Evaluation of Antiviral Activity of Cyclic Ketones against Mayaro Virus

Fernandes, Luciana Sarmento; Silva, Milene L. da; Dias, Roberto Sousa; Lucindo, Marcel S. da S.; Silva, Ítalo E. P. da; Silva, Cynthia C.; Teixeira, Róbson Ricardo; Paula, Sérgio Oliveira de

doi:10.3390/v13112123

Cited by 6 publications

(4 citation statements)

References 36 publications

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“…This method of exposure of the virus and cells to polyphenols was used to study the ability of the compounds to prevent the penetration of virus to cells. Here, we investigated the ability of polyphenols 1-14 to directly interact with the viral particles (HSV-1 was pretreated with the studied compounds) [25][26][27].…”

Section: Virucidal Activity Of Polyphenolic Compounds From M Amurensi...mentioning

confidence: 99%

Polyphenols from Maackia amurensis Heartwood Protect Neuronal Cells from Oxidative Stress and Prevent Herpetic Infection

Tarbeeva,

Pislyagin,

Menchinskaya

et al. 2024

IJMS

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Here, we continued the investigation of anti-HSV-1 activity and neuroprotective potential of 14 polyphenolic compounds isolated from Maackia amurensis heartwood. We determined the absolute configurations of asymmetric centers in scirpusin A (13) and maackiazin (10) as 7R,8R and 1″S,2″S, respectively. We showed that dimeric stilbens maackin (9) and scirpusin A (13) possessed the highest anti-HSV-1 activity among polyphenols 1–14. We also studied the effect of polyphenols 9 and 13 on the early stages of HSV-1 infection. Direct interaction with the virus (virucidal activity) was the main mechanism of the antiviral activity of these compounds. The neuroprotective potential of polyphenolic compounds from M. amurensis was studied using models of 6-hydroxydopamine (6-OHDA)-and paraquat (PQ)-induced neurotoxicity. A dimeric stilbene scirpusin A (13) and a flavonoid liquiritigenin (6) were shown to be the most active compounds among the tested polyphenols. These compounds significantly increased the viability of 6-OHDA-and PQ-treated Neuro-2a cells, elevated mitochondrial membrane potential and reduced the intracellular ROS level. We also found that scirpusin A (13), liquiritigenin (6) and retusin (3) considerably increased the percentage of live Neuro-2a cells and decreased the number of early apoptotic cells. Scirpusin A (13) was the most promising compound possessing both anti-HSV-1 activity and neuroprotective potential.

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Section: Virucidal Activity Of Polyphenolic Compounds From M Amurensi...mentioning

confidence: 99%

Polyphenols from Maackia amurensis Heartwood Protect Neuronal Cells from Oxidative Stress and Prevent Herpetic Infection

Tarbeeva,

Pislyagin,

Menchinskaya

et al. 2024

IJMS

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“…A plaque-forming assay was performed, and among the 8 compounds, the Xanthenodione 9-(5-(4-chlorophenyl]furan-2-yl)-3,6-dimethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2))-dione inhibited the MAYV with EC 50 of 21.5 µM and SI of 15.8. The authors also performed a time-of-drug addition assay and found that the compound inhibits viral replication in the prior and post-treatment assays (Fernandes et al 2021 ).…”

Section: Synthetic and Semi-synthetic Inhibitors Of Mayv Replicative ...mentioning

confidence: 99%

An update on the development of antiviral against Mayaro virus: from molecules to potential viral targets

et al. 2023

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Mayaro virus (MAYV), first isolated in 1954 in Trinidad and Tobago islands, is the causative agent of Mayaro fever, a disease characterized by fever, rashes, headaches, myalgia, and arthralgia. The infection can progress to a chronic condition in over 50% of cases, with persistent arthralgia, which can lead to the disability of the infected individuals. MAYV is mainly transmitted through the bite of the female Haemagogus spp. mosquito genus. However, studies demonstrate that Aedes aegypti is also a vector, contributing to the spread of MAYV beyond endemic areas, given the vast geographical distribution of the mosquito. Besides, the similarity of antigenic sites with other Alphavirus complicates the diagnoses of MAYV, contributing to underreporting of the disease. Nowadays, there are no antiviral drugs available to treat infected patients, being the clinical management based on analgesics and non-steroidal anti-inflammatory drugs. In this context, this review aims to summarize compounds that have demonstrated antiviral activity against MAYV in vitro, as well as discuss the potentiality of viral proteins as targets for the development of antiviral drugs against MAYV. Finally, through rationalization of the data presented herein, we wish to encourage further research encompassing these compounds as potential anti-MAYV drug candidates. Supplementary Information The online version contains supplementary material available at 10.1007/s00203-023-03441-y.

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“…[17] We also incorporated cyano and diketo functionalities in our design for the drug selectivity role of the cyano, as in remdesivir, against viral polymerases with no toxicity detected, [19] and for the inhibitory efficacy of ketone compounds against NS2B-NS3 West Nile virus protease [20] and Mayaro virus. [21] Encouraged by those features, we designed a model that integrated all these moieties (pyrimidine, cyano, azo, sulfonamide, diketone) in one hybrid to get new spiropyrimidine compounds that were subjected to study their antiviral activity against human coronavirus 229E (HCoV-229E). To measure the interaction and stability of the protein-ligand complex in motion, molecular dynamics simulation studies were performed.…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, Brahman and coworkers demonstrated that the imidazole diazo derivatives have a binding affinity of −8.1 kcal/mol with the main protease (Mpro) or 3CLPro) of SARS‐CoV‐2 which is responsible for viral replication [17] . We also incorporated cyano and diketo functionalities in our design for the drug selectivity role of the cyano, as in remdesivir, against viral polymerases with no toxicity detected, [19] and for the inhibitory efficacy of ketone compounds against NS2B‐NS3 West Nile virus protease [20] and Mayaro virus [21] . Encouraged by those features, we designed a model that integrated all these moieties (pyrimidine, cyano, azo, sulfonamide, diketone) in one hybrid to get new spiropyrimidine compounds that were subjected to study their antiviral activity against human coronavirus 229E (HCoV‐229E).…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, Antiviral Evaluation, and Molecular Dynamics Simulation Studies of New Spirocyclic Thiopyrimidinones as Anti HCoV‐229E

Ragab

Sweed

Elrashidy

et al. 2022

Chemistry & Biodiversity

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The current pandemic threat presented by viral pathogens like SARS-CoV-2 (COVID-19) suggests that virus emergence and dissemination are not geographically confined. As a result, the quest for antiviral agents has become critical to control this pandemic. In the current study, we provide a novel family of spirocyclic thiopyrimidinone derivatives whose cytotoxicity and antiviral efficacy were investigated against human coronavirus 229E (HCoV-229E) as a model for the Coronaviridae family. We utilized MTT and cytopathic effect (CPE) inhibitory tests on green monkey kidney (vero-E6) cell lines. The new molecules showed varied degrees of antiviral activity against the vero-E6 cell lines with minimal cytotoxicity. With a high level of a selective index (SI = 14.8), compound 9 showed outstanding inhibitory ability and could effectively suppress the human coronavirus 229E. Molecular dynamics simulation (MD) studies were performed to measure the interaction and stability of the protein-ligand complex in motion. The MD results for the most active compound 9 explored remarkable interactions with the binding pockets of the main protease (Mpro) of SARS-CoV-2 enzyme confirming the results gained from in vitro experiments. ADMET properties were also predicted for all the tested compounds. All these results demonstrated that the novel spirocyclic thiopyrimidinone derivatives would have the potential to be safe, low-cost chemical compounds that might be used as a novel therapeutic option for Coronaviridae viruses like COVID-19.

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Evaluation of Antiviral Activity of Cyclic Ketones against Mayaro Virus

Cited by 6 publications

References 36 publications

Polyphenols from Maackia amurensis Heartwood Protect Neuronal Cells from Oxidative Stress and Prevent Herpetic Infection

Polyphenols from Maackia amurensis Heartwood Protect Neuronal Cells from Oxidative Stress and Prevent Herpetic Infection

An update on the development of antiviral against Mayaro virus: from molecules to potential viral targets

Design, Synthesis, Antiviral Evaluation, and Molecular Dynamics Simulation Studies of New Spirocyclic Thiopyrimidinones as Anti HCoV‐229E

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