scholarly journals 5．Confronting COVID-19： Current Issues of SARS-CoV-2 Therapeutic Drug/Vaccine Development

2021 ◽  
Vol 26 (1) ◽  
pp. 91-97
Author(s):  
Wataru SUGIURA
Keyword(s):  
Vaccine Development ◽  
Therapeutic Drug

scholarly journals A Chimeric Sudan Virus-Like Particle Vaccine Candidate Produced by a Recombinant Baculovirus System Induces Specific Immune Responses in Mice and Horses

Viruses ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 64 ◽  
Author(s):  
Fangfang Wu ◽  
Shengnan Zhang ◽  
Ying Zhang ◽  
Ruo Mo ◽  
Feihu Yan ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Ebola Virus ◽  
Vaccine Development ◽  
Recombinant Baculovirus ◽  
Neutralizing Antibody ◽  
Therapeutic Drug ◽  
Therapeutic Effects ◽  
Structural Protein ◽  
Virus Infections ◽  
Experimental Drugs

Ebola virus infections lead to severe hemorrhagic fevers in humans and nonhuman primates; and human fatality rates are as high as 67%–90%. Since the Ebola virus was discovered in 1976, the only available treatments have been medical support or the emergency administration of experimental drugs. The absence of licensed vaccines and drugs against the Ebola virus impedes the prevention of viral infection. In this study, we generated recombinant baculoviruses (rBV) expressing the Sudan virus (SUDV) matrix structural protein (VP40) (rBV-VP40-VP40) or the SUDV glycoprotein (GP) (rBV-GP-GP), and SUDV virus-like particles (VLPs) were produced by co-infection of Sf9 cells with rBV-SUDV-VP40 and rBV-SUDV-GP. The expression of SUDV VP40 and GP in SUDV VLPs was demonstrated by IFA and Western blot analysis. Electron microscopy results demonstrated that SUDV VLPs had a filamentous morphology. The immunogenicity of SUDV VLPs produced in insect cells was evaluated by the immunization of mice. The analysis of antibody responses showed that mice vaccinated with SUDV VLPs and the adjuvant Montanide ISA 201 produced SUDV GP-specific IgG antibodies. Sera from SUDV VLP-immunized mice were able to block infection by SUDV GP pseudotyped HIV, indicating that a neutralizing antibody against the SUDV GP protein was produced. Furthermore, the activation of B cells in the group immunized with VLPs mixed with Montanide ISA 201 was significant one week after the primary immunization. Vaccination with the SUDV VLPs markedly increased the frequency of antigen-specific cells secreting type 1 and type 2 cytokines. To study the therapeutic effects of SUDV antibodies, horses were immunized with SUDV VLPs emulsified in Freund’s complete adjuvant or Freund’s incomplete adjuvant. The results showed that horses could produce SUDV GP-specific antibodies and neutralizing antibodies. These results showed that SUDV VLPs demonstrate excellent immunogenicity and represent a promising approach for vaccine development against SUDV infection. Further, these horse anti-SUDV purified immunoglobulins lay a foundation for SUDV therapeutic drug research.

scholarly journals Implications for SARS-CoV-2 Vaccine Design: Fusion of Spike Glycoprotein Transmembrane Domain to Receptor-Binding Domain Induces Trimerization

Membranes ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 215 ◽  
Author(s):  
Taha Azad ◽  
Ragunath Singaravelu ◽  
Mathieu J.F. Crupi ◽  
Taylor Jamieson ◽  
Jaahnavi Dave ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Transmembrane Domain ◽  
Vaccine Development ◽  
Binding Domain ◽  
Effective Vaccine ◽  
Therapeutic Drug ◽  
Receptor Binding Domain ◽  
Design Strategies ◽  
Protein Receptor

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic presents an urgent need for an effective vaccine. Molecular characterization of SARS-CoV-2 is critical to the development of effective vaccine and therapeutic strategies. In the present study, we show that the fusion of the SARS-CoV-2 spike protein receptor-binding domain to its transmembrane domain is sufficient to mediate trimerization. Our findings may have implications for vaccine development and therapeutic drug design strategies targeting spike trimerization. As global efforts for developing SARS-CoV-2 vaccines are rapidly underway, we believe this observation is an important consideration for identifying crucial epitopes of SARS-CoV-2.

Tubulin structure at intermediate resolution

1995 ◽  
Vol 53 ◽  
pp. 852-853
Author(s):  
K. H. Downing ◽  
S. G. Wolf ◽  
E. Nogales
Keyword(s):  
High Resolution ◽  
Structural Data ◽  
Therapeutic Drug ◽  
Zinc Ions ◽  
Two Dimensional ◽  
X Ray Diffraction ◽  
X Ray ◽  
Negative Stain ◽  
Functional Mechanisms ◽  
Tubulin Structure

Microtubules are involved in a host of critical cell activities, many of which involve transport of organelles through the cell. Different sets of microtubules appear to form during the cell cycle for different functions. Knowledge of the structure of tubulin will be necessary in order to understand the various functional mechanisms of microtubule assemble, disassembly, and interaction with other molecules, but tubulin has so far resisted crystallization for x-ray diffraction studies. Fortuitously, in the presence of zinc ions, tubulin also forms two-dimensional, crystalline sheets that are ideally suited for study by electron microscopy. We have refined procedures for forming the sheets and preparing them for EM, and have been able to obtain high-resolution structural data that sheds light on the formation and stabilization of microtubules, and even the interaction with a therapeutic drug.Tubulin sheets had been extensively studied in negative stain, demonstrating that the same protofilament structure was formed in the sheets and microtubules. For high resolution studies, we have found that the sheets embedded in either glucose or tannin diffract to around 3 Å.

Diagnose und Monitoring bei chronisch-entzündlicher Darmerkrankung

2018 ◽  
Vol 75 (5) ◽  
pp. 316-328
Author(s):  
Christian Ansprenger ◽  
Emanuel Burri
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Morbus Crohn ◽  
Therapeutic Drug ◽  
Körperliche Untersuchung

Zusammenfassung. Die Diagnose und auch die Überwachung von chronisch entzündlichen Darmerkrankungen ruht auf mehreren Säulen: Anamnese, körperliche Untersuchung, Laborwerte (im Blut und Stuhl), Endoskopie, Histologie und Bildgebung. Die Diagnose kann nicht anhand eines einzelnen Befundes gestellt werden. In den letzten Jahren hat sich das Therapieziel weg von klinischen Endpunkten hin zu endoskopischen und sogar histologischen Endpunkten entwickelt. Für einige dieser neuen Therapieziele existiert allerdings noch keine allgemein gültige Definition. Regelmässige Endoskopien werden von Patienten schlecht toleriert, weshalb Surrogat-Marker wie Calprotectin untersucht wurden und eine gute Korrelation mit der mukosalen Entzündungsaktivität nachgewiesen werden konnte. Entsprechend zeigte sich bei Morbus Crohn eine Algorithmus-basierte Therapiesteuerung – unter anderem basierend auf Calprotectin – einer konventionellen Therapiesteuerung überlegen. Die Überwachung der medikamentösen Therapie («Therapeutic Drug Monitoring» [TDM]) ist ein zweites Standbein des Monitoring von chronisch entzündlichen Darmerkrankungen. Mit zunehmendem Einsatz vor allem der Biologika-Therapien wurden sowohl reaktives TDM (in Patienten mit klinischem Rezidiv) als auch proaktives TDM (in Patienten in Remission / stabiler Erkrankung) untersucht und haben (teilweise) Eingang in aktuelle Richtlinien gefunden. Zukünftige Studien werden die vorgeschlagenen Therapieziele besser definieren und den Nutzen der medikamentösen Therapieüberwachung auf den Krankheitsverlauf weiter untersuchen müssen.

Therapeutic drug monitoring (TDM) of the recent antipsychotic ziprasidone in dried blood spots (DBS) and plasma

2011 ◽  
Vol 44 (06) ◽  
Author(s):  
L Mercolini ◽  
G Fulgenzi ◽  
M Melis ◽  
G Boncompagni ◽  
LJ Albers ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Dried Blood Spots ◽  
Therapeutic Drug ◽  
Blood Spots

Comparison of CE and HPLC for therapeutic drug monitoring of the antiepileptic drug topiramate

2011 ◽  
Vol 44 (06) ◽  
Author(s):  
R Mandrioli ◽  
L Mercolini ◽  
N Ghedini ◽  
M Amore ◽  
E Kenndler ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Antiepileptic Drug ◽  
Drug Monitoring ◽  
Therapeutic Drug
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