Antiviral and Virucidal Activities of Uncaria tomentosa (Cat's Claw) against the Chikungunya Virus.

Uncaria tomentosa (UT) is a medicinal plant popularly known as cat's claw belonging to the Rubiaceae family that has been reported to display antiviral and anti-inflammatory activities. The chikungunya virus (CHIKV) outbreaks constitute a Brazilian public health concern. CHIKV infection develops an abrupt onset of fever, usually accompanied by a skin rash, besides incapacitating polyarthralgia. There is no vaccine available or treatment for CHIKV infection. The present study evaluates the hydroalcoholic extract of UT bark as a potential antiviral against CHIKV. The in vitro antiviral activity of the UT extract against the Brazilian CHIKV strain was assessed using quantitative reverse transcription polymerase chain reaction, flow cytometry, and plaque assay. Results obtained demonstrated that UT inhibits CHIKV infection in a dose-dependent manner. At the non-cytotoxic concentration of 100 µg/mL, UT exhibited antiviral activity above 90% as determined by plaque reduction assay, and it reduced the viral cytopathic effect. Similarly, a significant virucidal effect of 100 µg/mL UT was observed after 24 and 48 h post-infection. This is the first report on the antiviral activity of UT against CHIKV infection, and the data presented here suggests UT as a potential antiviral to treat CHIKV infection.

Antiviral, Cytoprotective, and Anti-Inflammatory Effect of Ampelozizyphus amazonicus Ducke Ethanolic Wood Extract on Chikungunya Virus Infection.

Chikungunya fever, a debilitating disease caused by Chikungunya virus (CHIKV), is characterized by a high fever of sudden onset and an intense arthralgia that impairs individual regular activities. Although most symptoms are self-limited, long-term persistent arthralgia is observed in 30-40% of infected individuals. Currently, there is no vaccine or specific treatment against CHIKV infection, so there is an urgent need for the discovery of new therapeutic options for CHIKF chronic cases. This present study aims to test the antiviral, cytoprotective, and anti-inflammatory activities of an ethanol extract (FF72) from Ampelozizyphus amazonicus Ducke wood, chemically characterized using mass spectrometry, which indicated the major presence of dammarane-type triterpenoid saponins. The major saponin in the extract, with a deprotonated molecule ion m/z 897 [M-H]-, was tentatively assigned as a jujubogenin triglycoside, a dammarane-type triterpenoid saponin. Treatment with FF72 resulted in a significant reduction in both virus replication and the production of infective virions in BHK-21-infected cells. The viability of infected cells was assessed using an MTT, and the result indicated that FF72 treatment was able to revert the toxicity mediated by CHIKV infection. In addition, FF72 had a direct effect on CHIKV, since the infectivity was completely abolished in the presence of the extract. FF72 treatment also reduced the expression of the major pro-inflammatory mediators overexpressed during CHIKV infection, such as IL-1ß, IL-6, IL-8, and MCP-1. Overall, the present study elucidates the potential of FF72 to become a promising candidate of herbal medicine for alphaviruses infections.

Ethyl palmitate, an anti-chikungunya virus principle from Sauropus androgynus, a medicinal plant used to alleviate fever in ethnomedicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Sauropus androgynus is a medicinal shrub used for the treatment of fever in ethnomedical traditions in various Southeast Asian countries. AIM OF THE STUDY: This study was aimed to identify antiviral principles from S. androgynus against Chikungunya virus (CHIKV), a major mosquito-borne pathogen that re-emerged in the last decade, and to unravel their mechanism of action. MATERIALS AND METHODS: Hydroalcoholic extract of S. androgynus leaves was screened for anti-CHIKV activity using cytopathic effect (CPE) reduction assay. The extract was subjected to activity guided isolation and the resultant pure molecule was characterized by GC-MS, Co-GC and Co-HPTLC. The isolated molecule was further evaluated for its effect by plaque reduction assay, Western blot and immunofluorescence assays. In silico docking with CHIKV envelope proteins and molecular dynamics simulation (MD) analyses were used to elucidate its possible mechanism of action. RESULTS: S. androgynus hydroalcoholic extract showed promising anti-CHIKV activity and its active component, obtained by activity guided isolation, was identified as ethyl palmitate (EP), a fatty acid ester. At 1 µg/mL, EP led to 100% inhibition of CPE and a significant 3 log10 reduction in CHIKV replication in Vero cells at 48 h post-infection. EP was highly potent with an EC50 of 0.0019 µg/mL (0.0068 µM) and a very high selectivity index. EP treatment significantly reduced viral protein expression, and time of addition studies revealed that it acts at the stage of viral entry. A strong binding to the viral envelope protein E1 homotrimer during entry, thus preventing viral fusion, was identified as a possible mechanism by which EP imparts its antiviral effect. CONCLUSIONS: S. androgynus contains EP as a potent antiviral principle against CHIKV. This justifies the use of the plant against febrile infections, possibly caused by viruses, in various ethnomedical systems. Our results also prompt more studies on fatty acids and their derivatives against viral diseases.

Vathasura Kudineer, an Andrographis based polyherbal formulation exhibits immunomodulation and inhibits chikungunya virus (CHIKV) under invitro conditions.

ETHNOPHARMACOLOGICAL RELEVANCE: Chikungunya disease (CHIKD) is caused by the alphavirus, chikungunya virus (CHIKV) and is characterized by acute fever and joint inflammation; the inflammation continues even after clearance of the virus from the system, persisting for several months to years. Currently, there are no modern medicines/vaccines available for its treatment and use of over-the-counter anti-inflammatory generic medicines to relieve symptoms is generally practiced. In India, Indian traditional medicines hold a lot of promise to treat this infection and are routinely used during outbreaks. AIM OF THE STUDY: In the present study, we characterized the phytochemical and physicochemical properties of aqueous and ethanol extracts of the Vathasura Kudineer (VSK), a Andrographis based Siddha polyherbal formulation. Additionally, we evaluated its immunomodulatory and antiviral potential using an in vitro system. MATERIALS AND METHODS: Aqueous and ethanolic extracts of VSK were prepared and their physico and phytochemical properties were obtained by biochemical and biophysical assays, HPTLC and FTIR. The aqueous extracts of VSK and several of its ingredients were evaluated for their cytotoxicity in Vero cells and using the maximum non-toxic concentration (MNTC), were processed further for evaluating their ability to inhibit CHIKV infection in Vero cells. We performed the co-treatment assay with ethanol extract of VSK and several of its ingredients to assess the antiviral activity against chikungunya virus on Vero cells and through pre-treatment assay (anti-adhesive effect), co-incubation assay (virucidal effect) and post-treatment assay (post-entry effect) were evaluated. Further, we tested the aqueous extract of VSK along with some of its ingredients for their immunomodulatory properties. We performed antioxidant and anti-inflammatory assays using LPS-simulated RAW 264.7 cells. For antioxidant capacity of extracts, we performed extra-cellular ABTS radical scavenging activity and intra-cellular effects on ROS generation and SOD activity. We assessed the effect on most important inflammatory mediators like Nitric oxide (NO) and Prostaglandin E2 (PGE2) and pro-inflammatory cytokines like interleukin-1 beta (IL-1ß) and tumor necrosis factor alpha (TNFα). RESULTS: We provided the fingerprint of the phytochemicals of both ethanol and aqueous extracts of VSK that can be used for identification. We observed that ethanol extract was able to inhibit CHIKV infection at MNTC with 48 h of treatment on Vero cells. Its ingredient VSKI-As (Anethum sowa) found to be most effective to show virucidal effect while VSKI-Cs (Clerodendrum serratum) and VSKI-Pn (Pipper nigrum) found to be effective in post-entry effect. VSK was able to show ABTS radical scavenging activity, reduce ROS generation, inhibit the inflammatory mediators (NO and PGE2) and pro-inflammatory cytokines (IL-1ß and TNFα) production in LPS-stimulated RAW 264.7 cells. CONCLUSIONS: We provided the evidence that VSK has both immunomodulatory as well as antiviral potential. It shows virucidal as well as post-entry effects on chikungunya virus. VSK can inhibit pro-inflammatory cytokines, IL-1ß and TNFα production by suppressing the inflammatory mediators, NO and PGE2.

Effect of Sauropus androgynus L. Merr. on dengue virus-2: An in vitro and in silico study.

ETHNOPHARMACOLOGICAL RELEVANCE: Sauropus androgynus L. Merr. (Euphorbiaceae) commonly known as "multigreen" and "multivitamin" is consumed as a vegetable and used in traditional medicine to relieve fever. AIM OF THE STUDY: This in vitro study is aimed to explore the activities of the lipophilic fraction of the leaves of S. androgynus (LFSA) against dengue (DENV), chikungunya (CHIKV) viruses and malaria (P. falciparum strain 3D7) parasite. MATERIALS AND METHODS: The LFSA was analyzed by using GC-FID and GC-MS. The antiviral activity of LFSA was studied using the Vero CCL-81 cell line. The cytotoxicity assay was performed using 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). Focus forming unit (FFU), cell-based immunofluorescence (IFA) assays, and quantitative RT-PCR, were used to determine and confirm antiviral activity against DENV and CHIKV. The antiparasitic activity of LFSA was carried out against P. falciparum strain 3D7 grown in fresh O+ human erythrocytes culture. RESULTS: Twelve compounds were identified in LFSA using GC/MS. The most abundant compound was squalene (36.9%), followed by vitamin E (12.5%) and linolenic acid (10.2%). Significant reduction in DENV titre was observed under pre- and post-infection treatment conditions at a concentration of 31.25 µg/ml, but no anti-malarial and anti-CHIKV activity was observed. The Autodock-Vina-based in-silico docking study revealed that ß-sitosterol could form a strong interaction with the DENV E glycoprotein. CONCLUSION: Our findings suggest that LFSA can inhibit DENV infection and might act as a potent prophylactic/therapeutic agent against DENV-2. In-silico results suggested that ß-sitosterol may block the viral entry by inhibiting the fusion process.

Treatment with biological therapy is associated with faster recovery and lower frequency of treatment switch among rheumatic patients with Chikungunya fever.

BACKGROUND/OBJECTIVE: The effects of Chikungunya virus (CHIKV) infection on patients with rheumatic diseases have not been extensively studied. Our aim was to compare the clinical course of patients with rheumatoid arthritis and spondyloarthritis, categorized according to the use or not of biologic disease modifying anti-rheumatic drugs (bDMARDs), during and after infection by CHIKV. METHODS: Patients from a northeastern Brazilian city that suffered an epidemic outbreak of Chikungunya fever (CHIK) between Oct 2015 and Jul 2016, on regular follow-up in a longitudinal registry of rheumatic patients (BiobadaBrasil), were invited to participate. Participants underwent a standardized clinical interview and collection of blood sample for serological tests (IgM/IgG) for CHIKV. A positive IgG was considered evidence of previous CHIKV infection. RESULTS: 105 patients (84 with rheumatoid arthritis, 17 with ankylosing spondylitis, and 4 with psoriatic arthritis) were evaluated. Most patients (58, 55.2%) were on therapy with bDMARDs. The overall prevalence of seropositivity for CHIKV was 47.6% (39.7% in patients on bDMARDs and 57.4% in those exclusively on conventional synthetic (cs-) DMARDs (p = 0.070). Among seropositive patients, asymptomatic disease had similar frequency in those treated and not treated with bDMARDs (39.1% versus 33.3%, respectively; p = 0.670). However, patients exclusively on csDMARDs presented significantly higher prevalence of articular symptoms beyond 3 months and switched treatment more often than patients on bDMARDs (p < 0.05 for both comparisons). CONCLUSIONS: Among rheumatic patients with CHIK, those on bDMARDs had shorter persistence of articular symptoms and switched treatment scheme less often than patients exclusively treated with csDMARDs.

In vitro antiviral activity of piperidine alkaloids from Senna spectabilis flowers on Chikungunya virus infection.

BACKGROUND: Chikungunya fever is an endemic disease caused by the Chikungunya virus (CHIKV). To date there is no antiviral treatment against this infection or licensed vaccine to prevent it. Our study aims to evaluate whether (-)-cassine (1) and (-)-spectaline (2), the main alkaloids of Senna spectabilis, display anti-CHIKV activity. Both compounds have been described to be biologically active against neglected tropical diseases, including malaria, leishmaniasis, and schistosomiasis, which emphasizes that these molecules could be repurposed for chikungunya fever treatment. METHODS: The structures of the isolated compounds 1 and 2 were identified by NMR and HRESIMS analyses, and their antiviral activity against CHIKV was assessed by a dose-response assay employing BHK-21 cells and CHIKV-nanoluc, a recombinant virus carrying the nanoluciferase gene reporter. RESULTS: Compound 1 presented CC50 of 126.5 µM and EC50 of 14.9 µM, while compound 2 presented CC50 of 91.9 µM and EC50 of 8.3 µM. The calculated selectivity index (SI) was 8.5 for 1 and 11.3 for 2. CONCLUSION: The data presented herein show that compounds 1 and 2 have potential for being repurposed as anti-CHIKV drug. Our promising in vitro results encourage further in vitro and in vivo assays. This is the first description of the antiviral activity of compounds 1 and 2 against CHIKV infection, which can impact the development of antiviral drug candidates against chikungunya fever, which sometimes can be debilitating.

Plants extracts from Cameroon pharmacopeia strongly inhibit the Chikungunya virus infection by targeting entry and replication steps.

ETHNOPHARMACOLOGICAL RELEVANCE: Cameroon is one of the sub-Saharan African countries affected by Chikungunya virus (CHIKV). With the absence of approved treatment, this disease represents globally a major public health concern. Several plants are traditionally used in Cameroon for the treatment of virus induced fever and arthralgia. But to date there is no study that validate the efficacy of these plants for the treatment of Chikungunya virus infection. AIM OF THE STUDY: This study aims to explore the inhition effect, mechanism of action of plant extracts against Chikungunya virus. MATERIAL AND METHODS: An ethnobotanical survey conducted in some regions of Cameroon, led to the identification of nine medicinal plants used in traditional medicine for the healing of fever-related diseases and arthritis. Crude hydro-ethanolic extracts of each plant were prepared by maceration and their effects against CHIKV infection were investigated. CHIKV S27 strain was used to infection in Vero cell line. The antiviral activities were determined by plaque assay and/or RT-PCR targeting E1 envelope gene of CHIKV. Dose-response studies of the active plants were also determined by flow cytometry and Western blot. RESULTS: Four extracts, Entada africana Guill et Pers. (E4), Entandrophragma cylindricum Sprague (EI), Khaya grandifoliola C. D.C. Sapindales (E2) and Macaranga hurifolia Beille (E6) showed antiviral activity with the half-maximal inhibitory concentration of 8.29; 8.14; 12.81 and 26.89 µg/mL respectively. All extracts were nontoxic up to the concentration of 100 µg/µL. Entandrophragma cylindricum Sprague (EI), Khaya grandifoliola C. D.C. Sapindales (E2), and Entada africana Guill et Pers. (E4) showed strong inhibition on the entry step of viral infection. At the same time, only Entandrophragma cylindricum Sprague (EI) inhibited the viral titer significantly in replication and intercellular assembly steps. Four plant extracts namely Entandrophragma cylindricum Sprague (EI), Macaranga hurifolia Beille (E6), Phragmentera capitata (Sprengel) Balle (E12), and Detarium microcarpum (E13) were effective against egression step. CONCLUSIONS: Together, the results of this study showed anti-chikungunya activities of Entandrophragma cylindricum Sprague (EI) and Macaranga hurifolia Beille (E6), with therapeutics perspectives and can be promising sources of the development of anti-CHIKV molecule in future.

In Vitro Antiviral Activity of Potential Medicinal Plant Extracts Against Dengue and Chikungunya Viruses.

Dengue and chikungunya are two important mosquito-borne infections which are known to occur extensively in tropical and subtropical areas. Presently, there is no treatment for these viral diseases. In vitro antiviral screening of 25 extracts prepared from the plants of Vitex negundo, Plumeria alba, Ancistrocladus heyneanus, Bacopa monnieri, Anacardium occidentale, Cucurbita maxima, Simarouba glauca, and Embelia ribes using different solvents and four purified compounds (anacardic acid, chloroquinone, glaucarubinone, and methyl gallate) were carried out for their anti-dengue virus (DENV) and anti-chikungunya virus (CHIKV) activities. Maximum nontoxic concentrations of the chloroform, methanol, ethyl acetate, petroleum ether, dichloromethane, and hydroalcoholic extracts of eight plants were used. The antiviral activity was assessed by focus-forming unit assay, quantitative real-time RT-PCR, and immunofluorescence assays. Extracts from Plumeria alba, Ancistrocladus heyneanus, Bacopa monnieri, and Cucurbita maxima showed both anti-DENV and CHIKV activity while extract from Vitex negundo showed only anti-DENV activity. Among the purified compounds, anacardic acid, chloroquinone and methyl gallate showed anti-dengue activity while only methyl gallate had anti-chikungunya activity. The present study had identified the plant extracts with anti-dengue and anti-chikungunya activities, and these extracts can be further characterized for finding effective phytopharmaceutical drugs against dengue and chikungunya.

Endemic and Indigenous Plants from Mascarene Islands with Antiviral Propensities.

BACKGROUND: Antiviral resistance and inefficiency of available antiviral drugs to effectively treat viral infections have prompted many researchers worldwide to explore medicinal plants and their isolated compounds as alternative antivirals. The rich flora from the Mascarene Islands has also been thoroughly studied for their wide therapeutic activities, including their antiviral properties. OBJECTIVE: The aim of this review is to highlight the antiviral propensities of Mascarene endemic and indigenous medicinal plants. METHODOLOGY: A review of the literature was conducted via major databases and other primary sources of information. The inhibitory concentration/effective dose causing 50% viral inhibition (IC50/ED50), cytotoxic concentration causing 50% reduction in cell viability (CC50), and selectivity index (SI) were reported, and mechanisms of antiviral action were also discussed. RESULTS: Stillingia lineata was the most effective against chikungunya virus (SI: 10.9), and among its isolated compounds, 12-O-acetylphorbol-13(2″-methyl)- butyrate and 12-deoxyphorbol- 13(2″-methyl)butyrate were the most potent and selective inhibitors of chikungunya virus replication (SI: 41 and >240, respectively). 12-O-acetylphorbol-13(2″-methyl)- butyrate, 12ß-O-[nona- 2Z,4E,6E-trienoyl]-4α-deoxyphorbol-13-butyrate, 12-deoxyphorbol-13(2″-methyl)butyrate, and 12-deoxyphorbol-13-[8'-oxohexadeca-2E,4E,6E-trienoate showed strong selective antiviral effect on human immunodeficiency virus-I (SI: 36-899) and II (SI: 33-2056). Obetia ficifolia and Erythroxylon laurifolium were most active against the herpes virus (SI: 18.5 and 16, respectively). Labourdonnaisia glauca showed potent anti-poliovirus activity (SI: 40), while Badula insularis, Labourdonnaisia glauca and Myonima violacea were active against rhinovirus (SI: 1.3-2.5). Both anti-zika and anti-dengue virus activities were reported for Aphloia theiformis, Doratoxylon apetalum, Phyllanthus phillyreifolius and Psiloxylon mauritianum. CONCLUSION: Promising spectrum of antiviral properties notably against zika, dengue, chikungunya, polio-, rhino-, herpes, and human immunodeficiency viruses were presented by the Mascarene plants suggesting them as viable candidates for the potential development of effective natural antiviral drugs.

Demystifying therapeutic potential of medicinal plants against chikungunya virus.

Viral infections are posing a great threat to humanity for the last few years. Among these, Chikungunya which is a mosquito-borne viral infection has produced enormous epidemics around the world after been rebounded. Although this infection shows a low mortality rate, patients suffer from fever, arthralgia, and maculopapular rashes, which reduce the quality of life for several weeks to years. The currently available treatments only provide symptomatic relief based on analgesics, antipyretics, and anti-inflammatory drugs which are nonspecific without satisfactory results. Medicinal plants are a widely accepted source of new molecules for the treatment of infectious diseases including viral infections. The scientific reports, primarily focusing on the anti-chikungunya activity of plant extracts, natural origin pure compounds, and their synthetic analog published from 2011 to 2021, were selected from PubMed, Google Scholar, and Scopus by using related keywords like anti-chikungunya plants, natural antivirals for Chikungunya. The present review decodes scientific reports on medicinal plants against chikungunya virus (CHIKV) infection and demystifies the potential phytoconstituents which reveals that the screening of flavonoids containing plants and phytochemicals showing efficacy against other arbovirus infections, may prove as a potential lead for drug development against CHIKV. The present article also outlines pathogenesis, clinical aspects, molecular virology, and diagnostic approaches of CHIKV infection.

The Future of Carica papaya Leaf Extract as an Herbal Medicine Product.

Carica papaya (papaya) leaf extract has been used for a long time in a traditional medicine to treat fever in some infectious diseases such as dengue, malaria, and chikungunya. The development of science and technology has subsequently made it possible to provide evidence that this plant is not only beneficial as an informal medication, but also that it has scientifically proven pharmacological and toxicological activities, which have led to its formal usage in professional health care systems. The development of formulations for use in nutraceuticals and cosmeceuticals has caused this product to be more valuable nowadays. The use of good manufacturing practice (GMP) standards, along with the ease of registering this product facilitated by policies of the national government, will absolutely increase the value of papaya leaf extract as a vital nutraceutical and cosmeceutical products in the near future. In this article, we review the potential of papaya leaf extract to be a high-value commodity in terms of its health effects as well as its industrial benefits.

Evaluation of novobiocin and telmisartan for anti-CHIKV activity.

Chikungunya has re-emerged as an epidemic with global distribution and high morbidity, necessitating the need for effective therapeutics. We utilized already approved drugs with a good safety profile used in other diseases for their new property of anti-chikungunya activity. It provides a base for a fast and efficient approach to bring a novel therapy from bench to bedside by the process of drug-repositioning. We utilized an in-silico drug screening with FDA approved molecule library to identify inhibitors of the chikungunya nsP2 protease, a multifunctional and essential non-structural protein required for virus replication. Telmisartan, an anti-hypertension drug, and the antibiotic novobiocin emerged among top hits on the screen. Further, SPR experiments revealed strong in-vitro binding of telmisartan and novobiocin to nsP2 protein. Additionally, small angle x-ray scattering suggested binding of molecules to nsP2 and post-binding compaction and retention of monomeric state in the protein-inhibitor complex. Protease activity measurement revealed that both compounds inhibited nsP2 protease activity with IC50 values in the low micromolar range. More importantly, plaque formation assays could show the effectiveness of these drugs in suppressing virus propagation in host cells. We propose novobiocin and telmisartan as potential inhibitors of chikungunya replication. Further research is required to establish the molecules as antivirals of clinical relevance against chikungunya.

Macrocyclic Diterpenoids from Euphorbiaceae as A Source of Potent and Selective Inhibitors of Chikungunya Virus Replication.

Macrocyclic diterpenoids produced by plants of the Euphorbiaceae family are of considerable interest due to their high structural diversity; and their therapeutically relevant biological properties. Over the last decade many studies have reported the ability of macrocyclic diterpenoids to inhibit in cellulo the cytopathic effect induced by the chikungunya virus. This review; which covers the years 2011 to 2019; lists all macrocyclic diterpenoids that have been evaluated for their ability to inhibit viral replication. The structure-activity relationships and the probable involvement of protein kinase C in their mechanism of action are also detailed.

Current Strategies for Inhibition of Chikungunya Infection.

Increasing incidences of Chikungunya virus (CHIKV) infection and co-infections with Dengue/Zika virus have highlighted the urgency for CHIKV management. Failure in developing effective vaccines or specific antivirals has fuelled further research. This review discusses updated strategies of CHIKV inhibition and provides possible future directions. In addition, it analyzes advances in CHIKV lifecycle, drug-target development, and potential hits obtained by in silico and experimental methods. Molecules identified with anti-CHIKV properties using traditional/rational drug design and their potential to succeed in subsequent stages of drug development have also been discussed. Possibilities of repurposing existing drugs based on their in vitro findings have also been elucidated. Probable modes of interference of these compounds at various stages of infection, including entry and replication, have been highlighted. The use of host factors as targets to identify antivirals against CHIKV has been addressed. While most of the earlier antivirals were effective in the early phases of the CHIKV life cycle, this review is also focused on drug candidates that are effective at multiple stages of its life cycle. Since most of these antivirals require validation in preclinical and clinical models, the challenges regarding this have been discussed and will provide critical information for further research.

In Vivo Evaluation of Withania somnifera-Based Indian Traditional Formulation ( Amukkara Choornam), Against Chikungunya Virus-Induced Morbidity and Arthralgia.

Chikungunya viral fever results in extreme morbidity and arthralgia in affected individuals. Currently, modern medicines providing symptomatic relief for the acute febrile phase and the chronic arthritic phase are only options available. Traditional Indian medical system, however, uses specific formulations for treatment of this infection; one such polyherbal formulation used to treat the postpyretic phase of chikungunya is amukkara choornam. The current study was undertaken to study the efficacy of amukkara choornam in the treatment of chikungunya in C57BL/6J mice. The formulation when administered to chikungunya-infected mice relieved morbidity and joint swelling. Analysis of virus clearance in brain and joint tissues on formulation treatment revealed a direct correlation of viral load in brain to morbidity during infection; likewise, joint swelling receded prior to complete viral clearance explaining possible immunomodulatory effect of amukkara choornam. This study provides insight into the possible mode of action of amukkara choornam during chikungunya.

Antiviral effect of compounds derived from the seeds of Mammea americana and Tabernaemontana cymosa on Dengue and Chikungunya virus infections.

BACKGROUND: The transmission of Dengue virus (DENV) and Chikungunya virus (CHIKV) has increased worldwide, due in part to the lack of a specific antiviral treatment. For this reason, the search for compounds with antiviral potential, either as licensed drugs or in natural products, is a research priority. The objective of this study was to identify some of the compounds that are present in Mammea americana (M. americana) and Tabernaemontana cymosa (T. cymosa) plants and, subsequently, to evaluate their cytotoxicity in VERO cells and their potential antiviral effects on DENV and CHIKV infections in those same cells. METHODS: Dry ethanolic extracts of M. americana and T. cymosa seeds were subjected to open column chromatographic fractionation, leading to the identification of four compounds: two coumarins, derived from M. americana; and lupeol acetate and voacangine derived from T. cymosa.. The cytotoxicity of each compound was subsequently assessed by the MTT method (at concentrations from 400 to 6.25 µg/mL). Pre- and post-treatment antiviral assays were performed at non-toxic concentrations; the resulting DENV inhibition was evaluated by Real-Time PCR, and the CHIKV inhibition was tested by the plating method. The results were analyzed by means of statistical analysis. RESULTS: The compounds showed low toxicity at concentrations ≤ 200 µg/mL. The compounds coumarin A and coumarin B, which are derived from the M. americana plant, significantly inhibited infection with both viruses during the implementation of the two experimental strategies employed here (post-treatment with inhibition percentages greater than 50%, p < 0.01; and pre-treatment with percentages of inhibition greater than 40%, p < 0.01). However, the lupeol acetate and voacangine compounds, which were derived from the T. cymosa plant, only significantly inhibited the DENV infection during the post-treatment strategy (at inhibition percentages greater than 70%, p < 0.01). CONCLUSION: In vitro, the coumarins are capable of inhibiting infection by DENV and CHIKV (with inhibition percentages above 50% in different experimental strategies), which could indicate that these two compounds are potential antivirals for treating Dengue and Chikungunya fever. Additionally, lupeol acetate and voacangine efficiently inhibit infection with DENV, also turning them into promising antivirals for Dengue fever.

Investigation of twenty selected medicinal plants from Malaysia for anti-Chikungunya virus activity

Chikungunya virus is a reemerging arbovirus transmitted mainly by Aedes mosquitoes. As there are no specific treatments available, Chikungunya virus infection is a significant public health problem. This study investigated 120 extracts from selected medicinal plants for anti-Chikungunya virus activity. The plant materials were subjected to sequential solvent extraction to obtain six different extracts for each plant. The cytotoxicity and antiviral activity of each extract were examined using African monkey kidney epithelial (Vero) cells. The ethanol, methanol and chloroform extracts of Tradescantia spathacea (Commelinaceae) leaves showed the strongest cytopathic effect inhibition on Vero cells, resulting in cell viabilities of 92.6% ± 1.0% (512 µg/ml), 91.5% ± 1.7% (512 µg/ml) and 88.8% ± 2.4% (80 µg/ml) respectively. However, quantitative RT-PCR analysis revealed that the chloroform extract of Rhapis excelsa (Arecaceae) leaves resulted in the highest percentage of reduction of viral load (98.1%), followed by the ethyl acetate extract of Vernonia amygdalina (Compositae) leaves (95.5%). The corresponding 50% effective concentrations (EC50) and selectivity indices for these two extracts were 29.9 ± 0.9 and 32.4 ± 1.3 µg/ml, and 5.4 and 5.1 respectively. Rhapis excelsa and Vernonia amygdalina could be sources of anti-Chikungunya virus agents (AU)

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Management and Treatment of Dengue and Chikungunya - Natural Products to the Rescue.

Neglected tropical diseases (NTDs) flourish mostly in impoverished developing nations of the world. It is estimated that NTDs plague up to 1 billion people every year thereby inducing a massive economic and health burden worldwide. Following explosive outbreaks mostly in Asia, Latin America, Europe and the Indian Ocean, two common NTDs namely, Chikungunya and Dengue both transmitted by an infected mosquito vector principally Aedes aegypti have emerged as a major public health threat. Given the limitations of conventional medicine in specifically targeting the Chikungunya and Dengue virus (CHIKV and DENV), natural products present an interesting avenue to explore in the quest of developing novel anti; mosquito, CHIKV and DENV agents. In this endeavor, a number of plant extracts, isolated phytochemicals, essential oils and seaweeds have shown promising larvicidal and insecticidal activity against some mosquito vectors as well as anti CHIKV and DENV activity invitro. Other natural products that have depicted good potential against these diseases include; the symbiotic bacterial genus Wolbachia which can largely reduce the life span and infectivity of mosquito vectors and the marine Cyanobacterium Trichodesmium erythraeum which has shown anti- CHIKV activity at minimal cytotoxic level. The impetus of modern drug discovery approaches such as high throughput screening, drug repositioning, synthesis and computer-aided drug design will undeniably enhance the process of developing more stable lead molecules from natural products which have shown promising antiviral activity in-vitro.

Curcumin and Boswellia serrata gum resin extract inhibit chikungunya and vesicular stomatitis virus infections in vitro.

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes chikungunya fever and has infected millions of people mainly in developing countries. The associated disease is characterized by rash, high fever, and severe arthritis that can persist for years. CHIKV has adapted to Aedes albopictus, which also inhabits temperate regions including Europe and the United States of America. CHIKV has recently caused large outbreaks in Latin America. No treatment or licensed CHIKV vaccine exists. Traditional medicines are known to have anti-viral effects; therefore, we examined whether curcumin or Boswellia serrata gum resin extract have antiviral activity against CHIKV. Both compounds blocked entry of CHIKV Env-pseudotyped lentiviral vectors and inhibited CHIKV infection in vitro. In addition, vesicular stomatitis virus vector particles and viral infections were also inhibited to the same extent, indicating a broad antiviral activity. Although the bioavailability of these compounds is rather poor, they might be used as a lead structure to develop more effective antiviral drugs or might be used topically to prevent CHIKV spread in the skin after mosquito bites.