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  1. Article ; Online: Cryptococcal proteases exhibit the potential to activate the latent SARS-CoV-2 spike protein

    Nozethu Mjokane / Saheed Sabiu / Olufemi S. Folorunso / Onele M.N. Gcilitshana / Jacobus Albertyn / Carolina H. Pohl / Olihile M. Sebolai

    Journal of Infection and Public Health, Vol 17, Iss 2, Pp 263-

    2024  Volume 270

    Abstract: Background: The COVID-19 pandemic has affected more than 650 million people and resulted in over 6.8 million deaths. Notably, the disease could co-manifest with microbial infections, like cryptococcosis, which also presents as a primary lung infection. ... ...

    Abstract Background: The COVID-19 pandemic has affected more than 650 million people and resulted in over 6.8 million deaths. Notably, the disease could co-manifest with microbial infections, like cryptococcosis, which also presents as a primary lung infection. Objective: In this contribution, we sought to determine if cryptococcal supernatant (which contains secreted furin-like proteases) could activate the SARS-CoV-2 spike protein. Methods: Molecular docking of the crystal structures of the SARS-CoV-2 spike protein (target) and selected cryptococcal proteases (ligands) was executed using the high ambiguity driven protein-protein docking (HADDOCK) server, with the furin protease serving as a reference ligand. The furin protease is found in human cells and typically activates the SARS-CoV-2 spike protein.Importantly, in order to provide experimental evidence for enzymatic activity, we also assessed the biochemical efficiency of cryptococcal proteases to initiate viral entry into HEK-293 T cells by SARS-CoV-2 spike pseudotyped Lentivirus. Results: We show that the selected cryptococcal proteases could interact with the spike protein, and some had a better or comparable binding affinity for the spike protein than furin protease following an in silico comparative analysis of the molecular docking parameters. Furthermore, it was noted that the biochemical efficiency of the cryptococcal supernatant to transduce HEK-293 T cells with SARS-CoV-2 pseudovirions was comparable (p > 0.05) to that of recombinant furin. Conclusions: Taken together, these data show that cryptococcal proteases could activate the SARS-CoV-2 spike protein. In practice, it may be critical to determine if patients have an underlying cryptococcal infection, as this microbe could secrete proteases that may further activate the SARS-CoV-2 viral particles, thus undermining COVID-19 intervention measures.
    Keywords Cryptococcal protease ; Furin protease ; HEK-293 T cells ; Protein-protein docking ; SARS-CoV-2 spike protein ; Infectious and parasitic diseases ; RC109-216 ; Public aspects of medicine ; RA1-1270
    Subject code 612
    Language English
    Publishing date 2024-02-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: The Repurposing of Acetylsalicylic Acid as a Photosensitiser to Inactivate the Growth of Cryptococcal Cells

    Adepemi O. Ogundeji / Nozethu Mjokane / Olufemi S. Folorunso / Carolina H. Pohl / Martin M. Nyaga / Olihile M. Sebolai

    Pharmaceuticals, Vol 14, Iss 404, p

    2021  Volume 404

    Abstract: Photodynamic treatment (PDT) is often successful when used against aerobic microbes, given their natural susceptibility to oxidative damage. To this end, the current study aimed to explore the photodynamic action of acetylsalicylic acid (ASA; aspirin, ... ...

    Abstract Photodynamic treatment (PDT) is often successful when used against aerobic microbes, given their natural susceptibility to oxidative damage. To this end, the current study aimed to explore the photodynamic action of acetylsalicylic acid (ASA; aspirin, which is commonly used to treat non-infectious ailments), when administered to respiring cryptococcal cells. The treatment of cryptococcal cells, i.e., exposure to 0.5 or 1 mM of ASA in the presence of ultraviolet light (UVL) for 10 min, resulted in a significant ( p < 0.05) reduction in the growth of tested cells when compared to non-treated (non-Rx) cells, i.e., no ASA and no UVL. The treated cells were also characterised by diseased mitochondria, which is crucial for the survival of respiring cells, as observed by a significant ( p < 0.05) loss of mitochondrial membrane potential (ΔΨM) and significant ( p < 0.05) accumulation of reactive oxygen species (ROS) when compared to non-Rx cells. Moreover, the photolytic products of acetylsalicylic acid altered the ultrastructural appearance of treated cells as well as limited the expression levels of the capsular-associated gene, CAP64, when compared to non-Rx cells. The results of the study highlight the potential use of ASA as a photosensitiser that is effective for controlling the growth of cryptococcal cells. Potentially, this treatment can also be used as an adjuvant, to complement and support the usage of current anti-microbial agents.
    Keywords acetylsalicylic acid (ASA ; aspirin) ; capsule ; CAP64 ; Cryptococcus ; membrane potential (ΔΨM) ; photodynamic treatment ; Medicine ; R ; Pharmacy and materia medica ; RS1-441
    Subject code 630
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Cryptococcal Protease(s) and the Activation of SARS-CoV-2 Spike (S) Protein

    Nozethu Mjokane / Maphori Maliehe / Olufemi S. Folorunso / Adepemi O. Ogundeji / Onele M. N. Gcilitshana / Jacobus Albertyn / Carolina H. Pohl / Olihile M. Sebolai

    Cells, Vol 11, Iss 437, p

    2022  Volume 437

    Abstract: In this contribution, we report on the possibility that cryptococcal protease(s) could activate the SARS-CoV-2 spike (S) protein. The S protein is documented to have a unique four-amino-acid sequence (underlined, S PRRA R↓S) at the interface between the ... ...

    Abstract In this contribution, we report on the possibility that cryptococcal protease(s) could activate the SARS-CoV-2 spike (S) protein. The S protein is documented to have a unique four-amino-acid sequence (underlined, S PRRA R↓S) at the interface between the S1 and S2 sites, that serves as a cleavage site for the human protease, furin. We compared the biochemical efficiency of cryptococcal protease(s) and furin to mediate the proteolytic cleavage of the S1/S2 site in a fluorogenic peptide. We show that cryptococcal protease(s) processes this site in a manner comparable to the efficiency of furin ( p > 0.581). We conclude the paper by discussing the impact of these findings in the context of a SARS-CoV-2 disease manifesting while there is an underlying cryptococcal infection.
    Keywords cryptococcal infection ; Cryptococcus ; Cryptococcus neoformans ; fluorogenic peptide ; furin ; protease ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Environmental Factors That Contribute to the Maintenance of Cryptococcus neoformans Pathogenesis

    Maphori Maliehe / Mathope A. Ntoi / Shayanki Lahiri / Olufemi S. Folorunso / Adepemi O. Ogundeji / Carolina H. Pohl / Olihile M. Sebolai

    Microorganisms, Vol 8, Iss 2, p

    2020  Volume 180

    Abstract: The ability of microorganisms to colonise and display an intracellular lifestyle within a host body increases their fitness to survive and avoid extinction. This host−pathogen association drives microbial evolution, as such organisms are under selective ... ...

    Abstract The ability of microorganisms to colonise and display an intracellular lifestyle within a host body increases their fitness to survive and avoid extinction. This host−pathogen association drives microbial evolution, as such organisms are under selective pressure and can become more pathogenic. Some of these microorganisms can quickly spread through the environment via transmission. The non-transmittable fungal pathogens, such as Cryptococcus, probably return into the environment upon decomposition of the infected host. This review analyses whether re-entry of the pathogen into the environment causes restoration of its non-pathogenic state or whether environmental factors and parameters assist them in maintaining pathogenesis. Cryptococcus (C.) neoformans is therefore used as a model organism to evaluate the impact of environmental stress factors that aid the survival and pathogenesis of C. neoformans intracellularly and extracellularly.
    Keywords cryptococcus ; environmental factors ; pathogenesis ; survival ; virulence factors ; transcriptional factors ; signalling factors ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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