The Possible Role of Microbial Proteases in Facilitating SARS-CoV-2 Brain Invasion

Mjokane, Nozethu; Folorunso, Olufemi Samuel; Ogundeji, Adepemi O.; Sebolai, Olihile M.

doi:10.3390/biology10100966

Cited by 7 publications

(6 citation statements)

References 105 publications

(113 reference statements)

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“…Both HIV and SARS-CoV-2 can activate the NLRP3 in ammasome, precipitating immune imbalances through in ammasome activation 12 . Research has indicated that the novel coronavirus may instigate a cytokine storm, targeting endothelial cells and compromising the blood-brain barrier, consequently elevating the risk of central nervous system infections 13 .…”

Section: Discussionmentioning

confidence: 99%

Neurosyphilis with Concomitant Cryptococcal Meningitis in a Patient with AIDS after COVID-19: a case report

Wang,

Pan

2024

Preprint

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Background The common infections agents causing meningitis in patients with human immunodeficiency virus (HIV) include Cryptococcus neoformans and Treponema pallidum. Furthermore, there is an elevated risk of meningitis in patients with HIV concomitantly infected with SARS-CoV-2. Case presentation: A 38-year-old male presented with headache and dizziness. After hospitalization, polymerase chain reaction test for SARS-CoV-2 in nasopharyngeal swab was positive, and lumbar puncture revealed neurosyphilis with concomitant cryptococcal meningitis. He underwent Paxlovid, penicillin, antifungal and antiretroviral treatment. The patient had no other neurological symptoms and was stable during the 6-month follow-up period. Conclusions During the COVID-19 pandemic, patients with HIV, particularly those not underwent antiretroviral therapy, are at higher risk for severe infections, including central nervous system complications, due to their compromised immune systems.

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Section: Discussionmentioning

confidence: 99%

Neurosyphilis with Concomitant Cryptococcal Meningitis in a Patient with AIDS after COVID-19: a case report

Wang,

Pan

2024

Preprint

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“…And that, any mutation to this amino acid sequence would impair furin hydrolysis. From the docking data, we established that furin protease and A. fumigatus alkaline protease 1 belong to the same family, thus would use common binding sites and have similar mechanistic features, i.e., defined by the nature of the nucleophilic amino acid in the active site [ 18 , 34 ]. Therefore, it is reasonable to foresee A. fumigatus alkaline protease 1 (serine-based) catalysing the SARS-CoV-2 spike protein similarly to furin protease.…”

Section: Discussionmentioning

confidence: 99%

Aspergillus fumigatus secretes a protease(s) that displays in silico binding affinity towards the SARS-CoV-2 spike protein and mediates SARS-CoV-2 pseudovirion entry into HEK-293T cells

Mjokane,

Akintemi,

Sabiu

et al. 2024

Virol J

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Background The novel coronavirus disease of 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Data from the COVID-19 clinical control case studies showed that this disease could also manifest in patients with underlying microbial infections such as aspergillosis. The current study aimed to determine if the Aspergillus (A.) fumigatus culture media (i.e., supernatant) possessed protease activity that was sufficient to activate the SARS-CoV-2 spike protein. Methods The supernatant was first analysed for protease activity. Thereafter, it was assessed to determine if it possessed proteolytic activity to cleave a fluorogenic mimetic peptide of the SARS-CoV-2 spike protein that contained the S1/S2 site and a full-length spike protein contained in a SARS-CoV-2 pseudovirion. To complement this, a computer-based tool, HADDOCK, was used to predict if A. fumigatus alkaline protease 1 could bind to the SARS-CoV-2 spike protein. Results We show that the supernatant possessed proteolytic activity, and analyses of the molecular docking parameters revealed that A. fumigatus alkaline protease 1 could bind to the spike protein. To confirm the in silico data, it was imperative to provide experimental evidence for enzymatic activity. Here, it was noted that the A. fumigatus supernatant cleaved the mimetic peptide as well as transduced the HEK-293T cells with SARS-CoV-2 pseudovirions. Conclusion These results suggest that A. fumigatus secretes a protease(s) that activates the SARS-CoV-2 spike protein. Importantly, should these two infectious agents co-occur, there is the potential for A. fumigatus to activate the SARS-CoV-2 spike protein, thus aggravating COVID-19 development.

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“…For Cryptococcus neoformans —an encapsulated fungus responsible for pneumonia and meningitis in immunocompromised individuals—the activity of serine protease, as well as secreted metalloprotease Mpr1, was demonstrated as being pivotal for interactions with microvascular endothelial cells and the disruption of the blood–brain barrier, facilitating subsequent fungal traversal to the central nervous system [ 42 , 43 ]. Moreover, Mjokane et al [ 44 , 45 ] speculated recently that the activity of uncharacterized serine protease from C. neoformans may activate the SARS-CoV-2 spike (S) protein, with consequent membrane fusion and the endocytosis of virial particles by host cells, thus facilitating the development of the coronavirus disease COVID-19 in patients affected with concomitant fungal infection [ 44 , 45 ].…”

Section: Involvement In Binding Adhesion Self-aggregation and Biofilm...mentioning

confidence: 99%

More than Just Protein Degradation: The Regulatory Roles and Moonlighting Functions of Extracellular Proteases Produced by Fungi Pathogenic for Humans

Satała

Bras

Kozik

et al. 2023

JoF

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Extracellular proteases belong to the main virulence factors of pathogenic fungi. Their proteolytic activities plays a crucial role in the acquisition of nutrients from the external environment, destroying host barriers and defenses, and disrupting homeostasis in the human body, e.g., by affecting the functions of plasma proteolytic cascades, and playing sophisticated regulatory roles in various processes. Interestingly, some proteases belong to the group of moonlighting proteins, i.e., they have additional functions that contribute to successful host colonization and infection development, but they are not directly related to proteolysis. In this review, we describe examples of such multitasking of extracellular proteases that have been reported for medically important pathogenic fungi of the Candida, Aspergillus, Penicillium, Cryptococcus, Rhizopus, and Pneumocystis genera, as well as dermatophytes and selected endemic species. Additional functions of proteinases include supporting binding to host proteins, and adhesion to host cells. They also mediate self-aggregation and biofilm formation. In addition, fungal proteases affect the host immune cells and allergenicity, understood as the ability to stimulate a non-standard immune response. Finally, they play a role in the proper maintenance of cellular homeostasis. Knowledge about the multifunctionality of proteases, in addition to their canonical roles, greatly contributes to an understanding of the mechanisms of fungal pathogenicity.

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The Possible Role of Microbial Proteases in Facilitating SARS-CoV-2 Brain Invasion

Cited by 7 publications

References 105 publications

Neurosyphilis with Concomitant Cryptococcal Meningitis in a Patient with AIDS after COVID-19: a case report

Neurosyphilis with Concomitant Cryptococcal Meningitis in a Patient with AIDS after COVID-19: a case report

Aspergillus fumigatus secretes a protease(s) that displays in silico binding affinity towards the SARS-CoV-2 spike protein and mediates SARS-CoV-2 pseudovirion entry into HEK-293T cells

More than Just Protein Degradation: The Regulatory Roles and Moonlighting Functions of Extracellular Proteases Produced by Fungi Pathogenic for Humans

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