scholarly journals Foundational research and NIH funding enabling Emergency Use Authorization of remdesivir for COVID-19

2020 ◽  
Author(s):  
Ekaterina Galkina Cleary ◽  
Matthew J. Jackson ◽  
Zoe Folchman-Wagner ◽  
Fred D. Ledley
Keyword(s):  
Public Sector ◽  
Chemical Structure ◽  
Nucleoside Analogs ◽  
Basic Research ◽  
The Body ◽  
New Drugs ◽  
Biological Target ◽  
Foundational Research ◽  
Nih Funding ◽  
Targeted Drug Discovery

Emergency Use Authorization for remdesivir months after discovery of COVID19 is unprecedented. Typically, decades of research and public sector funding are required to establish the mature body of foundational research requisite for efficient, targeted drug discovery and development. This work quantifies the body of research related to the biological target of remdesivir, RNA-dependent RNA polymerase (RdRp), or parent chemical structure, nucleoside analogs (NcAn), through 2019, as well as NIH funding for this research from 2000 to 2019. There were 6,567 RdRp related publications in PubMed, including 1,263 with NIH support, and 11,073 NcAn-related publications, including 2,319 with NIH support. NIH support for RdRp research comprised 2,203 Project Years with Costs of $1,875 million. NIH support for NcAn research comprised 4,607 Project Years with Costs of $4,612 million. Research Project grants accounted for 63% and 48% of Project Years for RdRp and NcAn respectively, but only 19% and 12% of Project Costs. Analytical modeling of research maturation estimates that RdRp and NcAn research passed an established maturity threshold in 2008 and 1994 respectively. Of 97 investigational compounds targeting RdRp since 1989, the three authorized for use entered clinical trials after both thresholds. This work demonstrates the scale of foundational research on the biological target and parent chemical structure of remdesivir that supported its discovery and development for COVID19. This work identifies $6.5 billion in NIH funding for research leading to remdesivir, underscoring the role of public sector investments in basic research and research infrastructure that underlie new drugs and the response to emergent disease.

scholarly journals Government as the First Investor in Biopharmaceutical Innovation: Evidence From New Drug Approvals 2010–2019

2020 ◽  
pp. 1-72
Author(s):  
Ekaterina Galkina Cleary ◽  
Matthew J. Jackson ◽  
Fred D. Ledley
Keyword(s):  
Public Sector ◽  
Public Investment ◽  
Basic Research ◽  
Linear Process ◽  
New Drugs ◽  
Biomedical Science ◽  
Biological Targets ◽  
Working Paper ◽  
New Drug ◽  
Nih Funding

The discovery and development of new medicines classically involves a linear process of basic biomedical research to uncover potential targets for drug action, followed by applied, or translational, research to identify candidate products and establish their effectiveness and safety. This Working Paper describes the public sector contribution to that process by tracing funding from the National Institutes of Health (NIH) related to published research on each of the 356 new drugs approved by the U.S. Food and Drug Administration from 2010-2019 as well as research on their 219 biological targets. Specifically, we describe the timelines of clinical development for these products and proxy measures of their importance, including designations as first-in- class or expedited approvals. We model the maturation of basic research on the biological targets to determine the initiation and established points of this research and demonstrate that none of these products were approved before this enabling research passed the established point. This body of essential research comprised 2 million publications, of which 424 thousand were supported by 515 thousand Funding Years of NIH Project support totaling $195 billion. Research on the 356 drugs comprised 244 thousand publications, of which 39 thousand were supported by 64 thousand Funding Years of NIH Project support totaling $36 billion. Overall, NIH funding contributed to research associated with every new drug approved from 2010-2019, totaling $230 billion. This funding supported investigator-initiated Research Projects, Cooperative Agreements for government-led research on topics of particular importance, as well as Research Program Projects and Centers and training to support the research infrastructure. This NIH funding also produced 22 thousand patents, which provided marketing exclusivity for 27 (8.6%) of the drugs approved 2010-2019. These data demonstrate the essential role of public sector-funded basic research in drug discovery and development, as well as the scale and character of this funding. It also demonstrates the limited mechanisms available for recognizing the value created by these early investments and ensuring appropriate public returns. This analysis demonstrates the importance of sustained public investment in basic biomedical science as well as the need for policy innovations that fully realize the value of public sector investments in pharmaceutical innovation that ensure that these investments yield meaningful improvements in health.

scholarly journals 2017 FDA Peptide Harvest

2018 ◽  
Author(s):  
Othman Al Musaimi ◽  
Danah Alshaer ◽  
Beatriz G. de la Torre ◽  
Fernando Albericio
Keyword(s):  
Mode Of Action ◽  
Chemical Structure ◽  
New Drugs ◽  
Synthetic Strategy ◽  
Biological Target

2017 was an excellent year in terms of new drugs (chemical entities and biologics) approved by the FDA, with a total of forty-six. In turn, one of the highlights was the number of peptides (six) included in this list. Here, the six peptides are analysed in terms of chemical structure, synthetic strategy used for their production, source, biological target, and mode of action.

A multi-method and structure-based in silico vaccine designing against Helicobacter pylori employing immuno-informatics approach

2020 ◽  
Vol 17 ◽  
Author(s):  
Anam Naz ◽  
Tahreem Zaheer ◽  
Hamza Arshad Dar ◽  
Faryal Mehwish Awan ◽  
Ayesha Obaid ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Vaccine Development ◽  
Amino Acid Sequences ◽  
The Body ◽  
New Drugs ◽  
Toll Like Receptor ◽  
Peptide Vaccines ◽  
Hla Alleles ◽  
Vaccine Candidates ◽  
H Pylori

Background: Helicobacter pylori infection and its treatment still remains a challenge to human health worldwide. A variety of antibiotics and combination therapies are currently used to treat H. pylori induced ulcers and carcinoma; however, no effective treatment is available to eliminate the pathogen from the body. Additionally, antibiotic resistance is also one of the main reasons for prolonged and persistent infection. Aim of the study: Until new drugs are available for this infection, vaccinology seems the only alternative opportunity to exploit against H. pylori induced diseases. Methods: Multiple epitopes prioritized in our previous study have been tested for their possible antigenic combinations, and results in 169-mer and 183-mer peptide vaccines containing the amino acid sequences of 3 and 4 epitopes respectively, along with adjuvant (Cholera Toxin Subunit B adjuvant at 5’ end) and linkers (GPGPG and EAAAK). Results: Poly-epitope proteins proposed as potential vaccine candidates against H. pylori include SabAHP0289-Omp16-VacA (SHOV), VacA-Omp16-HP0289-FecA (VOHF), VacA-Omp16-HP0289-SabA (VOHS), VacA-Omp16-HP0289-BabA (VOHB), VacA-Omp16-HP0289-SabA-FecA (VOHSF), VacAOmp16-HP0289-SabA-BabA (VOHSB) and VacA-Omp16-HP0289-BabA-SabA (VOHBS). Structures of these poly-epitope peptide vaccines have been modelled and checked for their affinity with HLA alleles and receptors. These proposed poly-epitope vaccine candidates bind efficiently with A2, A3, B7 and DR1 superfamilies of HLA alleles. They can also form stable and significant interactions with Toll-like receptor 2 and Toll-like receptor 4. Conclusion: Results suggest that these multi-epitopic vaccines can elicit a significant immune response against H. pylori and can be tested further for efficient vaccine development.

Detection of psychotropic substances in the blood by LC/MS/MS

2014 ◽  
Vol 284 ◽  
pp. 60-69
Author(s):  
Mariola Wicka ◽  
◽  
Piotr Chołbiński ◽  
Dorota Kwiatkowska ◽  
Andrzej Pokrywka ◽  
...  
Keyword(s):  
Human Body ◽  
Chemical Structure ◽  
Drugs Of Abuse ◽  
Point Of View ◽  
The Body ◽  
Psychoactive Substances ◽  
Psychotropic Substances ◽  
Road Users ◽  
Conducting Research ◽  
Proper Interpretation

Year on year, one can observe an increase in the use of addictive substances. This leads to occurring the problem of addiction as well as the use of psychoactive substances as a serious hazard to road users. The Regulation of the Minister of Health on agents acting similarly to alcohol and the conditions and manner of conducting research on their presence in the human body, requires adequate benchmarks for performing these tests. An importantfactor, from consultative point of view, is the knowledge of the chemical structure of substances belonging to different groups of drugs of abuse, their metabolic transformations that occur in the body as well as their influence on the body. This is to aid in the proper interpretation of the results of the analytical tests.

MICROSCOPIC CHANGES IN THE INTERNAL ORGANS OF WHITE MICE DURING EXPERIMENTAL IRON (IV) CLATHROCHELATE TOXICOSIS

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
B. V. Borysevych ◽  
◽  
V. V. Lisova ◽  
I. M. Derkach ◽  
S. S. Derkach ◽  
...  
Keyword(s):  
Biological Response ◽  
Organ Damage ◽  
The Body ◽  
New Drugs ◽  
Laboratory Animals ◽  
Internal Organs ◽  
Experimental Drug ◽  
Liver And Kidney ◽  
Preclinical And Clinical Studies ◽  
First Time

Iron (IV) clathrochelate based on a macrobicyclic ligand of the hexahydrazide type is a unique compound that contains iron in a rare high valence IV. Preclinical and clinical studies of this complex, which were started for the first time in Ukraine, have an important theoretical and practical consequence as this complex can be recommended as an active substance in iron-containing drugs with antianemic action. In conducting preclinical studies of new drugs, pathomorphological studies are important because they are a necessary step in studying the biological response of animals to the action of test substances. It was found that some pathological changes develop in the body of white mice under conditions of experimental acute and chronic iron (IV) clathrochelate intoxication. They correlated with the dose of the test compound. During chronic intoxication, the microscopic changes in the liver and kidney of white mice treated with iron (IV) clathrochelate at a dose of 1/10 DL50 were similar to the microscopic changes in the liver and kidney of mice treated with the experimental drug at a dose of 1/5 DL50. However, the severity of these changes was lower, reflecting a lower degree of organ damage. In the myocardium of mice treated with iron (IV) clathrochelate at a dose of 1/5 DL50 on the 10th day, as in acute iron (IV) clathrochelate poisoning, only edema was recorded. The prospects for further research are the study of microscopic changes in the organs of laboratory animals of other species during experimental iron (IV) clathrochelate toxicosis.

scholarly journals Experiencing Event Management During the Coronavirus Pandemic: A Public Sector Perspective

2022 ◽  
Vol 3 ◽  
Author(s):  
Tim Coles ◽  
Giselle Garcia ◽  
Evelyn O'Malley ◽  
Cathy Turner
Keyword(s):  
Public Sector ◽  
Local Authority ◽  
The Body ◽  
Event Management ◽  
Local Authorities ◽  
Key Stakeholders ◽  
The World ◽  
Local Recovery ◽  
The Uk ◽  
Opening Up

Events have played a significant role in the way in which the Coronavirus pandemic has been experienced and known around the world. Little is known though about how the pandemic has impacted on supporting, managing and governing events in municipal (i.e., local) authorities as key stakeholders, nor how events have featured in the opening-up of localities. This paper reports on empirical research with senior events officers for local authorities in the UK on these key knowledge gaps. Specifically, it examines events officers' unfolding experiences of the pandemic. The paper points to unpreparedness for a crisis of this scale and magnitude, and the roles of innovation, adaptation and co-production in the emergent response. It highlights the transformative nature of the pandemic through reconsiderations of the purpose of public sector involvement in events and, from a policy perspective, how relatively smaller-scale, more agile and lower-risk arts events and performances can figure in local recovery. Finally, while the effects on, and response of, the body corporate (the local authority) to crises is an obvious focus, it is important to recognise those of the individuals who manage the response and drive change.

scholarly journals THE USE OF BIOSTIMULANT FOR INCREASING THE BODY WEIGHT GAIN OF CHICKENS

2020 ◽  
Vol 17 (35) ◽  
pp. 800-812
Author(s):  
Ilgiz DOLININ ◽  
George BAZEKIN ◽  
Evgeny SKOVORODIN ◽  
Almaz SHARIPOV ◽  
Ivan CHUDOV
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Broiler Chickens ◽  
Body Weight Gain ◽  
Live Weight ◽  
The Body ◽  
New Drugs ◽  
Natural Resistance ◽  
Control Group ◽  
Immunological Parameters

Poultry farming holds a special place in ensuring the products that the consumers demand, it provides the population with essential food products,such as eggs and meat,that contain vital micro and macronutrients, proteins, lipids, and vitamins. Therefore, the issues of rational, economically feasible feeding of meat poultry, namely broiler chickens, are an urgent task. It is also essential to find effective methods of their application in order to correct the natural resistance and immune and biological reactivity of birds. The purpose of this research is to study the effect of the biological stimulant-Nucleostim on the growth and development of chickens, hematological, and immunological parameters of the blood of birds.This Biostimulant is a purified bovine spleen extract containing at least 1 mg / ml of low molecular weight peptides (nucleotides and nucleosides) formed as a result of autolysis, using dry whey and diatomite as fillers. Onthe application ofNucleostim, the gain in live weight of chickens was increased by 9.7%. At the end of the experiment, the livability of the chicks of the experimental group treated with Nucleostimcame up to 88%, compared with the 72% of the control group. The use of biostimulant had a stimulating effect on the liver of chickens confirmed by the research results presented in the article, as well as contributed to the development of the thymus in the setting of general dystrophy. Thus, it improved chicklivability and increased body weight gain. The biological stimulant-Nucleostim as an adaptogenic, anabolic, and immunostimulatory agent is promising for finding new drugs that improve the health and productivity of poultry.

scholarly journals Epac signaling protein ligands as tools for studying their biological activity and creating new original drugs

2020 ◽  
pp. 3-17
Author(s):  
G. V. Mokrov ◽  
T. D. Nikiforova ◽  
S. A. Kryzhanovskiy
Keyword(s):  
Biological Activity ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
The Body ◽  
Physiological Functions ◽  
Signaling Protein ◽  
Protein Ligands ◽  
Biological Target ◽  
Effective Drugs ◽  
Structure And Functions

The review discusses modern views about the structure and functions of Epac proteins (exchange proteins directly activated by cyclic adenosine monophosphate). The involvement of Epac proteins both in the regulation of the physiological functions of the body and in the initiation of various pathological processes allows to consider them as a fundamentally new biological target for creating original, highly effective drugs. Information on existing Epac protein agonists and antagonists was collected, and the influence of Epac ligands structure on the values of their affinity and selectivity was analyzed. Presumptive mechanisms of the interaction of ligands with Epac proteins are presented.

scholarly journals A Preliminary Up-To-Date Review on Pakistani Medicinal Plants with Potential Antioxidant Activity

2020 ◽  
Vol 11 (1) ◽  
pp. 1-27
Author(s):  
Adil Hussain
Keyword(s):  
Antioxidant Activity ◽  
Free Radicals ◽  
Medicinal Plants ◽  
Natural Antioxidants ◽  
The Body ◽  
New Drugs ◽  
Lung Damage ◽  
Present Review ◽  
Experimental Investigations ◽  
Health Related

Background: There exist natural antioxidants in plants that scavenge harmful free radicals from the body. Free radicals are species of chemical origin with an unpaired electron and play a pivotal role in combating against health-related problems like lung damage, inflammation, and cardiovascular ailments etc. Antioxidants halt the development of these free radicals called the reactive oxygen species either by chelating the trace elements or by enzymes inhibition. Objectives: The aim of present review was to collect information about Pakistani medicinally important plants with the exploration of their antioxidant potential. Methodology: Total 206 papers were looked over, which were obtained from numerous sources like; Google Scholar, Medline, PubMed, Research Gate, Science Direct, Scopus and Web of Science. Results: Overall, 93 plants representing 44 families with potential antioxidant activity reported from Pakistan have been presented in this review. Maximum number of species from Asteracea, Poaceae and Rutaceae familes were scrutinized for their potential antioxidant activity from Pakistan. Conclusion: The present review clearly designates that the presence of phytochemicals and antioxidant activity of medicinal plants from Pakistan vary with the species of the plants and material/extracts used. From this review, it is recommended to perform comprehensive experimental investigations based on toxicology and ethnopharmacology on these precious plants from Pakistan. It will be advantageous in the provision of trustworthy information to patients and determine further innovative compounds for safer and new drugs development with fewer side effects.

scholarly journals Trypanosoma cruzi Presenilin-Like Transmembrane Aspartyl Protease: Characterization and Cellular Localization

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1564
Author(s):  
Guilherme C. Lechuga ◽  
Paloma Napoleão-Pêgo ◽  
Carolina C. G. Bottino ◽  
Rosa T. Pinho ◽  
David W. Provance-Jr ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Cellular Localization ◽  
Secretory Pathway ◽  
Chronic Phase ◽  
Basic Research ◽  
New Drugs ◽  
Public Health Issue ◽  
Spot Synthesis ◽  
Major Public Health Issue ◽  
Computational Analyses

The increasing detection of infections of Trypanosoma cruzi, the etiological agent of Chagas disease, in non-endemic regions beyond Latin America has risen to be a major public health issue. With an impact in the millions of people, current treatments rely on antiquated drugs that produce severe side effects and are considered nearly ineffective for the chronic phase. The minimal progress in the development of new drugs highlights the need for advances in basic research on crucial biochemical pathways in T. cruzi to identify new targets. Here, we report on the T. cruzi presenilin-like transmembrane aspartyl enzyme, a protease of the aspartic class in a unique phylogenetic subgroup with T. vivax separate from protozoans. Computational analyses suggest it contains nine transmembrane domains and an active site with the characteristic PALP motif of the A22 family. Multiple linear B-cell epitopes were identified by SPOT-synthesis analysis with Chagasic patient sera. Two were chosen to generate rabbit antisera, whose signal was primarily localized to the flagellar pocket, intracellular vesicles, and endoplasmic reticulum in parasites by whole-cell immunofluorescence. The results suggest that the parasitic presenilin-like enzyme could have a role in the secretory pathway and serve as a target for the generation of new therapeutics specific to the T. cruzi.

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