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Mayaro virus (MAYV) is a neglected arthropod-borne virus found in the Americas. MAYV infection results in Mayaro fever, a non-lethal debilitating disease characterized by a strong inflammatory response affecting the joints and muscles. MAYV was once considered endemic to forested areas in Brazil but has managed to adapt and spread to urban regions...
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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]. ...
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.
... 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). ...
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.
... In continuation of our efforts to find beneficial antiviral compounds (De Oliveira et al., 2019;Fernandes et al., 2021) and considering the premises, we describe the preparation of vanillin derivatives in the present investigation bearing 1,2,3-triazole groups and the virucide effect of them on ZIKV. ...
The Zika virus (ZIKV) is an arbovirus and belongs to the Flaviviridae family and Flavivirus genus, with dissemination in the Americas. In Brazil, the predominant strain is the Asian, promoting outbreaks that started in 2015 and are directly related to microcephaly in newborns and Guillain-Barré syndrome in adults. Recently, researchers identified a new African strain circulating in Brazil at the mid-end of 2018 and the beginning of 2019, with the potential to originate a new epidemic. To date, there is no approved vaccine or drug for the treatment of Zika syndrome, and the development of therapeutic alternatives to treat it is of relevance. A critical approach is to use natural products when searching for new chemical agents to treat Zika syndrome. The present investigation describes the preparation of a series of 1,2,3-triazoles derived from the natural product vanillin and the evaluation of their virucide activity. A series of fourteen derivatives were prepared via alkylation of vanillin followed by CuAAC (the copper(I)-catalyzed azide-alkyne cycloaddition) reaction. The compounds were fully characterized by infrared (I.R.), nuclear magnetic resonance (NMR), and high-resolution mass spectrometry (HRMS) techniques. The cytotoxicity of Vero cells and the effect on the Zika Virus of the vanillin derivatives were evaluated. It was found that the most effective compound corresponded to 4-((1-(4-isopropylbenzyl)-1H-1,2,3-triazol-4-yl)methoxy)-3-methoxybenzaldehyde (8) (EC50 = 27.14 μM, IC50 = 334.9 μM). Subsequent assessments, namely pre and post-treatment assays, internalization and adsorption inhibition assays, kinetic, electronic microscopy analyses, and zeta potential determination, revealed that compound 8 blocks the Zika virus infection in vitro by acting on the viral particle. A molecular docking study was performed, and the results are also discussed.
... [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. ...
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 line. The new molecules showed varied degrees of antiviral activity against the vero‐E6 cell line 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 (Mpor) 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.
... Among them, the xanthenodiones stand out as anti-bactericidal, anti-leishmania, antifungal, antitumor, anti-trypanosome, and antiviral substances [153,154]. Several compounds of this group were produced from the mixture of 1,3-diketone, aldehyde, and ZrOCl 2 8H 2 O and evaluated during in vitro infection by MAYV [155]. Only one of them, compound 9, remained in the test, as it obtained the best SI (15.8) [156]. ...
... Only one of them, compound 9, remained in the test, as it obtained the best SI (15.8) [156]. However, when evaluating its anti-MAYV action, it was found to be effective only in pre-treatment or in high concentrations (338.8 µmol/L) [156], unlike what was verified for ZIKV, in which it interacts with viral envelope proteins preventing adsorption [155]. The likely mechanism of action is unclear, and it is believed that it may act on intracellular events. ...
Mayaro virus is an emerging arbovirus that causes nonspecific febrile illness or arthralgia syndromes similar to the Chikungunya virus, a virus closely related from the Togaviridae family. MAYV outbreaks occur more frequently in the northern and central-western states of Brazil; however, in recent years, virus circulation has been spreading to other regions. Due to the undifferentiated initial clinical symptoms between MAYV and other endemic pathogenic arboviruses with geographic overlapping, identification of patients infected by MAYV might be underreported. Additionally, the lack of specific prophylactic approaches or antiviral drugs limits the pharmacological management of patients to treat symptoms like pain and inflammation, as is the case with most pathogenic alphaviruses. In this context, this review aims to present the state-of-the-art regarding the screening and development of compounds/molecules which may present anti-MAYV activity and infection inhibition.
Introduction:
Mayaro fever is an emerging viral disease that manifests as an acute febrile illness. The disease is self-limiting, however joint pain can persist for months leading to chronic arthralgia. There is no specific treatment available, which ultimately leads to socioeconomic losses in populations at risk as well as strains to the public health systems.
Areas covered:
We reviewed the candidate treatments proposed for Mayaro virus (MAYV) infection and disease, including antiviral compounds targeting viral or host mechanisms, and pathways involved in disease development and pathogenicity. We assessed compound screening technologies and experimental infection models used in these studies and indicated the advantages and limitations of available technologies and intended therapeutic strategies.
Expert opinion:
Although several compounds have been suggested as candidate treatments against MAYV infection, notably those with antiviral activity, most compounds were assessed only in vitro. Compounds rarely progress toin vivo or preclinical studies, and such difficulty may be associated with limited experimental models. MAYV biology is largely inferred from related alphaviruses and reflected by few studies focusing on target proteins or mechanisms of action for MAYV. Therapeutic strategies targeting pathogenic inflammatory responses have shown potential against MAYV-induced disease in vivo, which might reduce long-term sequelae.
