The Potential of Nanobodies for COVID-19 Diagnostics and Therapeutics

Abstract

The infectious severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent for coronavirus disease 2019 (COVID-19). Globally, there have been millions of infections and fatalities. Unfortunately, the virus has been persistent and a contributing factor is the emergence of several variants. The urgency to combat COVID-19 led to the identification/development of various diagnosis (polymerase chain reaction and antigen tests) and treatment (repurposed drugs, convalescent plasma, antibodies and vaccines) options. These treatments may treat mild symptoms and decrease the risk of life-threatening disease. Although these options have been fairly beneficial, there are some challenges and limitations, such as cost of tests/drugs, specificity, large treatment dosages, intravenous administration, need for trained personal, lengthy production time, high manufacturing costs, and limited availability. Therefore, the development of more efficient COVID-19 diagnostic and therapeutic options are vital. Nanobodies (Nbs) are novel monomeric antigen-binding fragments derived from camelid antibodies. Advantages of Nbs include low immunogenicity, high specificity, stability and affinity. These characteristics allow for rapid Nb generation, inexpensive large-scale production, effective storage, and transportation, which is essential during pandemics. Additionally, the potential aerosolization and inhalation delivery of Nbs allows for targeted treatment delivery as well as patient self-administration. Therefore, Nbs are a viable option to target SARS-CoV-2 and overcome COVID-19. In this review we discuss (1) COVID-19; (2) SARS-CoV-2; (3) the present conventional COVID-19 diagnostics and therapeutics, including their challenges and limitations; (4) advantages of Nbs; and (5) the numerous Nbs generated against SARS-CoV-2 as well as their diagnostic and therapeutic potential.

Nanobodies against SARS-CoV-2 reduced virus load in the brain of challenged mice and neutralized Wuhan, Delta and Omicron Variants

“…This was achieved through biopanning of existing libraries for MERS and SARS coronavirus or immunizing llamas and alpacas with multiple SARS-CoV-2 antigens, primarily S and RBD recombinant proteins [28–37] . So far, several Nbs have been developed with promising diagnostic and therapeutic applications [20,38]. Both monomeric Nbs and engineered molecules showed strong neutralizing activity to the different VOCs that have emerged, including the Omicron variants [39–46].…”

“…One concern about employing mAbs therapies is that the emergence of new variants, such as the Omicron, are often unaffected by their use [17–19]. For this reason, other passive immunization strategies, such as the use of llama-derived nanobodies (Nbs), are an attractive alternative to develop highly sensitive diagnostic methods, and contribute to the preventive and therapeutic treatment of the disease [20].…”

Interaction of SARS-CoV-2 with host cells and antibodies: experiment and simulation

“…8 Since the beginning of the pandemic, the research community has made tremendous efforts to find effective treatments for COVID-19. Despite the great success of current vaccines, in particular mRNA vaccines, 9 antibodies 10,11 and drugs such as Remdesivir, Molnupiravir and Paxlovid [12][13][14][15] the fight against SARS-CoV-2 continues as more and more variants of concern such as Omicron emerge. The pandemic has gone through several waves, 16,17 with first, second and third waves caused by an ancestral strain from Wuhan, Beta, and Delta variants, 18 respectively.…”

Streamlined Specimen Purification for Rapid COVID-19 Diagnosis Using Positively Charged Polymer Thin Film-Coated Surfaces and Chamber Digital PCR

“…The gold standard diagnostic technique for SARS-CoV-2 is the real-time reverse transcriptase polymerase chain reaction (RT-PCR). It involves the collection of a specimen from the patient’s upper respiratory tract using a swab, viral inactivation, RNA isolation, and RNA amplification. , PCR-based diagnostics allow for the detection of viral RNA fragments with high specificity and sensitivity. , …”

“…9,10 PCR-based diagnostics allow for the detection of viral RNA fragments with high specificity and sensitivity. 11,12 However, RNA extraction is a complex, time-consuming, and multistep (lysing, binding, washing, and elution) process. In addition, it needs to be performed by experts with extensive experience; thus, RNA-based diagnosis is costly and has a long turnaround time, which hinders its diagnostic efficiency.…”