Pub Date : 2022-07-03DOI: 10.1080/0889311x.2022.2123916
N. Anuar, Siti Nurul’ain Yusop, K. Roberts
The fundamental crystal science underpinning the industrial crystallisation of organic materials is reviewed from molecular, intermolecular (synthonic) and crystallographic perspectives. The main aspects that differentiate the crystal growth of these materials from more conventional commercial crystal growth of large single crystals and epitaxial layers for micro-electronic applications are highlighted. Building up on key concepts of intermolecular forces, crystallisation and crystal chemistry, the factors that govern the bulk structure, equilibrium external morphology and hence surface chemistry of crystals are reviewed. The non-equilibrium case of solution-phase crystallisation builds upon this, dealing with the core aspects of solubility, solution metastability, and hence crystallisability and how supersaturation relates to molecular assembly through the nucleation process and the subsequent faceting of the nuclei through the growth process into well-defined polyhedral crystalline forms. The practical implications are brought into sharp focus through a number of case-study examples whereby the crystallisation process can be engineered to produce crystals with pre- desired physico-chemical properties, notably crystal size, crystal structure, crystal morphology, purity and agglomerability. Abbreviations: 0D: Zero-dimension; 1D: One-dimension; 2D: Two-dimension; 3D: Three-dimension; ADDoPT: Advanced Digital Design Transforming Pharmaceutical Development and Manufacture; AE: Attachment energy; AFM: Atomic force microscopic; AIDS: Acquired Immuno-Deficiency Syndrome; API: Active Pharmaceutical Ingredient; ATR-FTIR: Attenuated total reflectance – Fourier transform infrared; B&S: Birth & Spread; BCF: Burton-Cabrera-Frank; BFDH: Bravais–Friedel–Donnay–Harker; Bud: Budesonide; CCDC: Cambridge Crystallographic Data Centre; CSD: Crystal size distribution; DSC: Differential scanning calorimetry; EPSRC: Engineering and Physical Sciences Research Council; EtOH: Ethanol; F: Flat faces; FP: Fluticasone propionate; FTIR: Fourier transform infrared; H-bonding: Hydrogen bonding; IN: Instantaneous nucleation; ISSCG-17: The 17th International Summer School on Crystal Growth; K: Kink faces; KBHR: Kashchiev – Borissova – Hammond – Roberts; KJR: Kevin J Roberts; LGA: L-glutamic acid; MCS: Manufacturing Classification System; MSG: Monosodium glutamate; MSZW: Metastable zone width; NA: Nornizar Anuar; PABA: Para-amino benzoic acid; PBC: Periodic Bond Chain; PN: Progressive nucleation; PXRD: Powder x-ray diffraction; R&D: Research and Development; RIG: Rough interface growth; ROY: Red-Orange-Yellow; S: Stepped faces; SB: Salbutamol; SDS: Sodium dodecyl sulphate; UiTM: Universiti Teknologi MARA; UV-Vis: Ultraviolet–visible spectroscopy; XRD: X-ray diffraction
{"title":"Crystallisation of organic materials from the solution phase: a molecular, synthonic and crystallographic perspective","authors":"N. Anuar, Siti Nurul’ain Yusop, K. Roberts","doi":"10.1080/0889311x.2022.2123916","DOIUrl":"https://doi.org/10.1080/0889311x.2022.2123916","url":null,"abstract":"The fundamental crystal science underpinning the industrial crystallisation of organic materials is reviewed from molecular, intermolecular (synthonic) and crystallographic perspectives. The main aspects that differentiate the crystal growth of these materials from more conventional commercial crystal growth of large single crystals and epitaxial layers for micro-electronic applications are highlighted. Building up on key concepts of intermolecular forces, crystallisation and crystal chemistry, the factors that govern the bulk structure, equilibrium external morphology and hence surface chemistry of crystals are reviewed. The non-equilibrium case of solution-phase crystallisation builds upon this, dealing with the core aspects of solubility, solution metastability, and hence crystallisability and how supersaturation relates to molecular assembly through the nucleation process and the subsequent faceting of the nuclei through the growth process into well-defined polyhedral crystalline forms. The practical implications are brought into sharp focus through a number of case-study examples whereby the crystallisation process can be engineered to produce crystals with pre- desired physico-chemical properties, notably crystal size, crystal structure, crystal morphology, purity and agglomerability. Abbreviations: 0D: Zero-dimension; 1D: One-dimension; 2D: Two-dimension; 3D: Three-dimension; ADDoPT: Advanced Digital Design Transforming Pharmaceutical Development and Manufacture; AE: Attachment energy; AFM: Atomic force microscopic; AIDS: Acquired Immuno-Deficiency Syndrome; API: Active Pharmaceutical Ingredient; ATR-FTIR: Attenuated total reflectance – Fourier transform infrared; B&S: Birth & Spread; BCF: Burton-Cabrera-Frank; BFDH: Bravais–Friedel–Donnay–Harker; Bud: Budesonide; CCDC: Cambridge Crystallographic Data Centre; CSD: Crystal size distribution; DSC: Differential scanning calorimetry; EPSRC: Engineering and Physical Sciences Research Council; EtOH: Ethanol; F: Flat faces; FP: Fluticasone propionate; FTIR: Fourier transform infrared; H-bonding: Hydrogen bonding; IN: Instantaneous nucleation; ISSCG-17: The 17th International Summer School on Crystal Growth; K: Kink faces; KBHR: Kashchiev – Borissova – Hammond – Roberts; KJR: Kevin J Roberts; LGA: L-glutamic acid; MCS: Manufacturing Classification System; MSG: Monosodium glutamate; MSZW: Metastable zone width; NA: Nornizar Anuar; PABA: Para-amino benzoic acid; PBC: Periodic Bond Chain; PN: Progressive nucleation; PXRD: Powder x-ray diffraction; R&D: Research and Development; RIG: Rough interface growth; ROY: Red-Orange-Yellow; S: Stepped faces; SB: Salbutamol; SDS: Sodium dodecyl sulphate; UiTM: Universiti Teknologi MARA; UV-Vis: Ultraviolet–visible spectroscopy; XRD: X-ray diffraction","PeriodicalId":54385,"journal":{"name":"Crystallography Reviews","volume":"28 1","pages":"97 - 215"},"PeriodicalIF":3.0,"publicationDate":"2022-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49232182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-07-03DOI: 10.1080/0889311X.2022.2130587
P. Bombicz
The article starts with a timeline of important discoveries in the field of inclusion compounds, together with other significant related events including their references. The article finishes with the list of meetings, which deal with various aspects of inclusion compounds. These historical overviews already enlighten, why on the one hand it is important for students and professors to have this article in their collection. On the other hand, the review presents in detail the structural features and physicochemical properties of solid inclusion compounds and the complementary analytical techniques used for their investigation. The composition and stoichiometry of inclusion compounds are not neces-sarily invariant, they depend on the synthetic method, the solvent used, the temperature of crystallization, the pressure during the synthesis if it is performed in a sealed container, decomposi-tion ‘Crystallisation of organic materials from the solution phase: a molecular, synthonic and crystallographic perspective’ is a must read for everyone who has ever or will deal with crystallization of organic materials in theory or practice, in academia or industry. The article presents a holistic approach of crystallization based on the material science tetra-hedron concept attentive to the interdependent relationship between material structure, properties, performance and processing. First, we get familiar with the key factors related to the crystal structure: molecular structure, intermolecular interactions, synthon formation, polymorphism, lattice energy, crystal morphology and surface chemistry. Then the crystallization process is described from nucleation to crystal growth detailing the role of solubility, supersaturation and solute clastering; followed by stages of the crystal growth process and nature of the crystal/solution interface, the crystal growth mechanisms and growth stability. The last chapter is dedicated to the product design through the crystallization process design by selected examples of compounds, to the control of crystallinity and polymorphic form, crystal size and morphology, crystal purity and agglomeration. The review provides a knowledge route-map of crystallization of organic materials along with case studies proving how the crystallization process can be manipulated to produce crystalline materials with targeted physical–chemical properties. published by Springer Nature Singapore in 2019. The volume covers the wide variety of compounds isolated from different plants used in the treatment of various diseases like inflammation, diabetes, malaria, cancer, hormonal problems, cardiovascular or kidney diseases. It provides an overview of compound groups that have good bioactivity and details the reaction mechanism to the intended target and can be used as an illus-tration of the development of bioactive compounds in the future, and especially the role of crystallography in drug design. The book discusses chemical structures, informati
{"title":"Crystallization: from molecules to crystal structures","authors":"P. Bombicz","doi":"10.1080/0889311X.2022.2130587","DOIUrl":"https://doi.org/10.1080/0889311X.2022.2130587","url":null,"abstract":"The article starts with a timeline of important discoveries in the field of inclusion compounds, together with other significant related events including their references. The article finishes with the list of meetings, which deal with various aspects of inclusion compounds. These historical overviews already enlighten, why on the one hand it is important for students and professors to have this article in their collection. On the other hand, the review presents in detail the structural features and physicochemical properties of solid inclusion compounds and the complementary analytical techniques used for their investigation. The composition and stoichiometry of inclusion compounds are not neces-sarily invariant, they depend on the synthetic method, the solvent used, the temperature of crystallization, the pressure during the synthesis if it is performed in a sealed container, decomposi-tion ‘Crystallisation of organic materials from the solution phase: a molecular, synthonic and crystallographic perspective’ is a must read for everyone who has ever or will deal with crystallization of organic materials in theory or practice, in academia or industry. The article presents a holistic approach of crystallization based on the material science tetra-hedron concept attentive to the interdependent relationship between material structure, properties, performance and processing. First, we get familiar with the key factors related to the crystal structure: molecular structure, intermolecular interactions, synthon formation, polymorphism, lattice energy, crystal morphology and surface chemistry. Then the crystallization process is described from nucleation to crystal growth detailing the role of solubility, supersaturation and solute clastering; followed by stages of the crystal growth process and nature of the crystal/solution interface, the crystal growth mechanisms and growth stability. The last chapter is dedicated to the product design through the crystallization process design by selected examples of compounds, to the control of crystallinity and polymorphic form, crystal size and morphology, crystal purity and agglomeration. The review provides a knowledge route-map of crystallization of organic materials along with case studies proving how the crystallization process can be manipulated to produce crystalline materials with targeted physical–chemical properties. published by Springer Nature Singapore in 2019. The volume covers the wide variety of compounds isolated from different plants used in the treatment of various diseases like inflammation, diabetes, malaria, cancer, hormonal problems, cardiovascular or kidney diseases. It provides an overview of compound groups that have good bioactivity and details the reaction mechanism to the intended target and can be used as an illus-tration of the development of bioactive compounds in the future, and especially the role of crystallography in drug design. The book discusses chemical structures, informati","PeriodicalId":54385,"journal":{"name":"Crystallography Reviews","volume":"28 1","pages":"67 - 69"},"PeriodicalIF":3.0,"publicationDate":"2022-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45472508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-06-01Epub Date: 2022-05-16DOI: 10.2217/cns-2022-0005
John de Groot, Martina Ott, Jun Wei, Cynthia Kassab, Dexing Fang, Hinda Najem, Barbara O'Brien, Shiao-Pei Weathers, Carlos Kamiya Matsouka, Nazanin K Majd, Rebecca A Harrison, Gregory N Fuller, Jason T Huse, James P Long, Raymond Sawaya, Ganesh Rao, Tobey J MacDonald, Waldemar Priebe, Michael DeCuypere, Amy B Heimberger
Aim: To ascertain the maximum tolerated dose (MTD)/maximum feasible dose (MFD) of WP1066 and p-STAT3 target engagement within recurrent glioblastoma (GBM) patients. Patients & methods: In a first-in-human open-label, single-center, single-arm 3 + 3 design Phase I clinical trial, eight patients were treated with WP1066 until disease progression or unacceptable toxicities. Results: In the absence of significant toxicity, the MFD was identified to be 8 mg/kg. The most common adverse event was grade 1 nausea and diarrhea in 50% of patients. No treatment-related deaths occurred; 6 of 8 patients died from disease progression and one was lost to follow-up. Of 8 patients with radiographic follow-up, all had progressive disease. The longest response duration exceeded 3.25 months. The median progression-free survival (PFS) time was 2.3 months (95% CI: 1.7 months-NA months), and 6-month PFS (PFS6) rate was 0%. The median overall survival (OS) rate was 25 months (95% CI: 22.5 months-NA months), with an estimated 1-year OS rate of 100%. Pharmacokinetic (PK) data demonstrated that at 8 mg/kg, the T1/2 was 2-3 h with a dose dependent increase in the Cmax. Immune monitoring of the peripheral blood demonstrated that there was p-STAT3 suppression starting at a dose of 1 mg/kg. Conclusion: Immune analyses indicated that WP1066 inhibited systemic immune p-STAT3. WP1066 had an MFD identified at 8 mg/kg which is the target allometric dose based on prior preclinical modeling in combination with radiation therapy and a Phase II study is being planned for newly diagnosed MGMT promoter unmethylated glioblastoma patients.
{"title":"A first-in-human Phase I trial of the oral p-STAT3 inhibitor WP1066 in patients with recurrent malignant glioma.","authors":"John de Groot, Martina Ott, Jun Wei, Cynthia Kassab, Dexing Fang, Hinda Najem, Barbara O'Brien, Shiao-Pei Weathers, Carlos Kamiya Matsouka, Nazanin K Majd, Rebecca A Harrison, Gregory N Fuller, Jason T Huse, James P Long, Raymond Sawaya, Ganesh Rao, Tobey J MacDonald, Waldemar Priebe, Michael DeCuypere, Amy B Heimberger","doi":"10.2217/cns-2022-0005","DOIUrl":"10.2217/cns-2022-0005","url":null,"abstract":"<p><p><b>Aim:</b> To ascertain the maximum tolerated dose (MTD)/maximum feasible dose (MFD) of WP1066 and p-STAT3 target engagement within recurrent glioblastoma (GBM) patients. <b>Patients & methods:</b> In a first-in-human open-label, single-center, single-arm 3 + 3 design Phase I clinical trial, eight patients were treated with WP1066 until disease progression or unacceptable toxicities. <b>Results:</b> In the absence of significant toxicity, the MFD was identified to be 8 mg/kg. The most common adverse event was grade 1 nausea and diarrhea in 50% of patients. No treatment-related deaths occurred; 6 of 8 patients died from disease progression and one was lost to follow-up. Of 8 patients with radiographic follow-up, all had progressive disease. The longest response duration exceeded 3.25 months. The median progression-free survival (PFS) time was 2.3 months (95% CI: 1.7 months-NA months), and 6-month PFS (PFS6) rate was 0%. The median overall survival (OS) rate was 25 months (95% CI: 22.5 months-NA months), with an estimated 1-year OS rate of 100%. Pharmacokinetic (PK) data demonstrated that at 8 mg/kg, the T<sub>1/2</sub> was 2-3 h with a dose dependent increase in the C<sub>max</sub>. Immune monitoring of the peripheral blood demonstrated that there was p-STAT3 suppression starting at a dose of 1 mg/kg. <b>Conclusion:</b> Immune analyses indicated that WP1066 inhibited systemic immune p-STAT3. WP1066 had an MFD identified at 8 mg/kg which is the target allometric dose based on prior preclinical modeling in combination with radiation therapy and a Phase II study is being planned for newly diagnosed MGMT promoter unmethylated glioblastoma patients.</p>","PeriodicalId":54385,"journal":{"name":"Crystallography Reviews","volume":"18 1","pages":"CNS87"},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82007685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-13DOI: 10.1080/0889311X.2022.2074413
Siska Elisahbet Sinaga, U. Supratman, T. Mayanti
{"title":"Natural Bioactive Compounds: Volume 2 Chemistry, Pharmacology, and Health Care Practices","authors":"Siska Elisahbet Sinaga, U. Supratman, T. Mayanti","doi":"10.1080/0889311X.2022.2074413","DOIUrl":"https://doi.org/10.1080/0889311X.2022.2074413","url":null,"abstract":"","PeriodicalId":54385,"journal":{"name":"Crystallography Reviews","volume":"28 1","pages":"216 - 219"},"PeriodicalIF":3.0,"publicationDate":"2022-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47981884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-07DOI: 10.1080/0889311X.2022.2067849
L. Nassimbeni, Nicole M. Sykes
The physicochemical properties of Inclusion Compounds are described in terms of structure, selectivity, kinetics of decomposition, and enclathration. Their formation and stability are dependent on the phenomenon of molecular recognition. Thus, their thermal behaviour results from the secondary interactions which occur in the various molecular and ionic components which govern their crystalline packing.
{"title":"Inclusion compounds: structure, kinetics and selectivity","authors":"L. Nassimbeni, Nicole M. Sykes","doi":"10.1080/0889311X.2022.2067849","DOIUrl":"https://doi.org/10.1080/0889311X.2022.2067849","url":null,"abstract":"The physicochemical properties of Inclusion Compounds are described in terms of structure, selectivity, kinetics of decomposition, and enclathration. Their formation and stability are dependent on the phenomenon of molecular recognition. Thus, their thermal behaviour results from the secondary interactions which occur in the various molecular and ionic components which govern their crystalline packing.","PeriodicalId":54385,"journal":{"name":"Crystallography Reviews","volume":"28 1","pages":"70 - 96"},"PeriodicalIF":3.0,"publicationDate":"2022-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45480810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-02DOI: 10.1080/0889311X.2022.2072835
O. Kippes, A. Thorn, G. Santoni
The main focus of drug development against COVID-19 is on the spike protein and proteases. However, such drugs can be problematic because of mutations (in the case of the spike protein) and harmful to cellular homologs (in case of the proteases). Here, we review a viral protein that due to its conserved and multifunctional nature may be an alternative drug target: SARS-CoV-2 nucleocapsid. This protein consists of two ordered and three disordered domains, all of which exhibit RNA binding activity and are important for ribonucleoprotein complex assembly. This complex protects the viral RNA and is important for viral replication. Nucleocapsid might also be connected to modulation of the host cell cycle, replication, translation, viral assembly, and other parts of the infection cycle. The two ordered domains, the RNA binding domain and the dimerization domain, mediate packaging of the RNA into the ribonucleoprotein complex and bind it to membrane proteins. The actual organization of this complex has not been conclusively verified yet, but the large SARS-CoV-2 RNA genome is efficiently packed yet is very flexible. A better understanding of this protein could lead to an efficient therapeutic measure against the virus and would improve our understanding of COVID-19.
{"title":"Structural biology of SARS-CoV-2 nucleocapsid","authors":"O. Kippes, A. Thorn, G. Santoni","doi":"10.1080/0889311X.2022.2072835","DOIUrl":"https://doi.org/10.1080/0889311X.2022.2072835","url":null,"abstract":"The main focus of drug development against COVID-19 is on the spike protein and proteases. However, such drugs can be problematic because of mutations (in the case of the spike protein) and harmful to cellular homologs (in case of the proteases). Here, we review a viral protein that due to its conserved and multifunctional nature may be an alternative drug target: SARS-CoV-2 nucleocapsid. This protein consists of two ordered and three disordered domains, all of which exhibit RNA binding activity and are important for ribonucleoprotein complex assembly. This complex protects the viral RNA and is important for viral replication. Nucleocapsid might also be connected to modulation of the host cell cycle, replication, translation, viral assembly, and other parts of the infection cycle. The two ordered domains, the RNA binding domain and the dimerization domain, mediate packaging of the RNA into the ribonucleoprotein complex and bind it to membrane proteins. The actual organization of this complex has not been conclusively verified yet, but the large SARS-CoV-2 RNA genome is efficiently packed yet is very flexible. A better understanding of this protein could lead to an efficient therapeutic measure against the virus and would improve our understanding of COVID-19.","PeriodicalId":54385,"journal":{"name":"Crystallography Reviews","volume":"28 1","pages":"21 - 38"},"PeriodicalIF":3.0,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44302161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-02DOI: 10.1080/0889311X.2022.2101624
P. Bombicz
The appearance and spread of the virus called Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) has changed our life all around the world. It at least upends people’s lives, but it brings human suffering, what is more it kills people. The COVID-19 pandemic is attacking societies at their core. It has quickly developed into a global health crisis resulted in human, economic and social crises. As a response, the COVID-19 pandemic has increased human solidarity. It includes practical help especially for elderly people and other vulnerable groups but it brought even more in science. The rapid spread of the virus urged quick actions towards new therapeutics, vaccines and medicines. Experiencing the enormous impact of this disease, the researchers have adopted open science methods to fight via global collaborative efforts. The openness leads to research acceleration. Open science consists of open access, open data and open source (availability of research publication, research data and liberal licence terms). SARS-CoV-2 related data are being generated and shared, like virus protein structural results and fragment hits. It took 5 years to develop vaccine after the 2014–2016 Ebola virus epidemic. Vaccine development against SARS-CoV-2 took considerably shorter time, 1.5 years. The COVID related research is an example of global cooperation. Unfortunately, SARS-CoV-2 will likely stay with us as a common pathogen. There is a race against viruses, also newmutations remain a constant thread. It substantiates the necessity of the openness, which hopefully will persist in the future in the discovery of newmedicines and chemicals. The RNA genome of SARS-CoV-2 is one of the largest RNA genomes among RNA viruses. The viral RNA of SARS-CoV-2 encodes many proteins. Accessory and nonstructural proteins facilitate the viral infection cycle after infection. Four types of structural proteins are present in the virion to initiate infection and protect the viral RNA: spike-proteins, envelope-protein, membrane-protein and nucleocapsid. DrAndreaThorn, the head of a research teamat the Institute ofNanostructure and Solid State Physics, University of Hamburg, Germany, has contacted Crystallography Reviews at the end of October 2020 with the idea to publish review articles in a thematic issue on structural biology of the structurally known proteins from SARS-CoV and SARS-CoV-2. Now, there are reviews to fill two special issues with the SARS-CoV related structural biology to improve function–structure relations. She and her collaborators are also publishing a series of blog posts with impressive figures and especially animations. SamHorrell from the Diamond Light Source, Didcot, UK; Gianluca Santoni from European Synchrotron Radiation Facility, Grenoble, France and Andrea Thorn report about the ‘Structural biology of SARS-CoV-2 endoribonuclease NendoU (nsp15)’ in Issue 1 of Volume 28 of Crystallography Reviews. Nsp15 has been one of the lesser explored proteins com
{"title":"COVID – structural research of SARS-CoV-2","authors":"P. Bombicz","doi":"10.1080/0889311X.2022.2101624","DOIUrl":"https://doi.org/10.1080/0889311X.2022.2101624","url":null,"abstract":"The appearance and spread of the virus called Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) has changed our life all around the world. It at least upends people’s lives, but it brings human suffering, what is more it kills people. The COVID-19 pandemic is attacking societies at their core. It has quickly developed into a global health crisis resulted in human, economic and social crises. As a response, the COVID-19 pandemic has increased human solidarity. It includes practical help especially for elderly people and other vulnerable groups but it brought even more in science. The rapid spread of the virus urged quick actions towards new therapeutics, vaccines and medicines. Experiencing the enormous impact of this disease, the researchers have adopted open science methods to fight via global collaborative efforts. The openness leads to research acceleration. Open science consists of open access, open data and open source (availability of research publication, research data and liberal licence terms). SARS-CoV-2 related data are being generated and shared, like virus protein structural results and fragment hits. It took 5 years to develop vaccine after the 2014–2016 Ebola virus epidemic. Vaccine development against SARS-CoV-2 took considerably shorter time, 1.5 years. The COVID related research is an example of global cooperation. Unfortunately, SARS-CoV-2 will likely stay with us as a common pathogen. There is a race against viruses, also newmutations remain a constant thread. It substantiates the necessity of the openness, which hopefully will persist in the future in the discovery of newmedicines and chemicals. The RNA genome of SARS-CoV-2 is one of the largest RNA genomes among RNA viruses. The viral RNA of SARS-CoV-2 encodes many proteins. Accessory and nonstructural proteins facilitate the viral infection cycle after infection. Four types of structural proteins are present in the virion to initiate infection and protect the viral RNA: spike-proteins, envelope-protein, membrane-protein and nucleocapsid. DrAndreaThorn, the head of a research teamat the Institute ofNanostructure and Solid State Physics, University of Hamburg, Germany, has contacted Crystallography Reviews at the end of October 2020 with the idea to publish review articles in a thematic issue on structural biology of the structurally known proteins from SARS-CoV and SARS-CoV-2. Now, there are reviews to fill two special issues with the SARS-CoV related structural biology to improve function–structure relations. She and her collaborators are also publishing a series of blog posts with impressive figures and especially animations. SamHorrell from the Diamond Light Source, Didcot, UK; Gianluca Santoni from European Synchrotron Radiation Facility, Grenoble, France and Andrea Thorn report about the ‘Structural biology of SARS-CoV-2 endoribonuclease NendoU (nsp15)’ in Issue 1 of Volume 28 of Crystallography Reviews. Nsp15 has been one of the lesser explored proteins com","PeriodicalId":54385,"journal":{"name":"Crystallography Reviews","volume":"28 1","pages":"1 - 3"},"PeriodicalIF":3.0,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48967489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-02DOI: 10.1080/0889311X.2022.2098281
Lea C. von Soosten, Maximilian Edich, Kristopher Nolte, J. Kaub, G. Santoni, A. Thorn
With up to 17 domains, non-structural protein 3 (nsp3) is the largest protein of SARS-CoV-2. In part due to its large size, many of its functions still remain a mystery. It is known that nsp3 fulfils several essential functions in the cycle of infection, however most of its domains have not been structurally determined. One of its essential functions is to cleave the polyprotein, which is translated first upon infection, into other functional non-structural proteins. Nsp3 is also involved in the evasion of the host immune system and forms large pore complexes important for viral replication. Furthermore, it interacts with more than 30 other host and viral proteins, resulting in a multitude of potential ways to affect the host cell and viral replication. The many roles of this coronaviral Swiss army knife make it a promising drug target. In this review, we aim to clarify naming conventions and give an overview on the structures and functions of its domains as a starting point for further research.
{"title":"The Swiss army knife of SARS-CoV-2: the structures and functions of NSP3","authors":"Lea C. von Soosten, Maximilian Edich, Kristopher Nolte, J. Kaub, G. Santoni, A. Thorn","doi":"10.1080/0889311X.2022.2098281","DOIUrl":"https://doi.org/10.1080/0889311X.2022.2098281","url":null,"abstract":"With up to 17 domains, non-structural protein 3 (nsp3) is the largest protein of SARS-CoV-2. In part due to its large size, many of its functions still remain a mystery. It is known that nsp3 fulfils several essential functions in the cycle of infection, however most of its domains have not been structurally determined. One of its essential functions is to cleave the polyprotein, which is translated first upon infection, into other functional non-structural proteins. Nsp3 is also involved in the evasion of the host immune system and forms large pore complexes important for viral replication. Furthermore, it interacts with more than 30 other host and viral proteins, resulting in a multitude of potential ways to affect the host cell and viral replication. The many roles of this coronaviral Swiss army knife make it a promising drug target. In this review, we aim to clarify naming conventions and give an overview on the structures and functions of its domains as a starting point for further research.","PeriodicalId":54385,"journal":{"name":"Crystallography Reviews","volume":"28 1","pages":"39 - 61"},"PeriodicalIF":3.0,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42822806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-02DOI: 10.1080/0889311X.2022.2035374
M. Loubser
This E-book is a collection of articles on the application of portable X-ray fluorescence (PXRF) spectrometry and portable X-ray powder diffractometry (PXRD) for geochemistry applications, particularly in soils and sediments.
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Pub Date : 2022-01-02DOI: 10.1080/0889311X.2022.2065270
S. Horrell, G. Santoni, A. Thorn
The SARS-CoV-2’s endoribonuclease (NendoU) nsp15, is an Mn2+ dependent endoribonuclease specific to uridylate that SARS-CoV-2 uses to avoid the innate immune response by managing the stray RNA generated during replication. As of the writing of this review 20 structures of SARS-CoV-2 nsp15 have been deposited into the PDB, largely solved using X-ray crystallography and some through Cryo-EM. These structures show that an nsp15 monomer consist of three conserved domains, the N-terminal oligomerization domain, the middle domain, and the catalytic NendoU domain. Enzymatically active nsp15 forms a hexamer through a dimer of trimers (point group 32), whose assembly is facilitated by the oligomerization domain. This review summarises the structural and functional information gained from SARs-CoV-2, SARs-CoV and MERS-CoV nsp15 structures, compiles the current structure-based drug design efforts, and complementary knowledge with a view to provide a clear starting point for downstream structure users interested in studying nsp15 as a novel drug target to treat COVID-19.
{"title":"Structural biology of SARS-CoV-2 endoribonuclease NendoU (nsp15)","authors":"S. Horrell, G. Santoni, A. Thorn","doi":"10.1080/0889311X.2022.2065270","DOIUrl":"https://doi.org/10.1080/0889311X.2022.2065270","url":null,"abstract":"The SARS-CoV-2’s endoribonuclease (NendoU) nsp15, is an Mn2+ dependent endoribonuclease specific to uridylate that SARS-CoV-2 uses to avoid the innate immune response by managing the stray RNA generated during replication. As of the writing of this review 20 structures of SARS-CoV-2 nsp15 have been deposited into the PDB, largely solved using X-ray crystallography and some through Cryo-EM. These structures show that an nsp15 monomer consist of three conserved domains, the N-terminal oligomerization domain, the middle domain, and the catalytic NendoU domain. Enzymatically active nsp15 forms a hexamer through a dimer of trimers (point group 32), whose assembly is facilitated by the oligomerization domain. This review summarises the structural and functional information gained from SARs-CoV-2, SARs-CoV and MERS-CoV nsp15 structures, compiles the current structure-based drug design efforts, and complementary knowledge with a view to provide a clear starting point for downstream structure users interested in studying nsp15 as a novel drug target to treat COVID-19.","PeriodicalId":54385,"journal":{"name":"Crystallography Reviews","volume":"28 1","pages":"4 - 20"},"PeriodicalIF":3.0,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48334010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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