scholarly journals Development of humanized tri-specific nanobodies with potent neutralization for SARS-CoV-2

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jianbo Dong ◽  
Betty Huang ◽  
Bo Wang ◽  
Allison Titong ◽  
Sachith Gallolu Kankanamalage ◽  
...  
Keyword(s):  
Computer Aided Design ◽  
Treatment Options ◽  
Unmet Need ◽  
Spike Protein ◽  
Therapeutic Antibodies ◽  
Human Igg1 ◽  
Vhh Antibodies ◽  
Phage Libraries ◽  
Aided Design ◽  
Potent Neutralization

Abstract SARS-CoV-2 is a newly emergent coronavirus, which has adversely impacted human health and has led to the COVID-19 pandemic. There is an unmet need to develop therapies against SARS-CoV-2 due to its severity and lack of treatment options. A promising approach to combat COVID-19 is through the neutralization of SARS-CoV-2 by therapeutic antibodies. Previously, we described a strategy to rapidly identify and generate llama nanobodies (VHH) from naïve and synthetic humanized VHH phage libraries that specifically bind the S1 SARS-CoV-2 spike protein, and block the interaction with the human ACE2 receptor. In this study we used computer-aided design to construct multi-specific VHH antibodies fused to human IgG1 Fc domains based on the epitope predictions for leading VHHs. The resulting tri-specific VHH-Fc antibodies show more potent S1 binding, S1/ACE2 blocking, and SARS-CoV-2 pseudovirus neutralization than the bi-specific VHH-Fcs or combination of individual monoclonal VHH-Fcs. Furthermore, protein stability analysis of the VHH-Fcs shows favorable developability features, which enable them to be quickly and successfully developed into therapeutics against COVID-19.

scholarly journals Development of humanized tri-specific nanobodies with potent neutralization for SARS-CoV-2

2020 ◽  
Author(s):  
Jianbo Dong ◽  
Betty Huang ◽  
Bo Wang ◽  
Allison Titong ◽  
Sachith Gallolu Kankanamalage ◽  
...  
Keyword(s):  
Treatment Options ◽  
Unmet Need ◽  
Spike Protein ◽  
Therapeutic Antibodies ◽  
Computer Aided ◽  
Human Igg1 ◽  
Vhh Antibodies ◽  
Phage Libraries ◽  
Potent Neutralization ◽  
Human Receptor

Abstract SARS-CoV-2 is a newly emergent coronavirus that causes COVID-19, which has adversely impacted human health and has led to a pandemic. There is an unmet need to develop therapies against SARS-CoV-2 due to its severity and lack of treatment options. A promising approach to combat COVID-19 is through the neutralization of SARS-CoV-2 by therapeutic antibodies. Previously, we described a strategy to rapidly identify and generate llama nanobodies (VHH) from naïve and synthetic humanized VHH phage libraries that specifically bind the S1 SARS-CoV-2 spike protein, and block the interaction to the ACE2 human receptor. In this study, we then used computer-aided designed and constructed multi-specific VHH antibodies fused to human IgG1 Fc domains based on the epitope predictions for leading VHHs. The resulting tri-specific VHH-Fc antibodies show more potent S1 binding, S1/ACE2 blocking, and SARS-CoV-2 pseudovirus neutralization than the bi-specific VHH-Fcs or combination of individual monoclonal VHH-Fcs. Furthermore, protein stability analysis of the VHH-Fcs show favorable developability features, which enable them to be quickly and successfully developed into therapeutics against COVID-19.

scholarly journals Managing Edentate Older Adults

2020 ◽  
Vol 9 (3) ◽  
pp. 29-33
Author(s):  
Murali Srinivasan ◽  
Martin Schimmel ◽  
Claudio Leles ◽  
Gerry McKenna
Keyword(s):  
Older Adults ◽  
Older People ◽  
Computer Aided Design ◽  
Treatment Options ◽  
Oral Rehabilitation ◽  
Cad Cam ◽  
Sizable Proportion ◽  
Natural Teeth ◽  
Number Of Treatment ◽  
Aided Design

Whilst increasing numbers of older people retain natural teeth, a sizable proportion of older people are still edentate. Replacement of missing teeth is important for function, aesthetics and to facilitate social interactions. The process of providing oral rehabilitation for edentate older adults can be challenging, but clinicians can utilise a number of treatment options including removable or implant retained prostheses. In this article, complete denture construction will be described using both conventional and copy denture techniques. Recent innovations in the process for constructing complete dentures using computer aided design and manufacturing (CAD-CAM) techniques will also be discussed. Dental implants can be used to help retain removable complete prostheses for edentate patients and the use of implant-retained overdentures is presented as a treatment alternative.

Optimal Sensor Design Using Patient-Specific Images

2010 ◽  
Vol 4 (2) ◽  
Author(s):  
Sukhi Basati ◽  
Timothy J. Harris ◽  
Andreas A. Linninger
Keyword(s):  
Computer Aided Design ◽  
Rational Design ◽  
Treatment Options ◽  
Patient Specific ◽  
Data Sets ◽  
Disease States ◽  
Magnetic Resonance Data ◽  
Computer Aided ◽  
Aided Design ◽  
Pathological Disease

In diseases such as hydrocephalus, the cerebral ventricles enlarge. The treatment options for these patients are presently based on pressure, which has limited capabilities. We present the design of a volume sensor as an alternative monitoring option. Through the use of computer aided design and simulation, we optimized a sensor in silico with fewer resources. Specifically, we designed a sensor for animal experimentation with a scalable procedure for human sensors. In this paper, we present a rational design approach for a sensor that integrates advances in medical imaging. Magnetic resonance data sets of both normal and diseased subjects were used as a virtual laboratory. Finite element simulations were performed under pathological disease states of the brain as a contribution toward an accelerated device design. An optimized sensor was then fabricated for these subjects based on the outcome of the simulations. In this paper, we explain how a computer aided subject-specific design was used to help fabricate and test our sensor.

scholarly journals Brace treatment for patients with scoliosis: State of the art

2021 ◽  
Vol 77 (2) ◽  
Author(s):  
Hans-Rudolf Weiss ◽  
Tuğba Kuru Çolak ◽  
Manuel Lay ◽  
Maksym Borysov
Keyword(s):  
Computer Aided Design ◽  
Scientific Literature ◽  
State Of The Art ◽  
Treatment Options ◽  
Success Rates ◽  
Physical Discomfort ◽  
Wide Range ◽  
Physical Distress ◽  
Aided Design ◽  
Made In

Background: Physiotherapy, brace applications or surgery are the treatment options utilised to manage patients with scoliosis. Many different brace applications are used, and the success rates of orthoses vary.Objectives: Brace applications can have detrimental impacts on the patient leading to physical discomfort, psychological discomfort, and in some instance the use of braces may even be painful. Therefore, future developments in this field should be aimed at improving the success rate and reducing physical distress experienced by the patient while using brace applications. The purpose of this article is to provide recommendations with respect to the most appropriate bracing approach in general.Method: A narrative review of the scientific literature was carried out to substantiate the statements made in this article.Results: The most important braces provided for the treatment of patients with scoliosis and the treatment results that can be achieved are presented and discussed, taking into account the most recent systematic reviews. A wide range of success rates have been found for the different brace applications.Conclusion: Given that brace application may impact the patient leading to physical discomfort and psychological distress, good quality management in brace application for patients with scoliosis is needed to ensure the best possible outcome and the least stressful management.Clinical implications: Safety in brace application for patients with scoliosis needs improvement. The use of standardised and reliable computer aided design (CAD) libraries and appropriate patient information based on published guidelines is suggested.

scholarly journals Optimization of Therapeutic Antibodies

2021 ◽  
Author(s):  
Bo Wang ◽  
Sachith Gallolu Kankanamalage ◽  
Jianbo Dong ◽  
Yue Liu
Keyword(s):  
Computer Aided Design ◽  
Therapeutic Antibody ◽  
Antigen Binding ◽  
Therapeutic Antibodies ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Successful Development ◽  
Physico Chemical ◽  
Display Technology ◽  
Site Mutagenesis ◽  
Aided Design

Abstract In this review, we have summarized the current landscape of therapeutic antibody optimization for successful development. By engineering antibodies with display technology, computer-aided design and site mutagenesis, various properties of the therapeutic antibody candidates can be improved with the purpose of enhancing their safety, efficacy and developability. These properties include antigen binding affinity and specificity, biological efficacy, pharmacokinetics and pharmacodynamics, immunogenicity, and physico-chemical developability features. A best-in-class strategy may require the optimization of all these properties to generate a good therapeutic antibody.

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