Potential Antiviral Strategy Exploiting Dependence of SARS-CoV-2 Replication on Lysosome-Based Pathway

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Jun 10

PMID 35682877

Authors

Yungang Lan

Wenqi He

Gaili Wang

Zhenzhen Wang

Yuzhu Chen

Feng Gao

Deguang Song

Affiliations

Soon will be listed here.

Abstract

The recent novel coronavirus (SARS-CoV-2) disease (COVID-19) outbreak created a severe public health burden worldwide. Unfortunately, the SARS-CoV-2 variant is still spreading at an unprecedented speed in many countries and regions. There is still a lack of effective treatment for moderate and severe COVID-19 patients, due to a lack of understanding of the SARS-CoV-2 life cycle. Lysosomes, which act as "garbage disposals" for nearly all types of eukaryotic cells, were shown in numerous studies to support SARS-CoV-2 replication. Lysosome-associated pathways are required for virus entry and exit during replication. In this review, we summarize experimental evidence demonstrating a correlation between lysosomal function and SARS-CoV-2 replication, and the development of lysosomal perturbation drugs as anti-SARS-CoV-2 agents.

Citing Articles

SARS-CoV-2 Is an Electricity-Driven Virus.

McCaig C Rev Physiol Biochem Pharmacol. 2025; 187():361-410.

PMID: 39838019 DOI: 10.1007/978-3-031-68827-0_18.

The inactivation of the Niemann Pick C1 cholesterol transporter restricts SARS-CoV-2 entry into host cells by decreasing ACE2 abundance at the plasma membrane.

La Rosa P, Tiberi J, Palermo E, Stefanelli R, Tiano S, Canterini S Cell Biosci. 2024; 14(1):148.

PMID: 39707537 PMC: 11662611. DOI: 10.1186/s13578-024-01331-4.

Pathophysiology of COVID-19-Related Extrapyramidal Disorders.

Cavallieri F, Zedde M, Fioravanti V, Grisanti S, Napoli M, Moratti C Adv Exp Med Biol. 2024; 1457:111-123.

PMID: 39283423 DOI: 10.1007/978-3-031-61939-7_6.

Antagonism of epidermal growth factor receptor signaling favors hepatitis E virus life cycle.

Woytinek K, Glitscher M, Hildt E J Virol. 2024; 98(7):e0058024.

PMID: 38856640 PMC: 11265270. DOI: 10.1128/jvi.00580-24.

pH-dependent endocytosis mechanisms for influenza A and SARS-coronavirus.

Aganovic A Front Microbiol. 2023; 14:1190463.

PMID: 37234537 PMC: 10206014. DOI: 10.3389/fmicb.2023.1190463.

References

Saghir S, AlGabri N, Alagawany M, Attia Y, Alyileili S, Elnesr S . Chloroquine and Hydroxychloroquine for the Prevention and Treatment of COVID-19: A Fiction, Hope or Hype? An Updated Review. Ther Clin Risk Manag. 2021; 17:371-387. PMC: 8092643. DOI: 10.2147/TCRM.S301817. View

Alesi N, Akl E, Khabibullin D, Liu H, Nidhiry A, Garner E . TSC2 regulates lysosome biogenesis via a non-canonical RAGC and TFEB-dependent mechanism. Nat Commun. 2021; 12(1):4245. PMC: 8275687. DOI: 10.1038/s41467-021-24499-6. View

Paules C, Marston H, Fauci A . Coronavirus Infections-More Than Just the Common Cold. JAMA. 2020; 323(8):707-708. DOI: 10.1001/jama.2020.0757. View

Savini M, Zhao Q, Wang M . Lysosomes: Signaling Hubs for Metabolic Sensing and Longevity. Trends Cell Biol. 2019; 29(11):876-887. PMC: 7135937. DOI: 10.1016/j.tcb.2019.08.008. View

de Duve C . The lysosome turns fifty. Nat Cell Biol. 2005; 7(9):847-9. DOI: 10.1038/ncb0905-847. View

Forrester S, Kikuchi D, Hernandes M, Xu Q, Griendling K . Reactive Oxygen Species in Metabolic and Inflammatory Signaling. Circ Res. 2018; 122(6):877-902. PMC: 5926825. DOI: 10.1161/CIRCRESAHA.117.311401. View

Chen Y, Li M, Lu G, Shen H, Zhou J . Hydroxychloroquine/Chloroquine as Therapeutics for COVID-19: Truth under the Mystery. Int J Biol Sci. 2021; 17(6):1538-1546. PMC: 8071775. DOI: 10.7150/ijbs.59547. View

Ballabio A, Bonifacino J . Lysosomes as dynamic regulators of cell and organismal homeostasis. Nat Rev Mol Cell Biol. 2019; 21(2):101-118. DOI: 10.1038/s41580-019-0185-4. View

Meneses Calderon J, Figueroa Flores M, Paniagua Coria L, Briones Garduno J, Meneses Figueroa J, Vargas Contretas M . Nitazoxanide against COVID-19 in three explorative scenarios. J Infect Dev Ctries. 2020; 14(9):982-986. DOI: 10.3855/jidc.13274. View

10.

Reczek D, Schwake M, Schroder J, Hughes H, Blanz J, Jin X . LIMP-2 is a receptor for lysosomal mannose-6-phosphate-independent targeting of beta-glucocerebrosidase. Cell. 2007; 131(4):770-83. DOI: 10.1016/j.cell.2007.10.018. View

11.

Braulke T, Bonifacino J . Sorting of lysosomal proteins. Biochim Biophys Acta. 2008; 1793(4):605-14. DOI: 10.1016/j.bbamcr.2008.10.016. View

12.

Scott C, Vacca F, Gruenberg J . Endosome maturation, transport and functions. Semin Cell Dev Biol. 2014; 31:2-10. DOI: 10.1016/j.semcdb.2014.03.034. View

13.

Wang S, Du Q, Zhao K, Li A, Wei D, Chou K . Virtual screening for finding natural inhibitor against cathepsin-L for SARS therapy. Amino Acids. 2006; 33(1):129-35. PMC: 7087620. DOI: 10.1007/s00726-006-0403-1. View

14.

Ghosh S, Dellibovi-Ragheb T, Kerviel A, Pak E, Qiu Q, Fisher M . β-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic Secretory Pathway. Cell. 2020; 183(6):1520-1535.e14. PMC: 7590812. DOI: 10.1016/j.cell.2020.10.039. View

15.

Lu R, Zhao X, Li J, Niu P, Yang B, Wu H . Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020; 395(10224):565-574. PMC: 7159086. DOI: 10.1016/S0140-6736(20)30251-8. View

16.

Blaess M, Kaiser L, Sommerfeld O, Rentschler S, Csuk R, Deigner H . Rational Drug Repurposing: Focus on Lysosomotropism, Targets in Disease Process, Drug Profile, and Pulmonary Tissue Accumulation in SARS-CoV-2 Infection/COVID-19. Front Pharmacol. 2021; 11:584881. PMC: 7938238. DOI: 10.3389/fphar.2020.584881. View

17.

HART P, Young M . Ammonium chloride, an inhibitor of phagosome-lysosome fusion in macrophages, concurrently induces phagosome-endosome fusion, and opens a novel pathway: studies of a pathogenic mycobacterium and a nonpathogenic yeast. J Exp Med. 1991; 174(4):881-9. PMC: 2118961. DOI: 10.1084/jem.174.4.881. View

18.

Gomes C, Fernandes D, Casimiro F, da Mata G, Passos M, Varela P . Cathepsin L in COVID-19: From Pharmacological Evidences to Genetics. Front Cell Infect Microbiol. 2020; 10:589505. PMC: 7753008. DOI: 10.3389/fcimb.2020.589505. View

19.

Dabydeen S, Meneses P . The role of NH4Cl and cysteine proteases in Human Papillomavirus type 16 infection. Virol J. 2009; 6:109. PMC: 2718874. DOI: 10.1186/1743-422X-6-109. View

20.

Fujishima A, Imai Y, Nomura T, Fujisawa Y, Yamamoto Y, Sugawara T . The crystal structure of human cathepsin L complexed with E-64. FEBS Lett. 1997; 407(1):47-50. DOI: 10.1016/s0014-5793(97)00216-0. View