A potent neutralizing nanobody against SARS‐CoV‐2 with inhaled delivery potential

Gai, Junwei; Ma, Linlin; Li, Guanghui; Zhu, Min; Qiao, Peng; Li, Xiaofei; Zhang, Haiwei; Zhang, Yanmin; Chen, Yadong; Ji, Weiwei; Zhang, Hao; Cao, Hanwen; Li, Xionghui; Gong, Rui; Wan, Yakun

doi:10.1002/mco2.60

Cited by 79 publications

(61 citation statements)

References 33 publications

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“…Phage display has been one of the most powerful drug discovery technologies to lead to the development of FDA-approved peptide and antibody drugs for various diseases (e.g., hereditary angioedema, immune thrombocytopenic purpura, rheumatoid arthritis, and uveitis) [33,45,206] The success of phage display-derived drug molecules as well as the growing interest in peptides/antibodies in the biopharmaceutical market make phage display technology a popular approach for antiviral discovery. In fact, since the beginning of the latest coronavirus outbreak, several research groups have screened phage libraries to develop neutralizing recombinant antibodies against SARS-CoV-2 [83,191,[207][208][209][210][211][212].…”

Section: Perspectivementioning

confidence: 99%

Discovery of Antivirals Using Phage Display

Sokullu

Gauthier

Coulombe

2021

Viruses

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The latest coronavirus disease outbreak, COVID-19, has brought attention to viral infections which have posed serious health threats to humankind throughout history. The rapid global spread of COVID-19 is attributed to the increased human mobility of today’s world, yet the threat of viral infections to global public health is expected to increase continuously in part due to increasing human–animal interface. Development of antiviral agents is crucial to combat both existing and novel viral infections. Recently, there is a growing interest in peptide/protein-based drug molecules. Antibodies are becoming especially predominant in the drug market. Indeed, in a remarkably short period, four antibody therapeutics were authorized for emergency use in COVID-19 treatment in the US, Russia, and India as of November 2020. Phage display has been one of the most widely used screening methods for peptide/antibody drug discovery. Several phage display-derived biologics are already in the market, and the expiration of intellectual property rights of phage-display antibody discovery platforms suggests an increment in antibody drugs in the near future. This review summarizes the most common phage display libraries used in antiviral discovery, highlights the approaches employed to enhance the antiviral potency of selected peptides/antibody fragments, and finally provides a discussion about the present status of the developed antivirals in clinic.

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Section: Perspectivementioning

confidence: 99%

Discovery of Antivirals Using Phage Display

Sokullu

Gauthier

Coulombe

2021

Viruses

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“…Neutralized monoclonal antibody AR-711 has been explored as inhaled, self-administered therapy for mild to moderate COVID-19 patients to inhibit the receptor-binding domain (RBD) of the SARS-CoV2 virus and its constantly evolving variants [9]. Nanobodies (Nb) are antibody-like molecules discovered from the blood of camels [22]. Nanobodies (Nb) have been shown to block the binding between the SARS-CoV-2-RBD variants to the ACE2 (angiotensin-converting enzyme 2) receptor.…”

Section: Inhaled Vaccinesmentioning

confidence: 99%

“…Nanobodies (Nb) have been shown to block the binding between the SARS-CoV-2-RBD variants to the ACE2 (angiotensin-converting enzyme 2) receptor. In particular, Nb11-59 can be a potent preventative and therapeutic agent against COVID-19, especially through inhalation delivery [22]. Inhaled ciclesonide also shows strong antiviral actions against SARS-COV-2 and is promising to prevent virally induced lung injuries in the alveolar region [23,24].…”

Section: Inhaled Vaccinesmentioning

confidence: 99%

Lung Physiological Variations in COVID-19 Patients and Inhalation Therapy Development for Remodeled Lungs

Walfield

April

et al. 2021

SciMed. J.

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In response to the unmet need for effective treatments for symptomatic patients, research efforts of inhaled therapy for COVID-19 patients have been pursued since the pandemic began. However, inhalation drug delivery to the lungs is sensitive to the lung anatomy and physiology, which can be significantly altered due to the viral infection. The ensued ventilation heterogeneity will change distribution and thus dosimetry of inhaled medications, rendering previous correlations concepts? of pulmonary drug delivery in healthy lungs less reliable. In this study, we first reviewed the recent developments of inhaled therapeutics and vaccines, as well as the latest knowledge of the lung structural variations documented by CT of COVID-19 patients' lungs. We then quantified the volume ratios of the poorly aerated lungs and non-aerated lungs in eight COVID-19 patients, which ranged 2-8% and 0.5-3%, respectively. The need to consider the diseased lung physiologies in estimating pulmonary delivery was emphasized. Diseased lung geometries with varying lesion sites and complexities were reconstructed using Statistical Shape Modeling (SSM). A new segmentation method was applied that could generate patient-specific lung geometries with an increased number of branching generations. The synergy of the CT-based lung segmentation and SSM-based airway variation showed promise for developing representative COVID-infected lung morphological models and investigating inhalation therapeutics in COVID-19 patients. Doi: 10.28991/SciMedJ-2021-0303-1 Full Text: PDF

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“… Potent neutralizing ability against authentic SARS-CoV-2 in the Plaque Reduction Neutralization Test (PRNT) at the concentration of 50 and 5 μg/ml Good stability profile which was not impacted by nebulization. [ 48 ] 2 Sybody Synthetic E. coli RBD Six Sybodies can bind to the viral spike protein with double-digit nanomolar affinity Five Sybodies showed substantial inhibition of RBD interaction with ACE2 Binding small antiviral molecules to the Sybody can increase their antiviral potency due to recognizing secondary epitopes of the virus. [ 49 ] 3 Monovalent Fc conjugated (Nanosota-1C-Fc) Naïve library from llamas and alpacas E. coli RBD Tightly bound to the SARS-CoV-2 RBD and completely blocked out ACE2 (Kd = 15.7 pM) Potently neutralized SARS-CoV-2 pseudovirus entry and authentic infection.…”

Section: Nanobodies Application Against Viral Infections Including Sars-cov-2mentioning

confidence: 99%

Nanobodies as powerful pulmonary targeted biotherapeutics against SARS-CoV-2, pharmaceutical point of view

Najmeddin

Shapourabadi²,

Behdani

et al. 2021

Biochimica et Biophysica Acta (BBA) - General Subjects

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Background Since December 2019, the newly emerged SARS-CoV-2 virus continues to infect humans and many people died from severe Covid-19 during the last 2 years worldwide. Different approaches are being used for treatment of this infection and its consequences, but limited results have been achieved and new therapeutics are still needed. One of the most interesting biotherapeutics in this era are Nanobodies which have shown very promising results in recent researches. Scope of review Here, we have reviewed the potentials of Nanobodies in Covid-19 treatment. We have also discussed the properties of these biotherapeutics that make them very suitable for pulmonary drug delivery, which seems to be very important route of administration in this disease. Major conclusion Nanobodies with their special biological and biophysical characteristics and their resistance against harsh manufacturing condition, can be considered as promising, targeted biotherapeutics which can be administered by pulmonary delivery pharmaceutical systems against Covid-19. General significance Covid-19 has become a global problem during the last two years and with emerging mutant strains, prophylactic and therapeutic approaches are still highly needed. Nanobodies with their specific properties can be considered as valuable and promising candidates in Covid-19 therapy.

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A potent neutralizing nanobody against SARS‐CoV‐2 with inhaled delivery potential

Cited by 79 publications

References 33 publications

Discovery of Antivirals Using Phage Display

Discovery of Antivirals Using Phage Display

Lung Physiological Variations in COVID-19 Patients and Inhalation Therapy Development for Remodeled Lungs

Nanobodies as powerful pulmonary targeted biotherapeutics against SARS-CoV-2, pharmaceutical point of view

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