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Cell culture studies in Frankfurt and Canterbury previously showed effects of Aprotinin against SARS-CoV-2
A clinical study from Spain recently confirmed laboratory experiments made by researchers of Goethe University Frankfurt and University of Kent who showed that the protease inhibitor aprotinin prevented cells to be infected by SARS-CoV2. The authors of the clinical study report that patients receiving an aprotinin aerosol could be discharged from hospital significantly earlier.
FRANKFURT. SARS-CoV-2, the coronavirus that causes
COVID-19, needs its spike proteins to dock onto proteins (ACE receptors) on the
surface of the host cells. Before this docking is possible, parts of the spike
protein have to be cleaved by host cell's enzymes called proteases. In 2020, a
scientific team led by Professor Jindrich Cinatl (Goethe University Frankfurt,
Germany), Professor Martin Michaelis and Professor Mark Wass (both University
of Kent, UK), conducted cell culture experiments and found that aprotinin, a
protease inhibitor, could inhibit virus replications by preventing SARS-CoV-2
entry into host cells.
In a more recent study, the research
consortium further showed that aprotinin is also effective against the Delta
and Omicron variants.
Now, a Spanish research consortium has
published the findings of a phase III clinical study investigating the use of
an aprotinin aerosol in COVID-19 patients. Among other improvements, aprotinin
treatment reduced the length of hospital stays by five days.
Professor Jindrich Cinatl, Goethe
University Frankfurt, said: “This shows how scientific collaborations work even
without a direct relationship between researchers. I am very glad that our cell
culture study inspired this successful clinical trial".
Professor Martin Michaelis, University of
Kent, said: “Our cell culture data looked very convincing. It is exciting that
aprotinin has now also been shown to be effective against COVID-19 in
patients."
Spanish
study: Francisco Javier Redondo-Calvo et. al.:
Aprotinin treatment against SARS-CoV-2: A randomized phase III study to
evaluate the safety and efficacy of a pan-protease inhibitor for moderate
COVID-19. Eur. J. Clin. Invest. (2022) https://doi.org/10.1111/eci.13776
More
about the studies of Goethe University and University of Kent:
1) The drug aprotinin inhibits entry of
SARS-CoV2 in host cells https://aktuelles.uni-frankfurt.de/englisch/the-drug-aprotinin-inhibits-entry-of-sars-cov2-in-host-cells/
2) Researchers of the University of Kent
and Goethe-University find explanation why the Omicron variant causes less
severe disease https://aktuelles.uni-frankfurt.de/englisch/researchers-of-the-university-of-kent-and-goethe-university-find-explanation-why-the-omicron-variant-causes-less-severe-disease/
Further
Information:
Professor Jindrich
Cinatl
Institute of Medical Virology
University Hospital Frankfurt and Goethe University Frankfurt
Phone.: +49 (0) 69 6301-6409
cinatl@em.uni-frankfurt.de
Online program promotes exercise and maintains well-being during pandemic
Interactive training programs for use at home can make the restrictions during a lockdown more bearable. The live-streaming of sports offerings allows for a significant increase in physical activity, revealed a research team from ten countries headed by the Institute of Sport Science at Goethe University Frankfurt. At the same time well-being improved compared to an inactive control group. One year previously, the team had described the negative impacts of coronavirus restrictions on exercise and well-being.
FRANKFURT. People
were about 40 per cent less active during the first lockdown in the spring of 2020.
This has been revealed by an international study headed by Goethe University
Frankfurt. Psychological well-being also declined, with the proportion of
people at risk of depression increasing threefold. In order to cushion the
effects of this negative development, the research team designed an online training
program for use at home and studied whether the physical activity that is so
important to general health could be maintained during a lockdown. The results
of the study were recently published in the British Journal of Sports Medicine.
Of 763 healthy subjects from nine
countries on four continents, half trained for four weeks using a live-stream program,
the others formed the control group. Those training could select from a number
of daily workouts – for example with the focus on strength, endurance, balance
or relaxation. Professional trainers actively accompanied them with a camera
and microphone. Each week both groups completed standardised questionnaires on physical activity, anxiety, mental well-being, quality
of sleep, pain and sport motivation.
The training program was particularly
effective in improving movement behavior in the participants: physical activity
was initially as much as 65 per cent higher on average in the online group than
in the comparison group, and still 20 to 25 per cent higher after four weeks. Thus,
the course participants clearly surpassed the WHO recommendations of at least 150
minutes of moderate or 75 minutes of intensive exercise per week, while the control
group only just attained these. At the same time the motivation to do sport,
psychological well-being and sleep improved, and anxiety levels decreased.
“While these improvements are minor, they are nevertheless potentially relevant,"
stresses study head Dr. Jan Wilke from the Institute
of Sport Science at Goethe University Frankfurt. “Our participants were all
healthy – the effects with patients could be significantly greater, in
particular with people who have chronic disease." In addition, he said, four
weeks is a very short period for such efficacy studies. Participants who took
part in at least two courses per week stated their fitness was even better and they
had a greater feeling of well-being, yet did not note any further improvement
with sleep or fears.
Unfortunately, only just under half of the
participants completed the study. The research group attributed this in
particular to the considerable effort of completing the questionnaires each week.
This frequent information retrieval was intended to ensure that the study would
allow conclusions to be drawn even if the lockdown regulations were relaxed. The
changes in local conditions in the same period could also have lowered the motivation
of some participants, for example if local fitness studios had reopened.
Moreover, the requirements were very strict: those who did not respond by
completing the questionnaire were eliminated from the study.
“Train at home, but not alone" – it is
best to train at home with others, this is how the working group summarised its
findings on exercise offerings in the pandemic-induced lockdown. For: following
the main section of the study – the live-streaming – when both groups had
access to recorded contents, the differences that had been observed declined in
part. According to Wilke, this is due to both the activation of the control group
as well as to the change in the form of the physical activity intervention
(live vs. recorded).
The study authors expressly underline the importance
of exercise in our daily lives: in line with the latest data, physical inactivity
causes eight to nine per cent of all premature deaths, increases the risk of
cardiac disease, metabolic disorders and cancers, as well as proneness to the
novel coronavirus. They believe that it is probably all the more important in
lockdown to offer online training for people with chronic illnesses – for
example diabetics – whose health could possibly suffer additionally under the
restrictions imposed by a pandemic.
Publication:
Jan Wilke, Lisa Mohr, Gustavo Yuki, Adelle
Kemlall Bhundoo, David Jiménez-Pavón, Fernando Laiño, Niamh Murphy, Bernhard
Novak, Stefano Nuccio, Sonia Ortega-Gómez, Julian David Pillay, Falk Richter,
Lorenzo Rum, Celso Sanchez-Ramírez, David Url, Lutz Vogt, Luiz Hespanhol. Train at home, but not alone: a randomised
controlled multicentre trial assessing the effects of live-streamed
tele-exercise during COVID-19-related lockdowns. Br. J. Sports Med. (2022) https://doi.org/10.1136/bjsports-2021-104994
Picture
download:
https://www.uni-frankfurt.de/117155105
Caption:
Sports offerings via live streaming promotes
activity and well-being during pandemic lockdowns. Photo: Jan Wilke,
Goethe-University Frankfurt
Further
information:
Dr. phil. Jan Wilke
Institute of Sports Sciences
Goethe University Frankfurt, Germany
Phone +49 (69) 798-24588,
wilke@sport.uni-frankfurt.de
Structure of key enzyme unravelled – possible starting point for antibacterial agents
A team from Research Unit 2251 of the German Research Foundation led by Goethe University has shed light on the structure of an enzyme important in the metabolism of the pathogenic bacterium Acinetobacter baumannii. The enzyme “MtlD" is critical for the bacterium's synthesis of the sugar alcohol mannitol, with which it protects itself against water loss and desiccation in dry or salty environments such as blood or urine. Structural analysis has revealed weak spots where it might be possible to inhibit the enzyme and thus attack the pathogen. (PNAS, DOI: 10.1073/pnas.2107994119)
FRANKFURT. Each
year, over 670,000 people in Europe fall ill through pathogenic bacteria that
are resistant to antibiotics, and 33,000 die of the diseases they cause. In
2017, the WHO named antibiotic resistance as one of the greatest threats to
health worldwide. Especially feared are pathogens that are resistant to several
antibiotics. Among them, Acinetobacter
baumannii stands out, a bacterium with an extraordinarily pronounced
ability to develop multiresistance and, as a “hospital superbug", dangerous
above all for immunosuppressed patients. Acinetobacter
baumannii is highly resilient because it can remain infectious for a long
time even in a dry environment and thus endure on the keyboards of medical
devices or on ward telephones and lamps. This property also helps the microbe
to survive on dry human skin or in body fluids such as blood and urine, which
contain relatively high concentrations of salts and other solutes.
The team from
Research Unit 2251 of the German Research Foundation led by Goethe University
has now shed light on a central mechanism via which Acinetobacter
baumannii settles in
such an adverse environment: like many bacteria as well as plants or fungi, Acinetobacter
baumannii is able to synthesize the sugar alcohol mannitol,
a substance excellent at binding water. In this way, Acinetobacter baumannii prevents desiccation.
Almost unique, however, is the way that Acinetobacter baumannii synthesizes mannitol:
instead of two enzyme complexes as are common in most organisms, the two last
steps in mannitol synthesis are catalysed by just one. A team of researchers
led by Professor Beate Averhoff and Professor Volker Müller already discovered
this “MtlD" enzyme with two catalytic activities back in 2018. The team headed
by Professor Klaas Martinus Pos, who is also a member of the Research Unit, has
now succeeded in shedding light on the enzyme's spatial structure.
He explains: “We've discovered that the
enzyme is usually present in the form of free monomers. Although these have the
necessary catalytic activities, they are inactive. Only a dry or salty
environment triggers what is known as 'osmotic stress' in the bacterium, after
which the monomers aggregate as dimers. Only then does the enzyme become active
and synthesize mannitol." The researchers have also identified which parts in
the structure are particularly important for the enzyme's catalytic functions
and for dimer formation.
Professor Volker Müller, spokesperson for
Research Unit 2251, is convinced: “Our work constitutes an important new
approach for fighting this hospital pathogen since we've identified a
biochemically sensitive point in the pathogen's metabolism. In the future, this
could be the starting point for customized substances to inhibit the enzyme."
Publication:
Heng-Keat Tam, Patricia König, Stephanie
Himpich, Ngoc Dinh Ngu, Rupert Abele, Volker Müller, Klaas M. Pos: Unidirectional mannitol synthesis of
Acinetobacter baumannii MtlD is facilitated by the helix-loop-helix-mediated
dimer formation. Proc. Natl. Acad. Sci. U.S.A. (2022) https://www.pnas.org/doi/full/10.1073/pnas.2107994119
Picture
download:
1) Mannitol-Synthesizing
Enzyme
https://www.uni-frankfurt.de/116943466
Caption:
Resembles a butterfly: only in its dimer
form does the mannitol-synthesizing enzyme of the hospital pathogen Acinetobacter baumannii protect the
bacterium from water loss and desiccation. Picture: Klaas Martinus Pos, Goethe University
Frankfurt
2) Acinetobacter baumannii
https://commons.wikimedia.org/wiki/File:Acinetobacter_baumannii.JPGCaption: Scanning electron micrograph (SEM) of a highly magnified cluster of
Gram-negative, non-motile Acinetobacter
baumannii bacteria. Photo: Janice Carr
Further
information:
Professor Volker Müller
Research Unit 2251 Spokesperson
Department of Molecular Microbiology & Bioenergetics
Institute for Molecular Biosciences
Goethe University Frankfurt, Germany
Tel.:
+49 (0)69 798-29507
vmueller@bio.uni-frankfurt.de
Professor Klaas Martinus Pos
Membrane Transport Machineries Group
Institute of Biochemistry
Goethe University Frankfurt, Germany
Tel.: +49 (0)69 798-29251
pos@em.uni-frankfurt.de
Fundamental research for novel approaches for the control of Trypanosoma parasites
In Central and South America, predatory blood-sucking bugs transmit the causative agent of the widely prevalent Chagas disease. As the disease can induce severe symptoms and to date there is no vaccine against the Trypanosoma parasites, the main approach at present is to control the bug using insecticides. A German-Brazilian research team has now studied how trypanosomes change the bug's intestinal microbiota. The long-term goal: to change the bacterial community in the predatory bug's intestine in such a way that it can defend itself against the trypanosomes.
FRANKFURT. According
to estimates by the World Health Organization (WHO), between six and seven
million people worldwide, predominantly in Central and South America, are
infected with the Trypanosoma cruzi species
of trypanosome. This
single-celled (protozoan) parasite causes Chagas disease (American trypanosomiasis),
which in the acute phase is inconspicuous: only in every third case does the infected
person develop any symptoms at all, which can then be unspecific, such as
fever, hives and swollen lymph nodes. However, the parasites remain in the body,
and many years later chronic Chagas disease can become life-threatening, with pathological
enlargement of the heart and progressive paralysis of the gastrointestinal
tract.
There is no vaccine against the pathogen
and treating the disease in the advanced stage is difficult. That is why the
focus in Latin America is rather on controlling the bug that transmits Chagas
trypanosomes: the predatory blood-sucking bug of the insect subfamily Triatominae. It ingests the trypanosomes
during the sting, which then colonize its intestine. Through its faeces that it
mostly deposited next to the bite, the bug excretes the pathogen, which is
often rubbed into the wound when scratching the extremely itchy bite.
Although the number of new infections has
dropped in various regions where insecticides are sprayed on a wide scale,
problems are emerging: over the last decade, resistance to common insecticides
by several species of predatory bugs has been increasingly observed. These
insecticides also have a negative impact on the environment and the local population.
Researchers worldwide are making intense
efforts to find alternative methods to help control Trypanosoma cruzi. One possibility might be to modify bacteria in
the predatory bug's intestine in such a way that they eliminate the Chagas trypanosomes
or inhibit their development.
In collaboration with scientists at the
Instituto René Rachou in Belo Horizonte, Brazil, parasitologists and infection
biologists Fanny Eberhard and Professor Sven Klimpel from Goethe University, the
Senckenberg – Leibniz Institution for Biodiversity and Earth System Research
(SGN) and the LOEWE Centre for Translational Biodiversity Genomics have now investigated
how Chagas trypanosomes change the bacterial community in the predatory bug's
intestine. To do so, they used genome analysis, which allowed them to compare
the composition of the bacterial community in the bug's intestine, the
microbiome, before and after infection with the pathogen (metagenomic shotgun sequencing).
The result: after the infection, the range
of bacterial strains in the bug's intestine significantly decreased. Certain
strains, including the potentially pathogenic bacterium Enterococcus faecalis, profited from the parasites' presence.
Moreover, the researchers succeeded in identifying four bacterial species that
probably take on functions important for the bug, such as the synthesis of B
vitamins.
Fanny Eberhard explains: “Vitamin B is one
of the nutrients that blood-sucking insects do not obtain through their blood
meals. Bacteria that produce vitamin B are therefore very important for the
bug, are found in practically all individuals and stay in the predatory bug's
intestine even across generations. Hence, such bacteria are potentially
suitable recipients for genes that produce defensive substances against Chagas
trypanosomes."
Professor Sven Klimpel elaborates: “Ultimately,
our goal is for the predatory bug to defend itself against Chagas trypanosomes and,
in this way, to prevent infection in humans. However, before we can produce
bacteria with such properties and then release predatory bugs containing them,
we need to understand better how the ecology of the bug's intestine is
structured and how the extensive interactions between host, pathogen and microbiome
function. Our work is delivering an essential contribution to this."
Publication:
Fanny E. Eberhard, Sven Klimpel,
Alessandra A. Guarneri, Nicholas J. Tobias. Exposure to Trypanosoma parasites induces changes in the microbiome of the
Chagas disease vector Rhodnius prolixus.
Microbiome (2022) 10:45. https://doi.org/10.1186/s40168-022-01240-z
Picture
download: https://www.uni-frankfurt.de/116081371
Captions:
Rhodnius prolixus_1000px.jpg
The predatory bug Rhodnius prolixus is one of the main vectors of Chagas disease in
the north of South America and in Central America. Photo: Dr Erwin Huebner,
University of Manitoba, Winnipeg, Canada/ Wikimedia Commons
Rhodnius prolixus_Life_cycle.jpg
Example of the hemimetabolic life cycle of the predatory
triatomine bug Rhodnius prolixus. Shown
are the adult vector, freshly laid, milky-white eggs, mature, reddish eggs and
five nymphs. Red arrows mark a blood meal for the moulting process and egg
production. Pictured in the middle are frequent hosts, such as dogs, opossums
and humans. Graphics: Fanny E. Eberhard
Further
information:
Professor Sven Klimpel
Institute of Ecology, Diversity and Evolution, Goethe University
Senckenberg – Leibniz Institution for Biodiversity and Earth System Research
(SGN)
LOEWE Centre for Translational
Biodiversity Genomics
Tel. +49 (0)69 798-42249
Klimpel@bio.uni-frankfurt.de
https://www.bio.uni-frankfurt.de/43925886/Abt__Klimpel
POLY research group offers fellowships for researchers forced to leave Ukraine
The POLY research group on premodern Christianities at Goethe University is offering five fellowships to Ukrainian academics specialised in medieval or early modern history.
FRANKFURT. The
Russian attack on Ukraine is endangering the lives and work of many
researchers. To help some of them to continue their research outside Ukraine,
the “Polycentricity and Plurality of Premodern Christianities” (POLY) research
group, a Centre for Advanced Studies in Humanities funded by the German
Research Foundation, is offering five fellowships. These are intended for
scholars with a doctoral degree who are dealing with medieval or early modern history
and focus especially on religious diversity.
“With this initiative, we at POLY want to
help colleagues from Ukraine forced to flee to safety and to give a stronger
voice to Ukrainian science and research,” says Professor Birgit Emich, chair of
the POLY fellowship programme, summing up the research group’s motivation. For
Emich, who teaches early modern history at Goethe University, the fellowships also
offer great opportunities for research in Frankfurt: “With the help of these
visiting scholars, we aim to develop further partnerships in this region, which
is so rich for the study of religious diversity.”
The fellowships are endowed with €3,000
per month and initially limited to four months. During the funding period, the visiting
Ukrainian scholars will not only be integrated in work within POLY but also
profit from other research infrastructure at Goethe University, notably, the
research alliance “Dynamics of Religion”, co-chaired by Emich and Christian
Wiese, theologian and professor for Jewish studies.
Applications for fellowships are now being
accepted. They are conditional on a completed doctoral degree and an academic
focus on religious plurality in the medieval or early modern period.
Further
information
Professor Birgit Emich
Institute of History
Chair of Early Modern History
Goethe University
Tel.: +49 (0) 69 798-32594
Email: emich@em.uni-frankfurt.de
https://www.geschichte.uni-frankfurt.de/92594738/Polycentricity_and_Plurality_of_Premodern_Christianities__POLY
Editor: Dr. Anke Sauter, Science Editor, PR & Communication Office, Tel. +49 69 798-13066, Fax + 49 69 798-763-12531, sauter@pvw.uni-frankfurt.de