Siddha Medicine is a valuable therapeutic choice which is classically used for treating viral respiratory infections, this principle of medicine is proven to contain antiviral compounds.
The study is ...aimed to execute the In Silico computational studies of phytoconstituents of Siddha official formulation Kabasura Kudineer and novel herbal preparation - JACOM which are commonly used in treating viral fever and respiratory infectious diseases and could be affective against the ongoing pandemic novel corona virus disease SARS-CoV-2.
Cresset Flare software was used for molecular docking studies against the spike protein SARS-CoV-2 (PDB ID: 6VSB). Further, we also conducted insilico prediction studies on the pharmacokinetics (ADME) properties and the safety profile in order to identify the best drug candidates by using online pkCSM and SwissADME web servers.
Totally 37 compounds were screened, of these 9 compounds showed high binding affinity against SARS-CoV-2 spike protein. All the phytoconstituents were free from carcinogenic and tumorigenic properties. Based on these, we proposed the new formulation called as “SNACK–V”
Based on further experiments and clinical trials, these formulations could be used for effective treatment of COVID-19.
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•In silico Docking Studies of Kabasura Kudineer-Official Siddha Formulation and JACOM against SARS-CoV-2 spike protein.•37 Phytochemical constituents were docked to spike glycoprotein of SARS-COV-2 (PDB ID: 6VSB) by using Cresset Flare software.•Chrysoeriol and Luteolin from Kabasura Kudineer and Quercetin from JACOM shown the highest dock score values of above -11.00.•In silico ADME and drug Likeliness and synthetic accessibility were also carried out for phytoconstituents.
Currently, no vaccines or modern drugs are available for dengue and chikungunya and only symptomatic relief is provided to the patients. Siddha medicine, a traditional form of indigenous medical ...system uses specific polyherbal formulations for the treatment of such infections with considerable success. One such polyherbal formulation for the treatment of chikungunya and dengue is Nilavembu kudineer (NVK). The mechanistic details of this drug as an antiviral for chikungunya virus (CHIKV) and dengue virus (DENV) is poorly understood.
The current study was undertaken to study the efficacy of NVK as an antiviral formulation against CHIKV and DENV.
Cytotoxicity assays (MTT) were performed to determine the role of NVK as an antiviral during chikungunya and dengue infections in the following conditions-i). post infection, ii). during active infections and iii) protective, not allowing virus infection.
It was observed that NVK provides protection against CHIKV and DENV-2 during active infection as well can help to prevent virus infection in the cells and it mainly depends on the cellular availability of drugs for maximum protection against both the infections.
Our study establishes that extraction protocols are important to ensure maximum efficacy of NVK along with the time of addition of the drug during CHIKV and DENV infections in the cells. This study provides insights to the possible mode of action of NVK in in vitro condition during CHIKV and DENV infection.
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•Andrographis is a major component of Nilavembu kudineer.•Andrographis is more cytotoxic when used singularly and hence is used as a polyherbal formulation.•Ethanol Extract of Nilavembu Kudineer (NVK) exhibit antiviral properties.•NVK has a prophylactic effect during chikungunya and dengue virus (CHIKV and DENV respectively) infection.•NVK exhibits antiviral activity during active CHIKV and DENV infections.
Immunosenescence is a pertinent factor in the mortality rate caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The changes in the immune system are strongly associated with age ...and provoke the deterioration of the individual's health. Traditional medical practices in ancient India effectively deal with COVID-19 by boosting natural immunity through medicinal plants. The anti-inflammatory and antiviral properties of Glycyrrhiza glabra are potent in fighting against COVID-19 and promote immunity boost against the severity of the infection. Athimadhura Chooranam, a polyherbal formulation containing Glycyrrhiza glabra as the main ingredient, is recommended as an antiviral Siddha herb by the Ministry of AYUSH. This paper is intended to identify the phytoconstituents of Glycyrrhiza glabra that are actively involved in preventing individuals from COVID-19 transmission. The modulated pathways, enrichment study, and drug-likeness are calculated from the target proteins of the phytoconstituents at the pharmacological activity (Pa) of more than 0.7. Liquiritigenin and Isoliquiritin, the natural compounds in Glycyrrhiza glabra, belong to the flavonoid class and exhibit ameliorative effects against COVID-19. The latter compound displays a higher protein interaction to a maximum of six, out of which HMOX1, PLAU, and PGR are top-hub genes. ADMET screening further confirms the significance of the abovementioned components containing better drug-likeness. The molecular docking and molecular dynamics method identified liquiritigenin as a possible lead molecule capable of inhibiting the activity of the major protease protein of SARS-CoV-2. The findings emphasize the importance of in silico network pharmacological assessments in delivering cost-effective, time-bound clinical drugs.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmissions are occurring rapidly; it is raising the alarm around the globe. Though vaccines are currently available, the evolution and ...mutations in the SARS-CoV-2 threaten available vaccines' significance. The drugs are still undergoing clinical trials, and certain medications are approved for "emergency use" or as an "off-label" drug during the pandemic. These drugs have been effective yet accommodating side effects, which also can be lethal. Complementary and alternative medicine is highly demanded since it embraces a holistic approach. Since ancient times, natural products have been used as drugs to treat various diseases in the medical field and are still widely practiced. Medicinal plants contain many active compounds that serve as the key to an effective drug design. The Kabasura kudineer and Nilavembu kudineer are the two most widely approved formulations to treat COVID-19. However, the mechanism of these formulations is not well known. The proposed study used a network pharmacology approach to understand the immune-boosting mechanism by the Kabasura kudineer, Nilavembu kudineer, and JACOM in treating COVID-19. The plants and phytochemical chemical compounds in the Kabasura kudineer, Nilavembu kudineer, and JACOM were obtained from the literature. The Swiss target prediction algorithm was used to predict the targets for these phytochemical compounds. The common genes for the COVID-19 infection and the drug targets were identified. The gene-gene interaction network was constructed to understand the interactions between these common genes and enrichment analyses to determine the biological process, molecular functions, cellular functions, pathways involved, etc. Finally, virtual screening and molecular docking studies were performed to identify the most potential targets and significant phytochemical compounds to treat the COVID-19. The present study identified potential targets as ACE, Cathepsin L, Cathepsin B, Cathepsin K, DPP4, EGFR, HDAC2, IL6, RIPK1, and VEGFA. Similarly, betulinic acid, 5″-(2⁗-Hydroxybenzyl) uvarinol, antofine, (S)-1'-methyloctyl caffeate, (Z)-3-phenyl-2-propenal, 7-oxo-10α-cucurbitadienol, and PLX-4720 collectively to be potential treatment agents for COVID-19.
In peripheral blood, cell‐free DNA (cfDNA) contains circulating tumor DNA (ctDNA), which indicates molecular abnormalities in metastatic breast tumor tissue. The sequencing of cfDNA of Metastatic ...Breast Cancer (MBC) patients allows assessment of therapy response and noninvasive treatment. In the proposed study, clinically significant alterations in PIK3CA and TP53 genes associated with MBC resulting in a missense substitution of His1047Arg and Arg282Trp from an next‐generation sequencing‐based multi‐gene panel were reported in a cfDNA of a patient with MBC. To investigate the impact of the reported mutation, we used molecular docking, molecular dynamics simulation, network analysis, and pathway analysis. Molecular Docking analysis determined the distinct binding pattern revealing H1047R‐ATP complex has a higher number of Hydrogen bonds (H‐bonds) and binding affinity with a slight difference compared to the PIK3CA‐ATP complex. Following, molecular dynamics simulation for 200 ns, of which H1047R‐ATP complex resulted in the instability of PIK3CA. Similarly, for TP53 mutant R282W, the zinc‐free state (apo) and zinc‐bounded (holo) complexes were investigated for conformational change between apo and holo complexes, of which the holo complex mutant R282W was unstable. To validate the conformational change of PIK3CA and TP53, 80% mutation of H1047R in the kinase domain of p110α expressed ubiquitously in PIK3CA protein that alters PI3K pathway, while R282W mutation in DNA binding helix (H2) region of P53 protein inhibits the transcription factor in P53 pathway causing MBC. According to our findings, the extrinsic (hypoxia, oxidative stress, and acidosis); intrinsic factors (MYC amplification) in PIK3CA and TP53 mutations will provide potential insights for developing novel therapeutic methods for MBC therapy.
Traditional medicines are impactful in treating a cluster of respiratory-related illnesses. This paper demonstrates screening active, druggable phytoconstituents from a classical Siddha-based ...poly-herbal formulation called Swasa Kudori Tablet to treat asthma. The phytoconstituents of Swasa Kudori are identified as Calotropis gigantea, Piper nigrum, and (Co-drug) Abies webbiana. Active chemical compounds are extracted with the Chemical Entities of Biological Interest (ChEBI) database. The gene targets of each compound are identified based on the pharmacological activity using the DIGEP-Pred database. Thirty-two genes showing P
> 0.7 is screened, and the target markers are selected after performing gene overlap evaluation with the asthma genes reported in GeneCards and DisGeNET database. Ten markers are identified, such as ADIPOQ, CASP8, CAT, CCL2, CD86, FKBP5, HMOX1, NFE2L2, TIMP1, VDR, in common, listed as molecular targets. Pharmacokinetic assessment (ADME) revealed five natural drug compounds 2-5-7-trihydroxy-2-(4-hydroxyphenyl)-2,3-dihydro-4H-chromen-4-one, (+)-catechin-3'-methyl ether, futoenone, 5-hydroxy-4',7-dimethoxyflavanone, and pinocembrin showing better druggability. Further screening delineates the target (HMOX1) and drug (pinocembrin) for molecular docking evaluation. When docked with HO-1, Pinocembrin showed a binding affinity of -8.0 kcal/mol. MD simulation studies substantiate the docking studies as HO-1 in complex with pinocembrin remains stable in the simulated trajectory. The current findings exhibit the significance of traditional medicines as potential drug candidates against asthma.
In this research work, an attempt was made to machine the titanium (Ti6Al4V) alloy utilizing electric discharge machining technique. The distinct process parameters and its impact on the machining ...performance were identified using the cause-and-effect diagram (CED). The key process parameters identified by CED diagram were current, pulse on time (Ton), aluminium oxide (Al2O3) powder concentration, and gap distance; experiments were conducted by varying the process parameters, experimental runs were designed using the Taguchi mixed orthogonal array. The experimental results revealed that improvement in material removal rate (MRR) was due to the bridging effect; reduction in tool wear rate (TWR) owing to the expansion of spark gap and enhancement in the surface roughness (Ra) was due to the complete flushing of machined debris. The interaction impact was analysed using the contour plot and with the aid of mathematical modelling experimental fits that were identified and the results were validated utilizing the sensitivity analysis. The obtained results were optimized using the technique for order of preference by similarity to ideal solution (TOPSIS) optimization technique.
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.
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.
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-1β) and tumor necrosis factor alpha (TNFα).
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-1β and TNFα) production in LPS-stimulated RAW 264.7 cells.
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-1β and TNFα production by suppressing the inflammatory mediators, NO and PGE2.
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•VSK, an Andrographis based formulation has antiviral potential. VSK-EE showed both virucidal and post-entry effects.•Its ingredient, VSKI-As has most potential virucidal effect while VSKI-Cs were found to be most effective to show post-entry effect.•VSK-AE showed promising immunomodulatory effect in in vitro. It showed antioxidant as well as anti-inflammatory effect.•VSK was found to suppress immune mediators like NO and PGE2 thereby inhibiting proinflammatory cytokines, IL1β and TNFα.
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