Verapamil has Antiviral Activities that Target Different Steps of the Influenza Virus Replication Cycle

Alam, Mohammad; Mostafa, Ahmed; Kanrai, Pumaree; Müller, Christin; Dzieciolowski, Julia; Lenz, Eva; Kuznetsova, Irina; Schult-Dietrich, Patricia; Ziebuhr, John; Dietrich, Ursula; Pleschka, Stephan

doi:10.4172/jaa.1000147

Cited by 4 publications

(4 citation statements)

References 35 publications

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“…Manipulating the intracellular Ca 2+ levels or Ca 2+ signals has been shown to inhibit the virus infection [18][19][20]23,25]. The cytosolic Ca 2+ levels or related signalling are essential to cell viability; blockade of extracellular Ca 2+ influx or release of Ca 2+ from the ER or mitochondria is detrimental to cells.…”

Section: Discussionmentioning

confidence: 99%

“…The Ca 2+ signalling participates in many steps of the virus infection cycle, e.g., entry, replication, packing and egress. Manipulation of Ca 2+ signalling by small chemicals provides a therapeutic option to control virus infection [17–25]. Here, we performed structure‐based drug screening and identified several cADPR analogues, such as C346 , based on the simulated cADPR–GAPDH complex structure.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of a small chemical as a lysosomal calcium mobilizer and characterization of its ability to inhibit autophagy and viral infection

Zhang,

Huang,

Cai

et al. 2023

The FEBS Journal

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We previously identified GAPDH as one of the cyclic adenosine diphosphoribose (cADPR)'s binding proteins and found that GAPDH participates in cADPR‐mediated Ca2+ release from ER via ryanodine receptors (RyRs). Here we aimed to chemically synthesize and pharmacologically characterize novel cADPR analogues. Based on the simulated cADPR‐GAPDH complex structure, we performed the structure‐based drug screening, identified several small chemicals with high docking scores to cADPR's binding pocket in GAPDH, and showed that two of these compounds, C244 and C346, are potential cADPR antagonists. We further synthesized several analogs of C346, and found that its analog, G42, also mobilized Ca2+ release from lysosomes. G42 alkalized lysosomal pH, and inhibited autophagosome‐lysosome fusion. Moreover, G42 markedly inhibited Zika virus (ZIKV, a flavivirus) or murine hepatitis virus (MHV, a β‐coronavirus) infections of host cells. These results suggest that G42 inhibits virus infection, likely by triggering lysosomal Ca2+ mobilization and inhibiting autophagy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of a small chemical as a lysosomal calcium mobilizer and characterization of its ability to inhibit autophagy and viral infection

Zhang,

Huang,

Cai

et al. 2023

The FEBS Journal

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“…In addition, according to previous studies, verapamil has an inhibitory effect on other viral infections such as CMV, mouse mammary tumor virus, human rhinovirus 2, Sindebis, vesicular stomatitis virus (VZV), measles and vaccinia viruses [ 43 ].…”

Section: Ccb Drugs Against Viral Infectionsmentioning

confidence: 99%

Targeting Host Calcium Channels and Viroporins: A Promising Strategy for SARS-CoV-2 Therapy

Fani,

Moossavi,

Bakhshi

et al. 2023

Future Virol.

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Despite passing the pandemic phase of the COVID-19, researchers are still investigating various drugs. Previous evidence suggests that blocking the calcium channels may be a suitable treatment option. Ca2+ is required to enhance the fusion process of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Also, some important inflammatory factors during SARS-CoV-2 infection are dependent on Ca2+ level. On the other hand, viroporins have emerged as attractive targets for antiviral therapy due to their essential role in viral replication and pathogenesis. By inhibiting the host calcium channels and viroporins, it is possible to limit the spread of infection. Therefore, calcium channel blockers (CCBs) and drugs targeting Viroporins can be considered an effective option in the fight against SARS-CoV-2.

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Cardiovascular medications and its relations with COVID-19 survival

Butt,

Eltalib,

Alim

et al. 2024

COVID-19’s Consequences on the Cardiovascular System

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Verapamil has Antiviral Activities that Target Different Steps of the Influenza Virus Replication Cycle

Cited by 4 publications

References 35 publications

Identification of a small chemical as a lysosomal calcium mobilizer and characterization of its ability to inhibit autophagy and viral infection

Identification of a small chemical as a lysosomal calcium mobilizer and characterization of its ability to inhibit autophagy and viral infection

Targeting Host Calcium Channels and Viroporins: A Promising Strategy for SARS-CoV-2 Therapy

Cardiovascular medications and its relations with COVID-19 survival

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