved immune responses in dendritic cells (DCs), induced humoral immunity, and detected inflammation in order to cure or prevent SARS-CoV-2 infection [ 16 , 84 ].…”

“…The interaction of the RBD of the viral spike with the cellular receptor, known as angiotensin-converting enzyme 2 (ACE2), is required for SARS-CoV-2 cell entry [ 14 , 15 ]. Besides, Nbs that target chemokines and cytokines can be customized to modify inflammation responses, which could be conducive to COVID-19 patients' recovery [ 16 ]. In this review, we elaborate on the use of nanobodies, a new type of recombinant antibody, as a treatment for COVID-19.…”

Study review of camelid and shark antibodies for biomedical and biotechnological applications

“…There is also a significant advance as a therapeutic agent, and even several VHH are in advanced clinical stages for use in humans. However, there are no studies that consider VHH in personalized medicine, such as tissue engineering 36 .…”