Research group - Ali Mirazimi
In our research programmes, we will i) investigate the molecular pathogenesis mechanism of haemorrhagic fever (VHF) diseases such as Crimean Congo haemorrhagic fever Virus (CCHFV) and Ebola Disease Virus (EBOV), ii) developing antiviral against SARS-CoV2 and VHF, iii) developing vaccine against CCHFV and also agains SARS-CoV2.
Molecular pathogenesis mechanism of haemorrhagic fever (VHF)
Increased mobility in the general population and recent climate changes affecting the geographical distribution of viral vectors, combined with animal trade, immigrations and augmented bioterrorism threats, have heightened the risk of emerging viral diseases in Europe. These changing factors highlight the need for understanding the interactions between virus-vector-animal-human in the infection cycle and for the development of new countermeasures such as antivirals and vaccines. Knowledge regarding the pathogenesis of highly emerging viruses such as Viral Hemorrhagic Fever (VHF) is very limited and in some cases completely lacking. VHF diseases are caused by a diverse set of pathogens belonging to different virus families. Some of these viruses cause very severe diseases, with fatal outcomes.
It is obvious that the knowledge of virus biology, pathogenesis, vaccine development and therapeutics is highly limited for these important bio-threat. To achieve a globally effective health programme for this disease, there is a need for synergised national and international programmes with the capability to perform modern and advanced research. Our projects are focused on multinational/institutional collaboration. The major focus of our projects are i) understanding of the role of innate immune response to molecular pathogenesis of these diseases, ii) to understand Virus-Host cell interaction (animal, insects and human cells), iii) developing vaccines against emerging viral diseases, iv) developing new therapeutic tools against emerging viral diseases and v). Developing new diagnostic tools.
Developing antiviral against SARS-CoV2
We are coordinating an IMI/H2020 joint research project with focus on developing antiviral against sars-cov2. The sars-cov-2 pandemic has become an unprecedented burden to public health, our civil societies and the global economy providing frontline therapies for covid-19 and future corona virus outbreaks requires a concerted effort of different disciplines, technologies, high security labs, and rapid translation of scientific findings to industrials. Our team is establishing state-of-the-art infection model system; engineered human 3D organoids. Furthermore we are investigating the antiviral activity of recombinant soluble human angiotensin-converting enzyme 2 (srhace-2). In addition, we aim to identify and characterize new essential host cell factors for sars-cov-2 and other corona viruses with pandemic potential.
Developing Vaccine
Our lab are coordinating an international consortium called CCHFVaccine. Our goal is o develop a vaccine against CCHFV, We have established several platform for developiong a vaccine against CCHFV from Adenovirus platform to genetic vaccine platform mRNA and DNA. Several of outcome of this project has been published in high impact peer review journals. www.CCHFVACCINE.eu
Our lab is also partner of OPENCORONA project (H2020 supported joint research project, coordinates from Karolinska Institute, Prof Matti Sällberg). The project aims to bring a new generation vaccine protecting against SARS-CoV2 different variants.
https://ki.se/en/research/opencorona
Developing antiviral against SARS-CoV2
We are coordinating an IMI/H2020 joint research project with focus on developing antiviral against sars-cov2. The sars-cov-2 pandemic has become an unprecedented burden to public health, our civil societies and the global economy providing frontline therapies for covid-19 and future corona virus outbreaks requires a concerted effort of different disciplines, technologies, high security labs, and rapid translation of scientific findings to industrials. Our team is establishing state-of-the-art infection model system; engineered human 3D organoids. Furthermore we are investigating the antiviral activity of recombinant soluble human angiotensin-converting enzyme 2 (srhace-2). In addition, we aim to identify and characterize new essential host cell factors for sars-cov-2 and other corona viruses with pandemic potential.
Our lab is partner of OPENCORONA project (H2020 supported joint research project, coordinates from Karolinska Institute, Prof Matti Sällberg). The project aims to bring a new generation vaccine protecting against SARS-CoV2 different variants.
https://ki.se/en/research/opencorona
Research group leader
Ali Mirazimi
Adjunct professorSamir Abdurahman
FolkhälsomyndighetenKlara Andersson
Ph.D student, Karolinska InstituteSofia Appelberg
Post Doc, FolkhälsomyndighetenStephanie Devignot
Postdoctoral researcherElizabeth Elder
Researcher, National Veterinary Institute (SVA)Lijo Johan
Post Doc, National Veterinary Institute (SVA)Caroline Vernersson
BMA, SVA, UppsalaExternal funding
Swedish research Council, 2018-2025.
European Commission. H2020, 2017-2023.
Initiative medicine innovation funds, 20120-2024.
Swedish foundation for Strategic Research, 2022-2026.
The Swedish foundation for International cooperation in research and higher education, 2015-2023.
Collaborations
Professor Friedemann Weber, Germany (Vaccine development and molecular pathogenesis)
Professor Josef Penninger, Austria (Virus-host interaction)
Professor Drew Weismann (university of Pennsylvevina)
Professor Heinrich Feldmann, NIAID, NIH, (Vaccine development and molecular pathogenesis)
Professor Yee-Joo Tan, Singapore (Molecular pathogenesis)
Professor Martin Groushop, Germany, (Vaccine development)
Professor, Matti Sällberg, LABMED, KI, (Vaccine development)
Associate professor, Ujjwal Neogi, Karolinska Institute
Professor Nazif Elaldi, Turkey, (Vaccine development)
Professor Anna Papa, Greece, (Virus epidemiology and Diagnostic)
Professor. Amadou Sall, Pasture Dakar, (Diagnostic)
Professor. Noel Tordo, Pasture Guinea (Epidemiology and diagnostic)
Selected publications
Identification of CCZ1 as an essential lysosomal trafficking regulator in Marburg and Ebola virus infections.
Monteil V, Kwon H, John L, Salata C, Jonsson G, Vorrink SU, Appelberg S, Youhanna S, Dyczynski M, Leopoldi A, Leeb N, Volz J, Hagelkruys A, Kellner MJ, Devignot S, Michlits G, Foong-Sobis M, Weber F, Lauschke VM, Horn M, Feldmann H, Elling U, Penninger JM, Mirazimi A
Nat Commun 2023 Oct;14(1):6785
Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2.
Monteil V, Kwon H, Prado P, Hagelkrüys A, Wimmer RA, Stahl M, Leopoldi A, Garreta E, Hurtado Del Pozo C, Prosper F, Romero JP, Wirnsberger G, Zhang H, Slutsky AS, Conder R, Montserrat N, Mirazimi A, Penninger JM
Cell 2020 May;181(4):905-913.e7
Human soluble ACE2 improves the effect of remdesivir in SARS-CoV-2 infection.
Monteil V, Dyczynski M, Lauschke VM, Kwon H, Wirnsberger G, Youhanna S, Zhang H, Slutsky AS, Hurtado Del Pozo C, Horn M, Montserrat N, Penninger JM, Mirazimi A
EMBO Mol Med 2021 Jan;13(1):e13426
A DNA-based vaccine protects against Crimean-Congo haemorrhagic fever virus disease in a Cynomolgus macaque model.
Hawman DW, Ahlén G, Appelberg KS, Meade-White K, Hanley PW, Scott D, Monteil V, Devignot S, Okumura A, Weber F, Feldmann H, Sällberg M, Mirazimi A
Nat Microbiol 2021 Feb;6(2):187-195
Nucleoside-Modified mRNA Vaccines Protect IFNAR-/- Mice against Crimean-Congo Hemorrhagic Fever Virus Infection.
Appelberg S, John L, Pardi N, Végvári Á, Bereczky S, Ahlén G, Monteil V, Abdurahman S, Mikaeloff F, Beattie M, Tam Y, Sällberg M, Neogi U, Weissman D, Mirazimi A
J Virol 2022 Feb;96(3):e0156821
Multi-omics insights into host-viral response and pathogenesis in Crimean-Congo hemorrhagic fever viruses for novel therapeutic target.
Neogi U, Elaldi N, Appelberg S, Ambikan A, Kennedy E, Dowall S, Bagci BK, Gupta S, Rodriguez JE, Svensson-Akusjärvi S, Monteil V, Vegvari A, Benfeitas R, Banerjea A, Weber F, Hewson R, Mirazimi A
Elife 2022 Apr;11():
Genome-wide spatial expression profiling in formalin-fixed tissues.
Gracia Villacampa E, Larsson L, Mirzazadeh R, Kvastad L, Andersson A, Mollbrink A, Kokaraki G, Monteil V, Schultz N, Appelberg KS, Montserrat N, Zhang H, Penninger JM, Miesbach W, Mirazimi A, Carlson J, Lundeberg J
Cell Genom 2021 Dec;1(3):100065
Organoid modeling of Zika and herpes simplex virus 1 infections reveals virus-specific responses leading to microcephaly.
Krenn V, Bosone C, Burkard TR, Spanier J, Kalinke U, Calistri A, Salata C, Rilo Christoff R, Pestana Garcez P, Mirazimi A, Knoblich JA
Cell Stem Cell 2021 Aug;28(8):1362-1379.e7
Induction of caspase activation and cleavage of the viral nucleocapsid protein in different cell types during Crimean-Congo hemorrhagic fever virus infection.
Karlberg H, Tan YJ, Mirazimi A
J Biol Chem 2011 Feb;286(5):3227-34
The DEVD motif of Crimean-Congo hemorrhagic fever virus nucleoprotein is essential for viral replication in tick cells.
Salata C, Monteil V, Karlberg H, Celestino M, Devignot S, Leijon M, Bell-Sakyi L, Bergeron É, Weber F, Mirazimi A
Emerg Microbes Infect 2018 Nov;7(1):190
Virus-Derived DNA Forms Mediate the Persistent Infection of Tick Cells by Hazara Virus and Crimean-Congo Hemorrhagic Fever Virus.
Salvati MV, Salaris C, Monteil V, Del Vecchio C, Palù G, Parolin C, Calistri A, Bell-Sakyi L, Mirazimi A, Salata C
J Virol 2021 Nov;95(24):e0163821
Ebola virus disease: societal challenges and new treatments.
Mirazimi A
J. Intern. Med. 2015 Sep;278(3):227-37
Structure of Crimean-Congo hemorrhagic fever virus nucleoprotein: superhelical homo-oligomers and the role of caspase-3 cleavage.
Wang Y, Dutta S, Karlberg H, Devignot S, Weber F, Hao Q, et al
J. Virol. 2012 Nov;86(22):12294-303
Interferon and cytokine responses to Crimean Congo hemorrhagic fever virus; an emerging and neglected viral zonoosis.
Weber F, Mirazimi A
Cytokine Growth Factor Rev. ;19(5-6):395-404
Development and deployment of a rapid recombinase polymerase amplification Ebola virus detection assay in Guinea in 2015.
Faye O, Faye O, Soropogui B, Patel P, El Wahed AA, Loucoubar C, et al
Euro Surveill. 2015 ;20(44):
Crimean-Congo hemorrhagic fever virus infection is lethal for adult type I interferon receptor-knockout mice.
Bereczky S, Lindegren G, Karlberg H, Akerström S, Klingström J, Mirazimi A
J Gen Virol 2010 Jun;91(Pt 6):1473-7
Production, purification and immunogenicity of recombinant Ebola virus proteins - A comparison of Freund's adjuvant and adjuvant system 03.
Melén K, Kakkola L, He F, Airenne K, Vapalahti O, Karlberg H, et al
J. Virol. Methods 2017 04;242():35-45
Amiodarone and metabolite MDEA inhibit Ebola virus infection by interfering with the viral entry process.
Salata C, Baritussio A, Munegato D, Calistri A, Ha HR, Bigler L, et al
Pathog Dis 2015 Jul;73(5):
Dual effect of nitric oxide on SARS-CoV replication: viral RNA production and palmitoylation of the S protein are affected.
Akerström S, Gunalan V, Keng CT, Tan YJ, Mirazimi A
Virology 2009 Dec;395(1):1-9
Amino acids 15-28 in the ectodomain of SARS coronavirus 3a protein induces neutralizing antibodies.
Akerström S, Tan YJ, Mirazimi A
FEBS Lett. 2006 Jul;580(16):3799-803
An antibody against a novel and conserved epitope in the hemagglutinin 1 subunit neutralizes numerous H5N1 influenza viruses.
Oh HL, Akerström S, Shen S, Bereczky S, Karlberg H, Klingström J, et al
J. Virol. 2010 Aug;84(16):8275-86
Amiodarone and metabolite MDEA inhibit Ebola virus infection by interfering with the viral entry process.
Salata C, Baritussio A, Munegato D, Calistri A, Ha HR, Bigler L, et al
Pathog Dis 2015 Jul;73(5):
Development and deployment of a rapid recombinase polymerase amplification Ebola virus detection assay in Guinea in 2015.
Faye O, Faye O, Soropogui B, Patel P, El Wahed AA, Loucoubar C, et al
Euro Surveill. 2015 ;20(44):
News
He is fighting the new coronavirus
Virus researcher Ali Mirazimi has dedicated himself full-time to the coronavirus since the outbreak of the pandemic in the beginning of 2020.