Theoretical and Natural Science
- The Open Access Proceedings Series for Conferences
Series Vol. 6 , 03 August 2023
* Author to whom correspondence should be addressed.
The coronavirus SARS-CoV-2 is currently spreading throughout the world. The severity of the situation has increased efforts to create efficient prevention and treatment strategies. SARS-CoV-2 has been the subject of numerous experiments, and as a result, scientists now understand it better. Usually, the virus exits the cell through exocytosis. However, SARS-CoV-2 utilizes deacidified lysosomes as a means to egress from the infected cell.This proposal shows a deep understanding of lysosomal viral secretion and elaborates on the impact of the lysosomal proton pump, which functions to regulate the pH value of the endo-lysosomal environment, on lysosome functioning. Experiment are proposed to test the ability of a lysosomal proton pump inhibitor to impede the egress of the SARS-CoV-2 virus and analyze its potential application in a therapeutic target.
SARS-CoV-2. deacidified lysosomes, lysosomal viral secretion, lysosomal proton pump
1. Pal, M., Berhanu, G., Desalegn, C., & Kandi, V. (2020). Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2): An Update. Cureus. https://doi.org/10.7759/cureus.7423
2. Li, H., Zhou, Y., Zhang, M., Wang, H., Zhao, Q., & Liu, J. (2020). Updated Approaches against SARS-CoV-2. Antimicrobial Agents and Chemotherapy, 64(6). https://doi.org/10.1128/aac.00483-20
3. Singh, D., & Yi, S. V. (2021). On the origin and evolution of SARS-CoV-2. Experimental & Molecular Medicine, 53(4), 537–547. https://doi.org/10.1038/s12276-021-00604-z
4. V’kovski, P., Kratzel, A., Steiner, S., Stalder, H., & Thiel, V. (2020). Coronavirus biology and replication: implications for SARS-CoV-2. Nature Reviews Microbiology, 19(3), 155–170. https://doi.org/10.1038/s41579-020-00468-6
5. Du, L., He, Y., Zhou, Y., Liu, S., Zheng, B. J., & Jiang, S. (2009). The spike protein of SARS-CoV — a target for vaccine and therapeutic development. Nature Reviews Microbiology, 7(3), 226–236. https://doi.org/10.1038/nrmicro2090
6. Xia, X. (2021). Domains and Functions of Spike Protein in SARS-Cov-2 in the Context of Vaccine Design. Viruses, 13(1), 109. https://doi.org/10.3390/v13010109
7. Bamford, C. (2020, December 22). New coronavirus variant: what is the spike protein and why are mutations on it important? The Conversation. https://theconversation.com/new-coronavirus-variant-what-is-the-spike-protein-and-why-are-mutations-on-it-important-152463
8. Blaess, M., Kaiser, L., Sauer, M., Csuk, R., & Deigner, H. P. (2020). COVID-19/SARS-CoV-2 Infection: Lysosomes and Lysosomotropism Implicate New Treatment Strategies and Personal Risks. International Journal of Molecular Sciences, 21(14), 4953. https://doi.org/10.3390/ijms21144953
9. Scialo, F., Daniele, A., Amato, F., Pastore, L., Matera, M. G., Cazzola, M., Castaldo, G., & Bianco, A. (2020). ACE2: The Major Cell Entry Receptor for SARS-CoV-2. Lung, 198(6), 867–877. https://doi.org/10.1007/s00408-020-00408-4
10. Jackson, C. B., Farzan, M., Chen, B., & Choe, H. (2021). Mechanisms of SARS-CoV-2 entry into cells. Nature Reviews Molecular Cell Biology, 23(1), 3–20. https://doi.org/10.1038/s41580-021-00418-x
11. Wong, N. A., & Saier, M. H. (2021). The SARS-Coronavirus Infection Cycle: A Survey of Viral Membrane Proteins, Their Functional Interactions and Pathogenesis. International Journal of Molecular Sciences, 22(3), 1308. https://doi.org/10.3390/ijms22031308
12. Chen, D., Zheng, Q., Sun, L., Ji, M., Li, Y., Deng, H., & Zhang, H. (2021). ORF3a of SARS-CoV-2 promotes lysosomal exocytosis-mediated viral egress. Developmental Cell, 56(23), 3250–3263.e5. https://doi.org/10.1016/j.devcel.2021.10.006
13. Bhat, O. M., & Li, P.-L. (2021). Lysosome Function in Cardiovascular Diseases. Cellular Physiology and Biochemistry, 55(3), 277–300. https://doi.org/10.33594/000000373
14. Ghosh, S., Dellibovi-Ragheb, T. A., Kerviel, A., Pak, E., Qiu, Q., Fisher, M., Takvorian, P. M., Bleck, C., Hsu, V. W., Fehr, A. R., Perlman, S., Achar, S. R., Straus, M. R., Whittaker, G. R., de Haan, C. A., Kehrl, J., Altan-Bonnet, G., & Altan-Bonnet, N. (2020). β-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic Secretory Pathway. Cell, 183(6), 1520–1535.e14. https://doi.org/10.1016/j.cell.2020.10.039
15. Taştemur, E., & Ataseven, H. (2020). Is it possible to use Proton Pump Inhibitors in COVID-19 treatment and prophylaxis? Medical Hypotheses, 143, 110018. https://doi.org/10.1016/j.mehy.2020.110018
16. Cipriano, D. J., Wang, Y., Bond, S., Hinton, A., Jefferies, K. C., Qi, J., & Forgac, M. (2008). Structure and regulation of the vacuolar ATPases. Biochimica et Biophysica Acta (BBA) - Bioenergetics, 1777(7–8), 599–604. https://doi.org/10.1016/j.bbabio.2008.03.013
17. Wang, X., Melino, G., & Shi, Y. (2021). Actively or passively deacidified lysosomes push β-coronavirus egress. Cell Death & Disease, 12(3). https://doi.org/10.1038/s41419-021-03501-5
18. FUTAI, M., SUN-WADA, G. H., WADA, Y., MATSUMOTO, N., & NAKANISHI-MATSUI, M. (2019). Vacuolar-type ATPase: A proton pump to lysosomal trafficking. Proceedings of the Japan Academy, Series B, 95(6), 261–277. https://doi.org/10.2183/pjab.95.018
19. Stransky, L., Cotter, K., & Forgac, M. (2016). The Function of V-ATPases in Cancer. Physiological Reviews, 96(3), 1071–1091. https://doi.org/10.1152/physrev.00035.2015
20. Abbas, Y. M., Wu, D., Bueler, S. A., Robinson, C. V., & Rubinstein, J. L. (2020). Structure of V-ATPase from the mammalian brain. Science, 367(6483), 1240–1246. https://doi.org/10.1126/science.aaz2924
21. Wang, Q., Zhang, Y., Wu, L., Niu, S., Song, C., Zhang, Z., Lu, G., Qiao, C., Hu, Y., Yuen, K. Y., Wang, Q., Zhou, H., Yan, J., & Qi, J. (2020). Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2. Cell, 181(4), 894–904.e9. https://doi.org/10.1016/j.cell.2020.03.045
22. Zhang, H., & Zhang, H. (2021). Entry, egress and vertical transmission of SARS-CoV-2. Journal of Molecular Cell Biology. https://doi.org/10.1093/jmcb/mjab013
23. Yang, B., Jia, Y., Meng, Y., Xue, Y., Liu, K., Li, Y., Liu, S., Li, X., Cui, K., Shang, L., Cheng, T., Zhang, Z., Hou, Y., Yang, X., Yan, H., Duan, L., Tong, Z., Wu, C., Liu, Z., . . . Shang, G. (2022). SNX27 suppresses SARS-CoV-2 infection by inhibiting viral lysosome/late endosome entry. Proceedings of the National Academy of Sciences, 119(4). https://doi.org/10.1073/pnas.2117576119
24. Daidoji, T., Kajikawa, J., Arai, Y., Watanabe, Y., Hirose, R., & Nakaya, T. (2020). Infection of Human Tracheal Epithelial Cells by H5 Avian Influenza Virus Is Regulated by the Acid Stability of Hemagglutinin and the pH of Target Cell Endosomes. Viruses, 12(1), 82. https://doi.org/10.3390/v12010082
The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License. Authors who publish this series agree to the following terms:
1. Authors retain copyright and grant the series right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this series.
2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the series's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this series.
3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See Open Access Instruction).