An intracellularly expressed Nsp9-specific nanobody in MARC-145 cells inhibits porcine reproductive and respiratory syndrome virus replication

Liu, Hongliang; Wang, Yan; Duan, Hong; Zhang, Angke; Liang, Chao; Gao, Jiming; Zhang, Chong; Huang, Baicheng; Li, Qiongyi; Li, Na; Xiao, Shuqi; Zhou, En‐Min

doi:10.1016/j.vetmic.2015.10.021

Cited by 67 publications

(73 citation statements)

References 31 publications

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“…In recent years, due to their unique properties and biocompatibility, especially non‐toxic metabolism, carbon nanomaterials including CDs,9,10,14,77 nanographene sheets,43,78 graphene quantum dots,13 have been extensively investigated and proved to have outstanding antiviral effects. They are prepared by polyglycerol, 4‐aminophenylboronic acid hydrochloride, benzoxazine, PEG‐diamine, 3‐ethoxypropylamine, curcumin, and other raw materials.…”

Section: Discussionmentioning

confidence: 99%

Glycyrrhizic‐Acid‐Based Carbon Dots with High Antiviral Activity by Multisite Inhibition Mechanisms

Tong

Zhou

et al. 2020

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With the gradual usage of carbon dots (CDs) in the area of antiviral research, attempts have been stepped up to develop new antiviral CDs with high biocompatibility and antiviral effects. In this study, a kind of highly biocompatible CDs (Gly‐CDs) is synthesized from active ingredient (glycyrrhizic acid) of Chinese herbal medicine by a hydrothermal method. Using the porcine reproductive and respiratory syndrome virus (PRRSV) as a model, it is found that the Gly‐CDs inhibit PRRSV proliferation by up to 5 orders of viral titers. Detailed investigations reveal that Gly‐CDs can inhibit PRRSV invasion and replication, stimulate antiviral innate immune responses, and inhibit the accumulation of intracellular reactive oxygen species (ROS) caused by PRRSV infection. Proteomics analysis demonstrates that Gly‐CDs can stimulate cells to regulate the expression of some host restriction factors, including DDX53 and NOS3, which are directly related to PRRSV proliferation. Moreover, it is found that Gly‐CDs also remarkably suppress the propagation of other viruses, such as pseudorabies virus (PRV) and porcine epidemic diarrhea virus (PEDV), suggesting the broad antiviral activity of Gly‐CDs. The integrated results demonstrate that Gly‐CDs possess extraordinary antiviral activity with multisite inhibition mechanisms, providing a promising candidate for alternative therapy for PRRSV infection.

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Section: Discussionmentioning

confidence: 99%

Glycyrrhizic‐Acid‐Based Carbon Dots with High Antiviral Activity by Multisite Inhibition Mechanisms

Tong

Zhou

et al. 2020

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“…So far, most nanobodies and cytosolic/nuclear nanobodies have been selected after immunization of llamas with the target protein. Nanobodies inhibited the function of HIV Rev, HIV Vpr, HIV‐1 Nef, influenza virus nucleoprotein, hepatitis B Core antigen (HBcAg), nonstructural proteins 9 and 4 of porcine reproductive and respiratory syndrome virus (PRRSV), p15 matrix protein of porcine endogenous retrovirus, SpvB toxin of Salmonella typhimurium , neurotoxine protease of Clostridium botulinum , mycotoxin 15‐Acetyldeoxynivalenol (15‐AcDON), protein kinase Cɛ, F‐actin capping protein CapG, L‐plastin, fascin and cortactin, gelsolin, β‐catenin, 2.5 dihydroxy pyridine dioxygenase (NicX), β 2 –adrenergic receptor, Nla protease of potato virus Y 78 and GFP for depletion of target GFP‐fusions in eukaryotics …”

Section: Strategies To Construct Camelid Vhh Repertoiresmentioning

confidence: 99%

“…The targets comprise intracellular enzymes including kinases: oncogenic proteins 56– toxins −55 proteins of the nervous system and virus proteins proteins from plants and drosophila – …”

Section: Introductionmentioning

confidence: 99%

Single domain antibodies for the knockdown of cytosolic and nuclear proteins

Böldicke

2017

Protein Science

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Single domain antibodies (sdAbs) from camels or sharks comprise only the variable heavy chain domain. Human sdAbs comprise the variable domain of the heavy chain (VH) or light chain (VL) and can be selected from human antibodies. SdAbs are stable, nonaggregating molecules in vitro and in vivo compared to complete antibodies and scFv fragments. They are excellent novel inhibitors of cytosolic/nuclear proteins because they are correctly folded inside the cytosol in contrast to scFv fragments. SdAbs are unique because of their excellent specificity and possibility to target posttranslational modifications such as phosphorylation sites, conformers or interaction regions of proteins that cannot be targeted with genetic knockout techniques and are impossible to knockdown with RNAi. The number of inhibiting cytosolic/nuclear sdAbs is increasing and usage of synthetic single pot single domain antibody libraries will boost the generation of these fascinating molecules without the need of immunization. The most frequently selected antigenic epitopes belong to viral and oncogenic proteins, followed by toxins, proteins of the nervous system as well as plant- and drosophila proteins. It is now possible to select functional sdAbs against virtually every cytosolic/nuclear protein and desired epitope. The development of new endosomal escape protein domains and cell-penetrating peptides for efficient transfection broaden the application of inhibiting sdAbs. Last but not least, the generation of relatively new cell-specific nanoparticles such as polymersomes and polyplexes carrying cytosolic/nuclear sdAb-DNA or -protein will pave the way to apply cytosolic/nuclear sdAbs for inhibition of viral infection and cancer in the clinic.

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“…Another nanobody NbMS10, which targets the MERS-CoV receptorbinding region significantly abrogates virus replication via its neutralization activity (Zhao et al, 2018). Further, Intracellularly-expressed Nb6 was found to potently suppress porcine reproductive and respiratory syndrome replication (Liu et al, 2015). Nevertheless, there have been no reports on the use of nanobodies for antiviral therapy against BVDV to date.…”

Section: Introductionmentioning

confidence: 99%

A novel intracellularly expressed NS5B-specific nanobody suppresses bovine viral diarrhea virus replication

Duan

et al. 2020

Veterinary Microbiology

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Bovine viral diarrhea virus (BVDV) infection causes significant economic losses to the cattle industry worldwide and still represents a huge pressure on agricultural production. Thus, the development of novel anti-BVDV strategies are urgently needed. The nonstructural protein 5 (NS5B) of BVDV is essential for viral replication. Further, the camel single-domain antibody (nanobody) represents a promising antiviral approach with the advantages of small size, stable structure, high specificity and solubility, and the recognition of specific epitopes. However, no NS5B-specific nanobodies against BVDV have been reported. In this study, NS5B-specific nanobodies were isolated from a phage display library of variable domains of Camellidae heavy chain-only antibodies (VHHs). Further, an MDBK cell line stably expressing Nb1 was established to explore antiviral activity. Results showed that Nb1 could markedly suppress BVDV replication and interact with the BVDV NS5B protein. This suggests that nanobodies have potential for the development of novel antiviral drugs against BVDV infection.

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An intracellularly expressed Nsp9-specific nanobody in MARC-145 cells inhibits porcine reproductive and respiratory syndrome virus replication

Cited by 67 publications

References 31 publications

Glycyrrhizic‐Acid‐Based Carbon Dots with High Antiviral Activity by Multisite Inhibition Mechanisms

Glycyrrhizic‐Acid‐Based Carbon Dots with High Antiviral Activity by Multisite Inhibition Mechanisms

Single domain antibodies for the knockdown of cytosolic and nuclear proteins

A novel intracellularly expressed NS5B-specific nanobody suppresses bovine viral diarrhea virus replication

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