The immunomodulatory effects of barettin and involvement of the kinases CAMK1α and RIPK2

Lind, Karianne F.; Østerud, Bjarne; Hansen, Espen; Jørgensen, Trond Ø.; Andersen, Jeanette Hammer

doi:10.3109/08923973.2015.1082584

Cited by 10 publications

(11 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are few inhibitors of CAMK1 that have been identified to date (such as Barettin 72 or pyridine amides 73 ), which have a role in inflammation targeting IL-10. 72 Previous in vitro work has shown that inhibiting CAMK1 in cells reduces IL-10, the master anti-inflammatory interleukin. 74 In the present study, there is no significant difference in the IL-10 levels between the untreated and pyronaridine-treated infected groups so it seems unlikely that CAMK1 inhibition would be involved in the mechanism of action of inhibition of SAR-CoV-2.…”

Section: Resultsmentioning

confidence: 99%

Pyronaridine Protects against SARS-CoV-2 Infection in Mouse

et al. 2022

View full text Add to dashboard Cite

There are currently relatively few small-molecule antiviral drugs that are either approved or emergency-approved for use against severe acute respiratory coronavirus 2 (SARS-CoV-2). One of these is remdesivir, which was originally repurposed from its use against Ebola. We evaluated three molecules we had previously identified computationally with antiviral activity against Ebola and Marburg and identified pyronaridine, which inhibited the SARS-CoV-2 replication in A549-ACE2 cells. The in vivo efficacy of pyronaridine has now been assessed in a K18-hACE transgenic mouse model of COVID-19. Pyronaridine treatment demonstrated a statistically significant reduction of viral load in the lungs of SARS-CoV-2-infected mice, reducing lung pathology, which was also associated with significant reduction in the levels of pro-inflammatory cytokines/chemokine and cell infiltration. Pyronaridine inhibited the viral PL pro activity in vitro (IC 50 of 1.8 μM) without any effect on M pro , indicating a possible molecular mechanism involved in its ability to inhibit SARS-CoV-2 replication. We have also generated several pyronaridine analogs to assist in understanding the structure activity relationship for PL pro inhibition. Our results indicate that pyronaridine is a potential therapeutic candidate for COVID-19.

show abstract

Section: Resultsmentioning

confidence: 99%

Pyronaridine Protects against SARS-CoV-2 Infection in Mouse

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Furthermore, we have shown that pyronaridine may target Pl pro as well as CAMK1. There are few inhibitors of CAMK1 that have been identified to date (such as Barettin (62) or pyridine amides (63)) which has a role in inflammation targeting IL-10 (62). Previous in vitro work has shown that inhibiting CAMK1 in cells reduces IL-10, the master anti-inflammatory interleukin (64).…”

Section: Discussionmentioning

confidence: 99%

Pyronaridine Protects Against SARS-CoV-2 in Mouse

Puhl

Gomes

Damasceno

et al. 2021

Preprint

View full text Add to dashboard Cite

There are currently relatively few small-molecule antiviral drugs that are either approved or emergency approved for use against SARS-CoV-2. One of these is remdesivir, which was originally repurposed from its use against Ebola and functions by causing early RNA chain termination. We used this as justification to evaluate three molecules we had previously identified computationally with antiviral activity against Ebola and Marburg. Out of these we previously identified pyronaridine, which inhibited the SARS-CoV-2 replication in A549-ACE2 cells. Herein, the in vivo efficacy of pyronaridine has now been assessed in a K18-hACE transgenic mouse model of COVID-19. Pyronaridine treatment demonstrated a statistically significant reduction of viral load in the lungs of SARS CoV-2 infected mice. Furthermore, the pyronaridine treated group reduced lung pathology, which was also associated with significant reduction in the levels of pro-inflammatory cytokines/chemokine and cell infiltration. Notably, pyronaridine inhibited the viral PLpro activity in vitro (IC50 of 1.8 uM) without any effect on Mpro, indicating a possible molecular mechanism involved in its ability to inhibit SARS-CoV-2 replication. Interestingly, pyronaridine also selectively inhibits the host kinase CAMK1 (IC50 of 2.4 uM). We have also generated several pyronaridine analogs to assist in understanding the structure activity relationship for PLpro inhibition. Our results indicate that pyronaridine is a potential therapeutic candidate for COVID-19.

show abstract

“…In 2015, Karianne F. Lind et al reported that barettin ( 70 , Figure 20), which was first isolated and described in 1986 [90], inhibited RIPK2 (IC 50 = 8.0 μM), CAMK1a (IC 50 = 5.7 μM), SIK2 (IC 50 = 6.1 μM) and produced anti-inflammatory effects in vitro [91,92]. In 2015, Rebecca Horbert et al reported the synthetic compound 71 (Figure 20) with a 3,5-diarylpyrazin-2-one core that was based on hamacanthins A and B, which are sponge natural products of the bis-indole alkaloid class [93].…”

Section: Discussionmentioning

confidence: 99%

A Systematic Review of Recently Reported Marine Derived Natural Product Kinase Inhibitors

Wang

Zhang

et al. 2019

Marine Drugs

View full text Add to dashboard Cite

Protein kinases are validated drug targets for a number of therapeutic areas, as kinase deregulation is known to play an essential role in many disease states. Many investigated protein kinase inhibitors are natural product small molecules or their derivatives. Many marine-derived natural products from various marine sources, such as bacteria and cyanobacteria, fungi, animals, algae, soft corals, sponges, etc. have been found to have potent kinase inhibitory activity, or desirable pharmacophores for further development. This review covers the new compounds reported from the beginning of 2014 through the middle of 2019 as having been isolated from marine organisms and having potential therapeutic applications due to kinase inhibitory and associated bioactivities. Moreover, some existing clinical drugs based on marine-derived natural product scaffolds are also discussed.

show abstract

The immunomodulatory effects of barettin and involvement of the kinases CAMK1α and RIPK2

Abstract: The anti-inflammatory activity of barettin is exerted through the regulation of inflammatory mediators such as MCP-1 and IL-10, possibly via inhibition of kinases.

Cited by 10 publications

References 45 publications

Pyronaridine Protects against SARS-CoV-2 Infection in Mouse

Pyronaridine Protects against SARS-CoV-2 Infection in Mouse

Pyronaridine Protects Against SARS-CoV-2 in Mouse

A Systematic Review of Recently Reported Marine Derived Natural Product Kinase Inhibitors

Contact Info

Product

Resources

About