Understanding the role of Ca2+ via transient receptor potential (TRP) channel in viral infection: Implications in developing future antiviral strategies

Kumar, Pawan; Radhakrishnan, Anukrishna; Mukherjee, Tathagata; Khamaru, Somlata; Chattopadhyay, Soma; Chattopadhyay, Subhasis

doi:10.1016/j.virusres.2022.198992

Cited by 6 publications

(4 citation statements)

References 115 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TRP channels in general and lyososmal Ca 2+ channels specifically have been associated with viral infections beyond the flavivirus genus (Chao et al, 2023; Grimm et al, 2017; Kumar et al, 2022; Rosato et al, 2021). We thus sought to investigate whether the TRPML2 agonist ML2-SA1 is also effective against endocytosed viruses beyond ZIKV.…”

Section: Resultsmentioning

confidence: 99%

“…Both TPCs (two-pore channels) and TRPML channels are endolysosomal cation channels which play important roles in viral infections (Chao et al, 2023; Grimm et al, 2017; Huang et al, 2021; Kumar et al, 2022; Rosato et al, 2021; Sakurai et al, 2015; Santoni et al, 2020). However, their antiviral potential is not yet fully explored, in part because specific functional modulators are missing.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Late stages of the Zika virus life cycle are impaired by a selective TRPML2 agonist

Schwickert,

Glitscher,

Bender

et al. 2024

Preprint

View full text Add to dashboard Cite

The flavivirus genus includes human pathogenic viruses such as Dengue (DENV), West Nile (WNV) and Zika virus (ZIKV) posing a global health threat due to limited treatment options. Ion channels are crucial for various viral life cycle stages, but their potential as targets for antivirals is often not fully realized due to the lack of selective modulators. Here, we observe that the human endolysosomal cation channel TRPML2 agonist ML2-SA1 impairs the late life cycle stages of ZIKV, thus underscoring TRPML2 as a promising antiviral target. Upon treatment with ML2-SA1, levels of intracellular genomes and number of released virus particles of two different ZIKV isolates were significantly reduced. ML2-SA1-treated cells displayed enlarged vesicular structures and multivesicular bodies with ZIKV envelope protein accumulation. However, no increased ZIKV degradation in lysosomal compartments was observed. Rather, the antiviral effect of ML2-SA1 seemed to manifest by the compound's negative impact on genome replication. Moreover, ML2-SA1 treatment also led to intracellular cholesterol accumulation. ZIKV as well as many other viruses including the Orthohepevirus Hepatitis E virus (HEV) rely on the endolysosomal system and are affected by intracellular cholesterol levels to complete their life cycle. Since we observed ML2-SA1 to also negatively impact HEV infections in vitro, this compound may harbor a broader antiviral potential through perturbing the intracellular cholesterol distribution. Besides underscoring the potential of TRPML2 as a promising target for combatting viral infections, we uncover a tentative connection between this protein and cholesterol distribution within the context of infectious diseases.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Late stages of the Zika virus life cycle are impaired by a selective TRPML2 agonist

Schwickert,

Glitscher,

Bender

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…In recent years, despite the increased research on PEDV in various countries, the incidence of PEDV-induced diarrhea in piglets remains high in clinical practice; therefore, the search for effective anti-PEDV drugs is still a top priority for PEDV prevention and control. Calcium ion imbalance is a hallmark of viral infection ( Kumar et al, 2022 ). Several studies have shown that different viral infections lead to an imbalance of calcium ions inside and outside the cell.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of Lactiplantibacillus plantarum regulating Ca2+ affecting the replication of PEDV in small intestinal epithelial cells

Kan,

Zhang,

Liao

et al. 2023

Front. Microbiol.

View full text Add to dashboard Cite

Porcine epidemic diarrhea virus (PEDV) mainly invades the small intestine and promotes an inflammatory response, eventually leading to severe diarrhea, vomiting, dehydration, and even death of piglets, which seriously threatens the economic development of pig farming. In recent years, researchers have found that probiotics can improve the intestinal microenvironment and reduce diarrhea. At the same time, certain probiotics have been shown to have antiviral effects; however, their mechanisms are different. Herein, we aimed to investigate the inhibitory effect of Lactiplantibacillus plantarum supernatant (LP-1S) on PEDV and its mechanism. We used IPEC-J2 cells as a model to assess the inhibitory effect of LP-1S on PEDV and to further investigate the relationship between LP-1S, Ca2+, and PEDV. The results showed that a divalent cation chelating agent (EGTA) and calcium channel inhibitors (Bepridil hydrochloride and BAPTA-acetoxymethylate) could inhibit PEDV proliferation while effectively reducing the intracellular Ca2+ concentration. Furthermore, LP-1S could reduce PEDV-induced loss of calcium channel proteins (TRPV6 and PMCA1b), alleviate intracellular Ca2+ accumulation caused by PEDV infection, and promote the balance of intra- and extracellular Ca2+ concentrations, thereby inhibiting PEDV proliferation. In summary, we found that LP-1S has potential therapeutic value against PEDV, which is realized by modulating Ca2+. This provides a potential new drug to treat PEDV infection.

show abstract

“…Host cell membranes are embedded with Ca 2+ receptors, channels, exchangers, and pumps which can be perturbed by viruses facilitating infections in various ways. For example, an increase in cytosolic Ca 2+ levels activates enzymatic processes and Ca 2+ -dependent transcription factors to promote viral pathogenesis; a decrease in Ca 2+ levels in ER and Golgi may lead to virus trafficking reduction or inhibit host-mediated anti-viral immune responses, and ER mitochondrial Ca 2+ regulates apoptosis which can serve as both an anti-viral and a viral-promoting step [55]. TRP channels regulate Ca 2+ dynamics in host cells; therefore, their expression levels are critical for viral infections.…”

Section: Discussionmentioning

confidence: 99%

Nervous Necrosis Virus Modulation of European Sea Bass (Dicentrarchus labrax, L.) Immune Genes and Transcriptome towards Establishment of Virus Carrier State

Toubanaki,

Efstathiou,

Tzortzatos

et al. 2023

IJMS

View full text Add to dashboard Cite

Viral infections of teleost fish have great environmental and economic implications in aquaculture. Nervous necrosis virus (NNV) is a pathogen affecting more than 120 different species, causing high mortality and morbidity. Herein, we studied the course of NNV experimental infection of D. labrax, focusing on survivors which indicated viral carrier state. To determine the carrier state of D. labrax head kidney, we performed a gene expression analysis of selected immune-related genes and we profiled its transcriptome 14 days post infection (dpi). All tested genes showed clear differentiations in expression levels while most of them were up-regulated 14 dpi suggesting that their role is not limited in early antiviral responses, but they are also implicated in disease persistence. To gain a better understanding of the fish that survived the acute infection but still maintained a high viral load, we studied the differential expression of 124 up-regulated and 48 down-regulated genes in D. labrax head kidney, at 14 dpi. Concluding, the NNV virus persistent profile was assessed in D. labrax, where immune-related gene modification was intense (14 dpi) and the head kidney transcriptome profile at this time point offered a glimpse into host attempts to control the infection in asymptomatic carriers.

show abstract

Understanding the role of Ca2+ via transient receptor potential (TRP) channel in viral infection: Implications in developing future antiviral strategies

Cited by 6 publications

References 115 publications

Late stages of the Zika virus life cycle are impaired by a selective TRPML2 agonist

Late stages of the Zika virus life cycle are impaired by a selective TRPML2 agonist

Mechanism of Lactiplantibacillus plantarum regulating Ca2+ affecting the replication of PEDV in small intestinal epithelial cells

Nervous Necrosis Virus Modulation of European Sea Bass (Dicentrarchus labrax, L.) Immune Genes and Transcriptome towards Establishment of Virus Carrier State

Contact Info

Product

Resources

About