Intensive hunt for drugs to fight COVID-19
The entire world is currently waiting for a vaccine against COVID-19. Intensive research is ongoing to develop useful drugs against the novel coronavirus SARS-CoV-2. At Uppsala Biomedical Centre (BMC), substances are being tested that attack the same type of enzyme as drugs against HIV and hepatitis C.
“We want to develop antiviral drugs that focus on different targets in the virus. We will need several effective drugs, and they should preferably be administered easily in tablet form, not intravenously like the drug Remdesivir,” says Johan Lennerstrand, docent in clinical microbiology at the Department of Medical Sciences.
His research team is focusing on producing substances that can inhibit a unique enzyme, the “main protease”, which is found in the virus but not in human cells.
“Such protease inhibitors have successfully been developed to treat HIV and hepatitis C in the past,” says Lennerstrand, who has been researching drugs for HIV for twenty years and about drugs for hepatitis C for the past ten years.
With the help of research colleagues in Oxford and at Karolinska Institutet (KI), they have gained access to the SARS-CoV-2 protease in its pure form. Their research is initially being conducted at SciLifeLab’s Drug Discovery and Development platform, where they can utilize computer-based virtual screening combined with SciLifeLab’s extremely large substance library.
“These substances are DNA-labelled and act like small Lego pieces. Binding two or three Lego pieces can result in billions of different variations, depending on the size of the library of substances. This is a unique tool, usually only available at large pharmaceutical companies. But now we have access to it, thanks to SciLifeLab.”
Starting point for new drugs
Between the enzyme and the different substances, he expects that they will find several interesting candidates. Once identified, they will continue work with these candidates together with Anja Sandström, a researcher at the Department of Medicinal Chemistry, who has extensive experience developing protease inhibitors against hepatitis C and HIV.
“When we have obtained the first candidates with drug chemistry synthesis, we will test to ensure they are not toxic, partly in enzymatic tests and partly in the biosafety level 3 laboratory here at Zoonosis Science Center. We may be able to contribute a piece of the puzzle together with many other researchers who are doing the same thing internationally. We are developing the starting points from which drugs can be developed.”
In addition to testing that the substances work in cell cultures, it is necessary to check that the drug is absorbed and transported in the body properly and that it is not harmful to the patient. If necessary, small changes need to be made, and this is also something that SciLifeLab can help with, since its mission is to work with both pharmaceutical companies and academic groups to develop potential drugs.
“With some luck, we hope to quickly find promising substances with direct effect on SARS-CoV-2 that can begin clinical studies within two years. Real muscles are needed to do the clinical studies, and that’s the job of pharmaceutical companies. Normally this would take at least five years, but the need is so urgent that an antiviral drug will be created in record time. Several drugs are also needed that attack different targets in the virus.”
Tests existing drugs
They are already testing existing drugs that could treat the novel coronavirus.
“We will also test previous advanced protease inhibitors, such as what the drug company Medivir developed for other viral infections but chose not to proceed with clinical studies. We will study them both enzymatically and in cell culture. We also use computer simulations and have access to enormously powerful computer software through Uppmax and SciLifeLab,” says Lennerstrand.
Zoonosis Science Center (ZSC) at BMC serves as the actual meeting place for the research. They are focusing heavily on research about the corona pandemic. In addition to drugs, they develop tests to investigate the spread of infection and immunity in Sweden.
“Once we realized that the virus had become epidemic in Sweden, that is, that it is something that we will have to deal with for some time, we gradually refocused our research,” says Åke Lundkvist, professor of virology who leads ZSC.
Many different types of expertise
This was facilitated by research funding organisations both in Sweden and the EU approving the use of grants for other projects for research on the novel coronavirus.
ZSC began in autumn 2014 and the following year the biosafety level 3 laboratory at BMC opened. This was in connection with Åke Lundkvist becoming professor at Uppsala University. Lundkvist had previously worked at KI and the Swedish Institute of Infectious Diseases, which later became the Public Health Agency of Sweden.
Together with Björn Olsen, professor of infectious medicine, he has built up a research team with a core of 15–20 people with many different types of expertise.
“In our team, we have virologists, bacteriologists, entomologists, drug experts, veterinarians and medical researchers. What is amazing is that we now have a collection of people in our Zoonosis Lab that is perfect for researching the SARS-CoV-2 virus,” says Lundkvist.
The research mainly focuses on finding and developing tests that detect antibodies to the virus. These are both rapid tests and more advanced tests, and the goal is to create a more realistic picture of the extent of the spread of the virus in Sweden.
Fewer than believed have antibodies
Recently, tests were conducted on 454 individuals in Stockholm. These tests showed that only 7.5 per cent had antibodies, which differed significantly from the calculations made by experts at the Public Health Agency.
“We will wait to say more about how immunity is progressing until we have conducted another round of tests in late May.”
Many people are hoping for flock immunity, but Åke Lundkvist finds it difficult to know what that means in this case.
“No one knows how the spread of the virus will develop and what it takes for flock immunity to kick in. We can only speculate.”
We may have to wait for a vaccine and effective drugs before society can return to normal. One thing is certain: researchers around the world are working hard to solve this challenge.
Tove Hoffman has been awarded funds from the AXA Research Fund
The AXA Research Fund has selected eight research projects to advance scientific knowledge and inform decision-making around the health impact of climate change.
Climate change, according to the World Health Organization (WHO), is the single greatest health threat facing humanity. Climate hazards directly cause over 150,000 deaths annually, and the figure is expected to double by 2030.1 According to the IPCC, if global greenhouse gas emissions continue at their current rate, global warming will exceed 2°C above pre-industrial levels by 2050, with serious consequences for human health including severe dehydration, respiratory diseases, acute cerebrovascular accidents, and thrombogenesis. Furthermore, climate change is one of the most frequently implicated "drivers" of infectious disease threats. More scientific knowledge is urgently required to accelerate awareness and develop effective adaptation and mitigation strategies to preserve planetary and human health.
How fat takes over the lymph nodes as we age
A new study from researchers at Uppsala University presents novel findings on why human lymph nodes lose their function with age and the consequences for the effectiveness of our immune system. The article has been published in The Journal of Pathology.
Kan vi hjälpa barn som drabbats av Sanfilippos sjukdom?
Professor Lena Kjellén vid Uppsala universitet har fått ta del av de pengar som Hjärnfonden delar ut från Team Rynkebys årliga arrangemang Skolloppet. Tillsammans med Anders Dagälv, ST-läkare vid Akademiska sjukhuset, forskar hon på ämnet och försöker hitta ett sätt att behandla Sanfilippos sjukdom.
Atopic dermatitis in dogs linked to certain parts of the genome
Using new gene mapping methods, researchers have found connections between atopic dermatitis (eczema) in dogs and several regions of the genome. Some of the genes identified coincide with genes linked to similar problems in humans. The filaggrin gene region, for example, which is regarded as the most powerful risk factor for atopic eczema in humans, has now also been linked to this disease in Labrador retrievers.
The Marie Skłodowska-Curie Actions Postdoctoral Fellowship
The Marie Skłodowska-Curie fellowship programme is one of the European Union’s flagship programmes for postgraduate and postdoctoral training of researchers.
Gunnar Pejler has been awarded SEK 6 million in research grants from the Erling-Persson stiftelse
Gunnar Pejler has been awarded SEK 1.5 million in research grants from Hjärt-Lungfonden
Åke Lundkvist has been awarded SEK 3 million in laboratory support from SciLifeLab
Åke Lundkvist has been awarded SEK 3 million in laboratory support from SciLifeLab for the period 2023 - 2024 for the project ZSC – National core facility for Pandemic Preparedness
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Group Sellin receives the Swedish Research Council Consolidator Grant 2022
Mikael Sellin’s research group has been awarded the Swedish Research Council Consolidator Grant. The grant, amounting to 10 million SEK over 5 years, aims “…to give the most prominent junior researchers the opportunity to consolidate their research and broaden their activities as independent researchers.”
Jin-ping Li has been granted proof of concept grants by the Swedish Research Council
Grant decision has been made by The Swedish Research Council on proof of concept within the infection area 2022. In total, nearly 20 million SEK for 2022–2024.
Maria Letizia Di Martino has been awarded a Carl Tryggers Stiftelse Research Grant
Maria Letizia Di Martino has been awarded 444,000 SEK by the Carl Tryggers Stiftelse for the project “The fitness landscape of Shigella flexneri at the transition between environmental and host-colonizing lifestyles”.
Researchers at IMBIM are awarded a total of 23.4 million by the Swedish Research Council for the grant period 2022-2027
The Swedish Research Council has decided which applications will be granted grants in medicine and health in 2022. A total of just over SEK 1.2 billion will be granted for the years 2022–2027.
Researchers at IMBIM are awarded a total of SEK 12,3 million in research grants from Cancerfonden
Cancerfonden´s research committee has this year decided to distribute SEK 900 million to 230 research projects.
Widespread variation of inherited retroviruses among Darwin’s finches
Vertebrate genomes are repositories for retrovirus code that was deposited into germ line as inherited endogenous retroviruses during evolution. Researchers from Uppsala University and Princeton University now provide new findings about retroviral establishment and distribution among Darwin’s finches. The findings are being published in Nature Communications.
Cancervaccin på gränsen till genombrott
Utvecklingen av cancervaccin kan snabbas på tack vare den internationella kraftsamling som gjordes för att framställa covid-19-vaccin. På sikt kan cancerformer som i dag saknar bot bli möjliga att behandla. Men vad är egentligen ett cancervaccin?
How innovation from Uppsala University can reduce antibiotic-resistant bacteria
Treating severe infections with a combination of antibiotics has long been standard practice in Swedish medicine. Despite this, at present there is no clinical test to prove how well it actually works. Researcher Nikos Fatsis-Kavalopoulos wants to change that.
New inherited retroviruses identified in the koala genome
Historic virus infections can be traced in vertebrate genomes. For millions of years, these genomes have been repositories for retroviruses that incorporated their code into germline cells and were inherited as endogenous retroviruses (ERVs). Researchers from Uppsala University now provide new findings about retroviral establishment in the koala genome. The findings are being published in the journal PNAS.
Inês Rodrigues Faria, master student at IMBIM, received the best short oral presentation award at the 11th One Health Sweden Scientific Meeting "Pandemics and preparedness", March 2022.
Erik Schubert, PhD student at IMBIM, has received an award for best post at the scientific conference Viruses 2022
Erik Schubert presented results on how human adenovirus can affect homeostasis in mitochondria, focusing on which viral protein may be responsible for mitochondrial DNA release.
Ancient Genes for Symbiosis Hint at Mitochondria’s Origins
Ancestors of legionella bacteria infected cells two billion years ago
Researchers at Uppsala University have discovered that the ancestors of legionella bacteria infected eukaryotic cells as early as two billion years ago. It happened soon after eukaryotes began to feed on bacteria. These results, described in a new study published in Molecular Biology and Evolution, also contribute to the chicken-or-egg debate about whether mitochondria or phagocytosis came first.
The Swedish Society for Virology has decided that the first Sigvard Olofsson Award in virology is to be shared between Mahmoud M Naguib at IMBIM and Ka-Wei Tang at Sahlgrenska Academy
Herring and sprat: silver of the sea that turned into sand
“I’m passionate about understanding the genetic background of biodiversity development and I’d like our research to culminate in more sustainable use of herring and sprat, which are a superb resource,” writes Leif Andersson, Professor of Functional Genomics at IMBIM.
Johanna Lindahl has been awarded about 3 million in research grants from Formas.
Researchers at IMBIM are awarded a total of SEK 20 million in research grants from Cancerfonden
Cancerfonden´s research committee has decided to distribute SEK 732 million to 230 research projects. In total this year, there will be SEK 850 million for Swedish cancer research.
För andra året i rad har medicinska studierådet utsett IMBIM´s kurs medicinsk mikrobiologi till bästa kurs på läkarprogrammet.
Örjan Carlborg, Lionel Guy, Jenny Hesson, Diarmaid Hughes, Mahmoud Naguib and Linus Sandegren have been awarded SEK 2.8 million för the coming four years
Carl-Johan Rubin has been awarded NOK 3 120 000 by Havforskningsinstitutet for the next four years.
Dan Andersson, Patric Jern, Nils Landegren and Jin-ping Li are awarded a total of 21.8 million SEK by the Swedish Research Council for the grant period 2021-2025
Why some Darwin’s finch nestlings have yellow beaks
Allergisk stimulans aktiverar förstadieceller till mastceller
Dan I Andersson har tilldelas medel om 2 025 000 dollar över fem år från amerikanska National Institutes of Health (NIH)
Gut epithelium muscles up against infection
Nils Landegren tilldelas Stora Gustafsson priset 2021
Påskkaninen som kan gå på ”händerna”
Mastcellers frisättning av serotonin bidrar till luftvägsöverkänslighet vid astma
Over half a billion people a year get some type of bacterial intestinal infection. By building their own intestines, so-called organoids, Mikael Sellin and his colleagues at IMBIM, Uppsala University can study how these infections occur.
Antibiotic resistance from random DNA sequences
Genome sequencing for more sustainable herring fishery
Linnémedaljen tilldelas professor Kerstin Lindblad Toh
Stora bidrag till utveckling av forskningsinfrastruktur. Kerstin Lindblad-Toh tilldelas 7 850 000 kr för sitt projekt En svensk EBP plattform: infrastruktur och proof-of-principle project
Carl-Henrik Heldin, Per Jemth, Joakim Näsvall and Gunnar Pejler are awarded a total of 14.2 million by the Swedish Research Council for the grant period 2020-2024.
Rapid testing for antibiotic resistance
In cases of severe infection, identifying the correct antibiotic – and doing so quickly – can be a matter of life and death. At Uppsala University a very fast test for antibiotic resistance is being developed. The goal is to reduce the time from taking a sample to getting a result from one day to under four hours.
240 mammals help us understand the human genome
A large international consortium led by scientists at Uppsala University and the Broad Institute of MIT and Harvard has sequenced the genome of 130 mammals and analysed the data together with 110 existing genomes to allow scientist to identify which are the important positions in the DNA. This new information can help both research on disease mutations in humans and how best to preserve endangered species. The study is published in Nature.
Per Jemth, Lena Kjellén, Kerstin Lindblad-Toh och Anna-Karin Olsson tilldelas 11 miljoner i forskningsanslag av Cancerfonden
Carl-Henric Heldin, Per Jemth, Joakim Näsvall, John Pettersson och Gunnar Pejler har tilldelats projekt/etableringsbidrag på totalt ca 20 miljoner över fyra år av Vetenskapsrådet.
Vetenskapsrådet har fattat beslut om vilka ansökningar som beviljats bidrag inom Naturvetenskap och teknikvetenskap 2020. Uppsala universitet får 225 miljoner till 65 forskningsprojekt som spänner över ett brett fält av områden
Leif Andersson receives 25 million SEK in project grants from KAW
New high-speed test shows how antibiotics combine to kill bacteria
Researchers at Uppsala University have developed a new method to determine – rapidly, easily and cheaply – how effective two antibiotics combined can be in stopping bacterial growth. The new method is simple for laboratories to use and can provide greater scope for customising treatment of bacterial infections. The study is published in PLOS Biology.
Genomic Analysis Reveals Many Animal Species May Be Vulnerable to SARS-CoV-2 Infection
För att i framtiden snabbt kunna hejda utbrott av covid-19 som orsakas av viruset SARS-CoV-2 och för att redan nu kunna skydda utrotningshotade arter som riskerar att drabbas, behövs kunskap om vilka djur som är tänkbara smittbärare av viruset. Professor Kerstin Lindblad-Toh vid Uppsala universitet och hennes kollegor har identifierat ett stort antal däggdjur som potentiellt kan smittas.