Outlook of therapeutic and diagnostic competency of nanobodies against SARS-CoV-2: A systematic review

Aria, Hamid; Mahmoodi, Fatemeh; Ghaheh, Hooria Seyedhosseini; mavandadnejad, Faranak; Zare, Hamed; Heiat, Mohammad; Bakherad, Hamid

doi:10.1016/j.ab.2022.114546

Cited by 24 publications

(19 citation statements)

References 61 publications

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“…Nanobodies or single-domain antibodies provide important advantages over traditional antibodies, including their smaller size and robust biochemical properties such as high thermal stability, high solubility, and ability to be bioengineered into novel multivalent, multi-specific, and high-affinity molecules, making them a class of emerging powerful therapies against SARS-CoV-2 [36][37][38][39][40][41]. Recent research efforts in the design, engineering, and structure-functional characterization of nanobodies and their binding with SARS-CoV-2 S proteins reflect a growing realization that nanobody combinations could deliver a powerful array of neutralizing and escape mutation resistant molecular assemblies capable of rationally exploiting distinct binding epitopes and the intrinsic plasticity of the SARS-CoV-2 S protein.…”

Section: Introductionmentioning

confidence: 99%

Allosteric Determinants of the SARS-CoV-2 Spike Protein Binding with Nanobodies: Examining Mechanisms of Mutational Escape and Sensitivity of the Omicron Variant

Verkhivker

2022

IJMS

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Structural and biochemical studies have recently revealed a range of rationally engineered nanobodies with efficient neutralizing capacity against the SARS-CoV-2 virus and resilience against mutational escape. In this study, we performed a comprehensive computational analysis of the SARS-CoV-2 spike trimer complexes with single nanobodies Nb6, VHH E, and complex with VHH E/VHH V nanobody combination. We combined coarse-grained and all-atom molecular simulations and collective dynamics analysis with binding free energy scanning, perturbation-response scanning, and network centrality analysis to examine mechanisms of nanobody-induced allosteric modulation and cooperativity in the SARS-CoV-2 spike trimer complexes with these nanobodies. By quantifying energetic and allosteric determinants of the SARS-CoV-2 spike protein binding with nanobodies, we also examined nanobody-induced modulation of escaping mutations and the effect of the Omicron variant on nanobody binding. The mutational scanning analysis supported the notion that E484A mutation can have a significant detrimental effect on nanobody binding and result in Omicron-induced escape from nanobody neutralization. Our findings showed that SARS-CoV-2 spike protein might exploit the plasticity of specific allosteric hotspots to generate escape mutants that alter response to binding without compromising activity. The network analysis supported these findings showing that VHH E/VHH V nanobody binding can induce long-range couplings between the cryptic binding epitope and ACE2-binding site through a broader ensemble of communication paths that is less dependent on specific mediating centers and therefore may be less sensitive to mutational perturbations of functional residues. The results suggest that binding affinity and long-range communications of the SARS-CoV-2 complexes with nanobodies can be determined by structurally stable regulatory centers and conformationally adaptable hotspots that are allosterically coupled and collectively control resilience to mutational escape.

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Section: Introductionmentioning

confidence: 99%

Allosteric Determinants of the SARS-CoV-2 Spike Protein Binding with Nanobodies: Examining Mechanisms of Mutational Escape and Sensitivity of the Omicron Variant

Verkhivker

2022

IJMS

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“…However, nanobodies have some disadvantages, including rapid renal clearance and induced nephrotoxicity [ 52 ]. In the diagnosis application of nanobodies, these disadvantages are not troublesome, but these defects can be problematic in therapeutic application.…”

Section: Discussionmentioning

confidence: 99%

Nanobodies; new molecular instruments with special specifications for targeting, diagnosis and treatment of triple-negative breast cancer

et al. 2022

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Breast cancer is the most common type of cancer in women and the second leading cause of cancer death in female. Triple-negative breast cancer has a more aggressive proliferation and a poorer clinical diagnosis than other breast cancers. The most common treatments for TNBC are chemotherapy, surgical removal, and radiation therapy, which impose many side effects and costs on patients. Nanobodies have superior advantages, which makes them attractive for use in therapeutic agents and diagnostic kits. There are numerous techniques suggested by investigators for early detection of breast cancer. Nevertheless, there are fewer molecular diagnostic methods in the case of TNBC due to the lack of expression of famous breast cancer antigens in TNBC. Although conventional antibodies have a high ability to detect tumor cell markers, their large size, instability, and costly production cause a lot of problems. Since the HER-2 do not express in TNBC diagnosis, the production of nanobodies for the diagnosis and treatment of cancer cells should be performed against other antigens expressed in TNBC. In this review, nanobodies which developed against triple negative breast cancer, were classified based on type of antigen.

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“…Newer biological products such as nanobodies may prove to be useful, but like many therapeutics, their role will need to investigated in patients suffering from the omicron variant. Detailed discussion of nanobodies [ 102 ] is beyond the scope of this article, which aims to provide an overview of the current status of human antibodies in COVID-19.…”

Section: Limited Therapeutic and Protective Role Of Sars-cov-2 Antibo...mentioning

confidence: 99%

The (apparent) antibody paradox in COVID-19

Ameratunga

Woon

Lea

et al. 2022

Expert Review of Clinical Immunology

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Introduction The immunological response to COVID-19 is only partly understood. It is increasingly clear that the virus triggers an inappropriate host inflammatory reaction in patients experiencing severe disease. Areas covered The role of antibodies in COVID-19 remains to be fully defined. There is evidence for both protection and harm in different clinical syndromes triggered by SARS-CoV-2. Many patients dying from COVID-19 had both high titers of antibodies to SARS-CoV-2 and elevated viral loads. The uncertain protective role of humoral immunity is mirrored by the lack of benefit of therapeutic convalescent plasma infusions in COVID-19. In contrast, there is increasing evidence that a vigorous T-cell response is protective. Delayed or low avidity T cell reactions were seen in patients suffering severe COVID-19. Expert opinion These observations suggest T cell responses to SARS-CoV-2 are the dominant long-term protective mechanism following either infection or vaccination. The magnitude and quality of the antibody response is likely to reflect underlying T cell immunity to SARS-CoV-2. Much of what has been learned about COVID-19 will need to be revised following the recent rapid emergence and dominance of the omicron variant of SARS-CoV-2.

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Outlook of therapeutic and diagnostic competency of nanobodies against SARS-CoV-2: A systematic review

Cited by 24 publications

References 61 publications

Allosteric Determinants of the SARS-CoV-2 Spike Protein Binding with Nanobodies: Examining Mechanisms of Mutational Escape and Sensitivity of the Omicron Variant

Allosteric Determinants of the SARS-CoV-2 Spike Protein Binding with Nanobodies: Examining Mechanisms of Mutational Escape and Sensitivity of the Omicron Variant

Nanobodies; new molecular instruments with special specifications for targeting, diagnosis and treatment of triple-negative breast cancer

The (apparent) antibody paradox in COVID-19

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