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Johansson, Emil
Publications (10 of 11) Show all publications
Johansson, E., Caraballo, R., Zocher, G., Mistry, N., Arnberg, N., Stehle, T. & Elofsson, M. (2022). Exploring divalent conjugates of 5-N-acetyl-neuraminic acid as inhibitors of coxsackievirus A24 variant (CVA24v) transduction. RSC Advances, 12(4), 2319-2331
Open this publication in new window or tab >>Exploring divalent conjugates of 5-N-acetyl-neuraminic acid as inhibitors of coxsackievirus A24 variant (CVA24v) transduction
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2022 (English)In: RSC Advances, E-ISSN 2046-2069, Vol. 12, no 4, p. 2319-2331Article in journal (Refereed) Published
Abstract [en]

Coxsackievirus A24 variant (CVA24v) is responsible for several outbreaks and two pandemics of the highly contagious eye infection acute hemorrhagic conjunctivitis (AHC). Currently, neither prevention (vaccines) nor treatments (antivirals) are available for combating this disease. CVA24v attaches to cells by binding Neu5Ac-containing glycans on the surface of cells which facilitates entry. Previously, we have demonstrated that pentavalent Neu5Ac conjugates attenuate CVA24v infection of human corneal epithelial (HCE) cells. In this study, we report on the structure-based design of three classes of divalent Neu5Ac conjugates, with varying spacer lengths, and their effect on CVA24v transduction in HCE cells. In relative terms, the most efficient class of divalent Neu5Ac conjugates are more efficient than the pentavalent Neu5Ac conjugates previously reported.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2022
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-192370 (URN)10.1039/d1ra08968d (DOI)000742407000001 ()2-s2.0-85123934421 (Scopus ID)
Funder
Knut and Alice Wallenberg Foundation, 2013.0019
Available from: 2022-02-11 Created: 2022-02-11 Last updated: 2022-09-15Bibliographically approved
Beyer, S., Kimani, M., Zhang, Y., Verhassel, A., Sternbæk, L., Wang, T., . . . Stollenwerk, M. M. (2022). Fluorescent Molecularly Imprinted Polymer Layers against Sialic Acid on Silica-Coated Polystyrene Cores — Assessment of the Binding Behavior to Cancer Cells. Cancers, 14(8), Article ID 1875.
Open this publication in new window or tab >>Fluorescent Molecularly Imprinted Polymer Layers against Sialic Acid on Silica-Coated Polystyrene Cores — Assessment of the Binding Behavior to Cancer Cells
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2022 (English)In: Cancers, ISSN 2072-6694, Vol. 14, no 8, article id 1875Article in journal (Refereed) Published
Abstract [en]

Sialic acid (SA) is a monosaccharide usually linked to the terminus of glycan chains on the cell surface. It plays a crucial role in many biological processes, and hypersialylation is a common feature in cancer. Lectins are widely used to analyze the cell surface expression of SA. However, these protein molecules are usually expensive and easily denatured, which calls for the development of alternative glycan-specific receptors and cell imaging technologies. In this study, SA-imprinted fluorescent core-shell molecularly imprinted polymer particles (SA-MIPs) were employed to recognize SA on the cell surface of cancer cell lines. The SA-MIPs improved suspensibility and scattering properties compared with previously used core-shell SA-MIPs. Although SA-imprinting was performed using SA without preference for the α2,3-and α2,6-SA forms, we screened the cancer cell lines analyzed using the lectins Maackia Amurensis Lectin I (MAL I, α2,3-SA) and Sambucus Nigra Lectin (SNA, α2,6-SA). Our results show that the selected cancer cell lines in this study presented a varied binding behavior with the SA-MIPs. The binding pattern of the lectins was also demonstrated. Moreover, two different pentavalent SA conjugates were used to inhibit the binding of the SA-MIPs to breast, skin, and lung cancer cell lines, demonstrating the specificity of the SA-MIPs in both flow cytometry and confocal fluorescence microscopy. We concluded that the synthesized SA-MIPs might be a powerful future tool in the diagnostic analysis of various cancer cells.

Place, publisher, year, edition, pages
MDPI, 2022
Keywords
cancer, imprinting, molecularly imprinted polymers, SA conjugates, sialic acid
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-194273 (URN)10.3390/cancers14081875 (DOI)000786858400001 ()2-s2.0-85127781436 (Scopus ID)
Available from: 2022-04-29 Created: 2022-04-29 Last updated: 2023-09-05Bibliographically approved
Johansson, E., Caraballo, R., Hurdiss, D. L., Mistry, N., Andersson, C. D., Thompson, R. F., . . . Elofsson, M. (2021). Exploring the effect of structure-based scaffold hopping on the inhibition of coxsackievirus a24v transduction by pentavalent n-acetylneuraminic acid conjugates. International Journal of Molecular Sciences, 22(16), Article ID 8418.
Open this publication in new window or tab >>Exploring the effect of structure-based scaffold hopping on the inhibition of coxsackievirus a24v transduction by pentavalent n-acetylneuraminic acid conjugates
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2021 (English)In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, no 16, article id 8418Article in journal (Refereed) Published
Abstract [en]

Coxsackievirus A24 variant (CVA24v) is the primary causative agent of the highly contagious eye infection designated acute hemorrhagic conjunctivitis (AHC). It is solely responsible for two pandemics and several recurring outbreaks of the disease over the last decades, thus affecting millions of individuals throughout the world. To date, no antiviral agents or vaccines are available for combating this disease, and treatment is mainly supportive. CVA24v utilizes Neu5Ac-containing glycans as attachment receptors facilitating entry into host cells. We have previously reported that pentavalent Neu5Ac conjugates based on a glucose-scaffold inhibit CVA24v infection of human corneal epithelial cells. In this study, we report on the design and synthesis of scaffold-replaced pentavalent Neu5Ac conjugates and their effect on CVA24v cell transduction and the use of cryogenic electron microscopy (cryo-EM) to study the binding of these multivalent conjugates to CVA24v. The results presented here provide insights into the development of Neu5Ac-based inhibitors of CVA24v and, most significantly, the first application of cryo-EM to study the binding of a multivalent ligand to a lectin.

Place, publisher, year, edition, pages
MDPI, 2021
Keywords
5-N-acetylneuraminic acid, Antivirals, Conjunctivitis, Coxsackievirus A24v, Cryo-EM, Multivalency, Sialic acid conjugates
National Category
Microbiology in the medical area Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-186555 (URN)10.3390/ijms22168418 (DOI)000689130700001 ()2-s2.0-85111762142 (Scopus ID)
Available from: 2021-08-11 Created: 2021-08-11 Last updated: 2023-09-05Bibliographically approved
El-Schich, Z., Zhang, Y., Göransson, T., Dizeyi, N., Persson, J. L., Johansson, E., . . . Wingren, A. G. (2021). Sialic acid as a biomarker studied in breast cancer cell lines in vitro using fluorescent molecularly imprinted polymers. Applied Sciences, 11(7), Article ID 3256.
Open this publication in new window or tab >>Sialic acid as a biomarker studied in breast cancer cell lines in vitro using fluorescent molecularly imprinted polymers
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2021 (English)In: Applied Sciences, E-ISSN 2076-3417, Vol. 11, no 7, article id 3256Article in journal (Refereed) Published
Abstract [en]

Sialylations are post-translational modifications of proteins and lipids that play important roles in many cellular events, including cell-cell interactions, proliferation, and migration. Tumor cells express high levels of sialic acid (SA), which are often associated with the increased invasive potential in clinical tumors, correlating with poor prognosis. To overcome the lack of natural SA-receptors, such as antibodies and lectins with high enough specificity and sensitivity, we have used molecularly imprinted polymers (MIPs), or “plastic antibodies”, as nanoprobes. Because high expression of epithelial cell adhesion molecule (EpCAM) in primary tumors is often associated with proliferation and a more aggressive phenotype, the expression of EpCAM and CD44 was initially analyzed. The SA-MIPs were used for the detection of SA on the cell surface of breast cancer cells. Lectins that specifically bind to the a-2,3 SA and a-2,6 SA variants were used for analysis of SA expression, with both flow cytometry and confocal microscopy. Here we show a correlation of EpCAM and SA expression when using the SA-MIPs for detection of SA. We also demonstrate the binding pattern of the SA-MIPs on the breast cancer cell lines using confocal microscopy. Pre-incubation of the SA-MIPs with SA-derivatives as inhibitors could reduce the binding of the SA-MIPs to the tumor cells, indicating the specificity of the SA-MIPs. In conclusion, the SA-MIPs may be a new powerful tool in the diagnostic analysis of breast cancer cells.

Place, publisher, year, edition, pages
MDPI, 2021
Keywords
Breast cancer, Epithelial cell adhesion molecule, Molecularly imprinted polymers, Nanoparticles, Sialic acid
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-182753 (URN)10.3390/app11073256 (DOI)000638354600001 ()2-s2.0-85104259855 (Scopus ID)
Available from: 2021-05-24 Created: 2021-05-24 Last updated: 2023-09-05Bibliographically approved
Johansson, E., Caraballo, R. & Elofsson, M. (2021). Synthesis of 4-O-alkylated N-acetylneuraminic acid derivatives. Journal of Organic Chemistry, 86(13), 9145-9154
Open this publication in new window or tab >>Synthesis of 4-O-alkylated N-acetylneuraminic acid derivatives
2021 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 86, no 13, p. 9145-9154Article in journal (Refereed) Published
Abstract [en]

The synthesis of 4-O-alkyl analogs of N-acetylneuraminic acid (Neu5Ac) and the scope of the reaction are described. Activated alkyl halides and sulfonates and primary alkyl iodides give products in useful yields. The utility of the methodology is exemplified using a thiophenyl Neu5Ac building block to synthesize a 4-O-alkyl DANA analog. These results expand the toolbox of Neu5Ac chemistry with value in drug discovery and for the design of novel tools to study the biology of Neu5Ac lectins. 

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2021
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
urn:nbn:se:umu:diva-182319 (URN)10.1021/acs.joc.1c00235 (DOI)000670661000052 ()34138565 (PubMedID)2-s2.0-85110169034 (Scopus ID)
Funder
Knut and Alice Wallenberg Foundation, 2013.0019
Available from: 2021-04-19 Created: 2021-04-19 Last updated: 2024-01-03Bibliographically approved
Johansson, E. (2021). Tailored conjugates of N-acetylneuraminic acid and small molecules that block virus cell attachment and entry. (Doctoral dissertation). Umeå: Umeå Universitet
Open this publication in new window or tab >>Tailored conjugates of N-acetylneuraminic acid and small molecules that block virus cell attachment and entry
2021 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Viruses are obligate intracellular parasites, unable to replicate without exploiting machinery andmaterials from host cells. Pandemics of viral diseases have had large impacts on human socieities and are continued threats to global health. The most efficient means of controlling viral diseases are preventive measures such as immunization of the population, social distancing, and basic hygiene routines. Another mean is development of antiviral drugs that could be used as preventive measures and in treatment of infected individuals. Coxsackievirus A24 variant (CVA24v) is a highly contagious pathogen that cause large outbreaks and pandemics of the eye infection acute hemorrhagic conjunctivitis. Human adenovirus D species type 37 (HAdV-D37) causes epidemics of the severe eye infection epidemic keratoconjunctivitis, that can become life-threatening in immunocompromised individuals. Currently, no specific treatments (vaccine or antivirals) are available to combat the diseases caused by these two pathogens.

CVA24v and HAdV-D37 bind to N-acetylneuraminic acid (Neu5Ac) glycans on host cells facilitating attachment and subsequent infection. In this thesis, we explored inhibition of this common recognition motif by development of pentavalent Neu5Ac containing molecules with radial topology to act as decoy receptors. This allowed us to study the potential of development of a general inhibitor targeting both these viruses. The developed compounds inhibited attachment of CVA24v and HAdVD37 to cells.

Furthermore, we developed divalent Neu5Ac tools to validate if targeting the Neu5Acmediated attachment of CVA24v to cells were a potential target for antiviral drug discovery and development. The results from these studies indicate that development of a Neu5Ac-based antiviral targeting CVA24v looks bleak as the primary receptor utilized by this virus is ICAM-1. The work with developing Neu5Ac tools led to a side project with synthesis of 4-O-alkyl Neu5Ac analogs. In this project we provided a method to synthesize 4-O-alkyl analogs of Neu5Ac and gave insights into the scope of the reaction. This work could have have value in drug discovery.

Targeting enterovirus uncoating is a well explored strategy for the inhibition of enterovirus infection. In this thesis, we synthezied novel branched probes of pleconaril (a well-known pocket binding molecule) to study if targeting the unique branched pocket of CVA24v could have potential as a target for antiviral drug discovery. Further experiments are needed to draw conclusions in regards to the future prospects of targeting this unique feature.

At last, two novel classes of trivalent Neu5Ac conjugates were develop using a structure-based approach targeting HAdV-D37, -D36, and -D26. This led to a more potent compound towards HAdVD37 further validating that targeting the attachment of this virus to cells is a reasonable strategy for antiviral drug development. Towards HAdV-D26 the inhibitory effect was saturated at 50%, likely due to engagement of other receptors. Evaluation towards HAdV-D36 is currently ongoing. Structural biology studies, indicates the compounds bind to the viruses via chelation of their trimeric binding sites. Taken together, these compounds have potential to be used as chemical tools to study the biology of human adenoviruses and perhaps other Neu5Ac binding proteins.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2021. p. 91
Keywords
N-acetylneuraminic acid, Neu5Ac, sialic acid, multivalency, Coxsackievirus A24v (CVA24v), Human adenovirus D37, D36, D26, (HAdV-D37, HAdV-D26, HAdV-D36), 4-O-alkyl Neu5Ac, cryo-EM, branched pleconaril probes, conjunctivitis
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
urn:nbn:se:umu:diva-182411 (URN)978-91-7855-567-3 (ISBN)978-91-7855-566-6 (ISBN)
Public defence
2021-05-21, KBC Glasburen, Kemiskt Biologiskt Centrum, Umeå, 09:00 (English)
Opponent
Supervisors
Note

Titel på omslaget: Tailored conjugates of N-acetylneuraminic acid and small molecules that block virus attachment and entry

Available from: 2021-04-30 Created: 2021-04-21 Last updated: 2023-03-16Bibliographically approved
Johansson, E., Caraballo, R., Mistry, N., Zocher, G., Qian, W., Andersson, C. D., . . . Elofsson, M. (2020). Pentavalent Sialic Acid Conjugates Block Coxsackievirus A24 Variant and Human Adenovirus Type 37-Viruses That Cause Highly Contagious Eye Infections. ACS Chemical Biology, 15(10), 2683-2691
Open this publication in new window or tab >>Pentavalent Sialic Acid Conjugates Block Coxsackievirus A24 Variant and Human Adenovirus Type 37-Viruses That Cause Highly Contagious Eye Infections
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2020 (English)In: ACS Chemical Biology, ISSN 1554-8929, E-ISSN 1554-8937, Vol. 15, no 10, p. 2683-2691Article in journal (Refereed) Published
Abstract [en]

Coxsackievirus A24 variant (CVA24v) and human adenovirus 37 (HAdV-37) are leading causative agents of the severe and highly contagious ocular infections acute hemorrhagic conjunctivitis and epidemic keratoconjunctivitis, respectively. Currently, neither vaccines nor antiviral agents are available for treating these diseases, which affect millions of individuals worldwide. CVA24v and HAdV-37 utilize sialic acid as attachment receptors facilitating entry into host cells. Previously, we and others have shown that derivatives based on sialic acid are effective in preventing HAdV-37 binding and infection of cells. Here, we designed and synthesized novel pentavalent sialic acid conjugates and studied their inhibitory effect against CVA24v and HAdV-37 binding and infection of human corneal epithelial cells. The pentavalent conjugates are the first reported inhibitors of CVA24v infection and proved efficient in blocking HAdV-37 binding. Taken together, the pentavalent conjugates presented here form a basis for the development of general inhibitors of these highly contagious ocular pathogens.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2020
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-176796 (URN)10.1021/acschembio.0c00446 (DOI)000582580100008 ()32845119 (PubMedID)2-s2.0-85093538705 (Scopus ID)
Available from: 2020-11-24 Created: 2020-11-24 Last updated: 2023-03-24Bibliographically approved
Johansson, E., Caraballo, R., Zocher, G., Mistry, N., Arnberg, N., Stehle, T. & Elofsson, M.Exploring divalent conjugates of 5-N-acetyl-neuraminic acid as inhibitors of coxsackievirus A24 variant (CVA24v) transduction.
Open this publication in new window or tab >>Exploring divalent conjugates of 5-N-acetyl-neuraminic acid as inhibitors of coxsackievirus A24 variant (CVA24v) transduction
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Organic Chemistry Biological Sciences
Identifiers
urn:nbn:se:umu:diva-182331 (URN)
Available from: 2021-04-19 Created: 2021-04-19 Last updated: 2021-04-21
Johansson, E., Caraballo, R., Hurdiss, D. L., Mistry, N., Andersson, D. C., Thompson, R. F., . . . Elofsson, M.Exploring the effect of rational scaffold hopping on the inhibition of coxsackievirus A24v transduction by pentavalent N-acetylneuraminic acid conjugates.
Open this publication in new window or tab >>Exploring the effect of rational scaffold hopping on the inhibition of coxsackievirus A24v transduction by pentavalent N-acetylneuraminic acid conjugates
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(English)Manuscript (preprint) (Other academic)
National Category
Organic Chemistry Biological Sciences
Research subject
Biorganic Chemistry; Biorganic Chemistry
Identifiers
urn:nbn:se:umu:diva-182325 (URN)
Available from: 2021-04-19 Created: 2021-04-19 Last updated: 2021-04-21
Hurdiss, D. L., Zocherg, G., Johansson, E., Thompson, R. F., Byrne, M. J., Mistry, N., . . . Stehle, T.Genome uncoating and its unexpected inhibition studied in a pandemic strain of Coxsackievirus A24v.
Open this publication in new window or tab >>Genome uncoating and its unexpected inhibition studied in a pandemic strain of Coxsackievirus A24v
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(English)Manuscript (preprint) (Other academic)
National Category
Biological Sciences Organic Chemistry
Identifiers
urn:nbn:se:umu:diva-182332 (URN)
Available from: 2021-04-19 Created: 2021-04-19 Last updated: 2021-04-21
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