The challenges of developing and identifying a pipeline for drug development for Aspergillus fumigatus-induced lung infections

Research Article
Open access

The challenges of developing and identifying a pipeline for drug development for Aspergillus fumigatus-induced lung infections

Yuyao Zhao 1*
  • 1 North London Collegiate School (Singapore)    
  • *corresponding author nancyzhao802@gmail.com
Published on 20 December 2023 | https://doi.org/10.54254/2753-8818/22/20230982
TNS Vol.22
ISSN (Print): 2753-8826
ISSN (Online): 2753-8818
ISBN (Print): 978-1-83558-217-6
ISBN (Online): 978-1-83558-218-3

Abstract

Aspergillosis, a lung infection brought on by Aspergillus, is particularly dangerous for people with impaired immune systems. Aspergillosis is difficult to prevent since the spores are found in the environment on a regular basis. Healthy people are usually unaffected, but those with compromised immune systems must deal with the challenges of medication resistance and reinfection throughout therapy. Additionally, Aspergillus fumigatus is listed as a fungal priority pathogen by the World Health Organization. To tackle this developing pandemic and improve outcomes for those afflicted, effective management measures and further research are required. This paper analyses the challenges faced in the drug pipeline against Aspergillus fumigatus, so as to address the spread of the disease of Aspergillosis lung infections. Recognizing these challenges could help researchers consider other possible modes of treatment and what to look out for. The paper proposes that a possibility could be a combination of various drugs, along with immunotherapy, in order to tackle the disease effectively. This means that continued research and efforts are still needed in the drug development pipeline for Aspergillus fumigatus, preferably with more funding. The threat it poses is significant, as its increased infection rate suggests it has the potential to become an epidemic in the next 50 years. Thus, a breakthrough would be significant in ensuring higher survival rates among patients.

Keywords:

aspergillus fumigatus, drug development, drug discovery pipeline, challenges of developing a drug

Zhao,Y. (2023). The challenges of developing and identifying a pipeline for drug development for Aspergillus fumigatus-induced lung infections. Theoretical and Natural Science,22,201-207.
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References

[1]. Rolle, A. M., Hasenberg, M., Thornton, C. R., et al. (2016). ImmunoPET/MR imaging allows specific detection of Aspergillus fumigatus lung infection in vivo. Proceedings of the National Academy of Sciences of the United States of America, 113, E1026-E1033.

[2]. Gerber, B., Guggenberger, R., Fasler, D., et al. (2012). Reversible skeletal disease and high fluoride serum levels in hematologic patients receiving voriconazole. Blood, 120(11), 2390-2394.

[3]. Mayr, A., & Lass-Florl, C. (2011). Epidemiology and antifungal resistance in invasive Aspergillosis according to primary disease: review of the literature. European Journal of Medical Research, 16(4), 153-157.

[4]. Perfect, J. R. (2016). Is there an emerging need for new antifungals? Expert Opinion on Emerging Drugs, 21(2), 1-3.

[5]. Roemer, T., Xu, D., Singh, S. B., et al. (2011). Confronting the challenges of natural product-based antifungal discovery. Chemistry & Biology, 18(2), 148-164.

[6]. Mak, I. W., Evaniew, N., & Ghert, M. (2014). Lost in translation: animal models and clinical trials in cancer treatment. American Journal of Translational Research, 6(2), 114-118.

[7]. Oliver, J., Law, D., Sibley, G., et al. (2016). F901318, a novel antifungal agent from the orotomide class: discovery and me.

[8]. Law, D. (2016). The efficacy of F901318, a novel antifungal drug, in an animal model of aspergillosis. Paper presented at the ICAAC-American Society for Microbiology Conference, Boston, MA.

[9]. Torrado, J. J., Espada, R., Ballesteros, M. P., et al. (2008). Amphotericin B formulations and drug targeting. Journal of Pharmaceutical Sciences, 97(6), 2405-2425.

[10]. Chandrasekar, P. H., & Ito, J. I. (2005). Amphotericin B lipid complex in the management of invasive aspergillosis in immunocompromised patients. Clinical Infectious Diseases, 40(Suppl 6), S392-S400. doi: 10.1086/429333.

[11]. Leonardelli, F., Macedo, D., Dudiuk, C., Cabeza, M. S., Gamarra, S., & Garcia-Effron, G. (2016). Aspergillus fumigatus intrinsic fluconazole resistance is due to the naturally occurring T301I substitution in Cyp51Ap. Antimicrobial Agents and Chemotherapy, 60(9), 5420-5426. doi: 10.1128/AAC.00905-16.

[12]. Edlind, T. D., Henry, K. W., Metera, K. A., & Katiyar, S. K. (2001). Aspergillus fumigatus CYP51 sequence: potential basis for fluconazole resistance. Medical Mycology, 39, 299-302. doi: 10.1080/mmy.39.3.299.302.

[13]. Lamb, D. C., Kelly, D. E., Schunck, W. H., Shyadehi, A. Z., Akhtar, M., Lowe, D. J., Baldwin, B. C., & Kelly, S. L. (1997). The mutation T315A in Candida albicans sterol 14alpha-demethylase causes reduced enzyme activity and fluconazole resistance through reduced affinity. Journal of Biological Chemistry, 272, 5682-5688.

[14]. Fisher, B. T., Robinson, P. D., Lehrnbecher, T., Steinbach, W. J., Zaoutis, T. E., Phillips, B., & Sung, L. (2018). Risk factors for invasive fungal disease in pediatric cancer and hematopoietic stem cell transplantation: a systematic review. Journal of Pediatric Infectious Diseases Society, 7(3), 191-198. doi: 10.1093/jpids/pix030.

[15]. Sartor, V. et al. (2011) Value-driven drug development—unlocking the value of your pipeline. A-vailable at: https://www.mckinsey.com/~/media/mckinsey/dotcom/client_service/pharma% 20and%20medical%20products/pmp%20new/pdfs/780416_value_driven_drug_development_unlocking_the_value_of_your_pipeline1.pdf.

Cite this article

Zhao,Y. (2023). The challenges of developing and identifying a pipeline for drug development for Aspergillus fumigatus-induced lung infections. Theoretical and Natural Science,22,201-207.

Data availability

The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.

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About volume

Volume title: Proceedings of the 3rd International Conference on Biological Engineering and Medical Science

ISBN：978-1-83558-217-6(Print) / 978-1-83558-218-3(Online)
Editor：Alan Wang
Conference website: https://www.icbiomed.org/
Conference date: 2 September 2023
Series: Theoretical and Natural Science
Volume number: Vol.22
ISSN：2753-8818(Print) / 2753-8826(Online)

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References

[1]. Rolle, A. M., Hasenberg, M., Thornton, C. R., et al. (2016). ImmunoPET/MR imaging allows specific detection of Aspergillus fumigatus lung infection in vivo. Proceedings of the National Academy of Sciences of the United States of America, 113, E1026-E1033.

[2]. Gerber, B., Guggenberger, R., Fasler, D., et al. (2012). Reversible skeletal disease and high fluoride serum levels in hematologic patients receiving voriconazole. Blood, 120(11), 2390-2394.

[3]. Mayr, A., & Lass-Florl, C. (2011). Epidemiology and antifungal resistance in invasive Aspergillosis according to primary disease: review of the literature. European Journal of Medical Research, 16(4), 153-157.

[4]. Perfect, J. R. (2016). Is there an emerging need for new antifungals? Expert Opinion on Emerging Drugs, 21(2), 1-3.

[5]. Roemer, T., Xu, D., Singh, S. B., et al. (2011). Confronting the challenges of natural product-based antifungal discovery. Chemistry & Biology, 18(2), 148-164.

[6]. Mak, I. W., Evaniew, N., & Ghert, M. (2014). Lost in translation: animal models and clinical trials in cancer treatment. American Journal of Translational Research, 6(2), 114-118.

[7]. Oliver, J., Law, D., Sibley, G., et al. (2016). F901318, a novel antifungal agent from the orotomide class: discovery and me.

[8]. Law, D. (2016). The efficacy of F901318, a novel antifungal drug, in an animal model of aspergillosis. Paper presented at the ICAAC-American Society for Microbiology Conference, Boston, MA.

[9]. Torrado, J. J., Espada, R., Ballesteros, M. P., et al. (2008). Amphotericin B formulations and drug targeting. Journal of Pharmaceutical Sciences, 97(6), 2405-2425.

[10]. Chandrasekar, P. H., & Ito, J. I. (2005). Amphotericin B lipid complex in the management of invasive aspergillosis in immunocompromised patients. Clinical Infectious Diseases, 40(Suppl 6), S392-S400. doi: 10.1086/429333.

[11]. Leonardelli, F., Macedo, D., Dudiuk, C., Cabeza, M. S., Gamarra, S., & Garcia-Effron, G. (2016). Aspergillus fumigatus intrinsic fluconazole resistance is due to the naturally occurring T301I substitution in Cyp51Ap. Antimicrobial Agents and Chemotherapy, 60(9), 5420-5426. doi: 10.1128/AAC.00905-16.

[12]. Edlind, T. D., Henry, K. W., Metera, K. A., & Katiyar, S. K. (2001). Aspergillus fumigatus CYP51 sequence: potential basis for fluconazole resistance. Medical Mycology, 39, 299-302. doi: 10.1080/mmy.39.3.299.302.

[13]. Lamb, D. C., Kelly, D. E., Schunck, W. H., Shyadehi, A. Z., Akhtar, M., Lowe, D. J., Baldwin, B. C., & Kelly, S. L. (1997). The mutation T315A in Candida albicans sterol 14alpha-demethylase causes reduced enzyme activity and fluconazole resistance through reduced affinity. Journal of Biological Chemistry, 272, 5682-5688.

[14]. Fisher, B. T., Robinson, P. D., Lehrnbecher, T., Steinbach, W. J., Zaoutis, T. E., Phillips, B., & Sung, L. (2018). Risk factors for invasive fungal disease in pediatric cancer and hematopoietic stem cell transplantation: a systematic review. Journal of Pediatric Infectious Diseases Society, 7(3), 191-198. doi: 10.1093/jpids/pix030.

[15]. Sartor, V. et al. (2011) Value-driven drug development—unlocking the value of your pipeline. A-vailable at: https://www.mckinsey.com/~/media/mckinsey/dotcom/client_service/pharma% 20and%20medical%20products/pmp%20new/pdfs/780416_value_driven_drug_development_unlocking_the_value_of_your_pipeline1.pdf.

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