Background Status of the latest developments from the spread of COVID-19 in Indonesia has reached 15438 cases with 1028 cases of patients died, updated on May 13, 2020. Unfortunately, the number of infected continues to overgrow, and no drugs have been approved for effective treatment. This research aims to find potential candidate compounds in Indonesian herbal as COVID-19 supportive therapy using machine learning and pharmacophore modeling approach. Methods For a machine learning approach, we used three classification methods that have different principles in decision making, such as SVM, MLP, and Random Forest. By using these different methods, it is expected that more optimal screening results can be obtained than using only one method. Moreover, for a pharmacophore modeling approach, we did the structure-based method on the 3D structure of SARS-CoV-2 main protease (3CLPro) and using known SARS, MERS, and SARS-CoV-2 repurposing drugs from literature as data sets on the ligand-based method. Lastly, we used molecular docking to analyse the interaction between 3CLpro (main protease) protein with 14 hit compounds from the Indonesian Herbal Database (HerbalDB) and Lopinavir as a positive control. Results The models yielded by SVM, RF, and MLP were used for screening in herbal compounds obtained from HerbalDB and got 125 potential compounds. Whereas the structure-based pharmacophore modeling gave eight hit compounds and the ligand-based methods produced more than a hundred hit compounds. Based on the screening on HerbalDB using these two prediction approaches, we got 14 hit compounds candidates. Further analysis was done using molecular docking to know the interaction between each compound and main protease of SARS-CoV-2 as inhibitory agents. From molecular docking analysis, we got six potential compounds as the main protease of SARS-CoV-2 inhibitor, i.e Hesperidin, Kaempferol-3,4'-di-O-methyl ether (Ermanin); Myricetin-3-glucoside, Peonidine 3-(4’-arabinosylglucoside); Quercetin 3-(2G-rhamnosylrutinoside); and Rhamnetin 3-mannosyl-(1–2)-alloside. Conclusions Herbal compounds from various plants were potential as candidates of SARS-CoV-2 antivirals. Based on our research and literature study, one of the potential commodity crops in Indonesia is Psidium guajava (guava) and can be directly used by the community.
Coronavirus disease 2019 (COVID-19) is an infectious disease of the respiratory system that caused a pandemic in 2020. There is still not any effective special treatment to cure it. Drug repositioning is used to find an effective drug for curing new diseases by finding new efficacy of registered drug. The new efficacy can be conducted by elaborating the interactions between compounds and proteins (DTI). Deep Semi-Supervised Learning (DSSL) is used to overcome the lack of DTI information. DSSL utilizes unsupervised learning algorithms such as Stacked Auto Encoder (SAE) as pre-training for initializing weights on the Deep Neural Network (DNN). This study uses DSSL with a feature-based chemogenomics approach on the data resulted from the exploration of potential anti-coronavirus treatment. This study finds that the use of fingerprints for compound features and Dipeptide Composition (DC) for protein features gives the best results on accuracy (0.94), recall (0.83), precision (0.817), F-measure (0.822), and AUROC (0.97). From the test data predictions, 1766 and 929 positive interactions are found on the test data and herbal compounds, respectively. Keywords-coronavirus disease 2019, drug repositioning, deep semi-supervised learning, stacked autoencoder, deep neural network II. DEEP SEMI-SUPERVISED LEARNING FOR DTIResearch on drug repositioning is based on the fact that most drug compounds can activate or inhibit the biological functions of the target protein. This creates the needs to develop a DTI identification system [11]. DTI identification
Ulcerative colitis (UC) is a part of incurable chronic inflammatory disease that has gained importance over the past few decades. A lot of research has been done to find effective treatments for UC, one of which is herbal medicine. Phaleria macrocarpa (PM), an Indonesian native plant, is thought to be an alternative therapy for UC because of its anti-inflammatory properties. Therefore, in this research, Phaleria macrocarpa Leaves Ethanol Extract (PMLEE) is used to assess its effect on UC by using Caspase-3 as apoptosis marker. PMLEE was made from dried material of PM that undergo maceration. Animals were separated into six groups: normal, negative control, positive control, and PMLEE groups (100, 200, 300 mg/kgBW). PMLEE was then injected to BALB/c mice that have been induced by dextran sodium sulphate (DSS) for 7 consecutive days. DSS is used to model UC in mice colon tissue. All animals were sacrificed and their colons were collected then stained with anti-Caspase-3. The stained sections were subsequently examined with ImageJ based on color intensity which generated H-Score as the results. Based on H-Score of each group, PMLEE 300mg has significantly upregulate the expression of Caspase-3 compare to the negative control (p=0.015). PMLEE also has a tendency to be dose dependent based on the significant difference between PMLEE doses. Therefore, it concludes that PMLEE is able to upregulate the expression of Caspase-3 in colon cells as in this study it was directly proportional.
Objective: Inflammatory disease occurs in the mucosal of the colon, or ulcerative colitis (UC) is one of subtypes of inflammatory bowel disease. The numerous of drug side effects for treatment of colitis give rise to use medicinal herbs as alternative therapies. Pomegranate peel extract has been used for the treatment of pain and inflammatory conditions. This study aimed to investigate the anti-inflammatory effects of pomegranate peel ethanol extract on mice colon through inflammation pathway which reduce inflammation score in mice model of chronic inflammation induced by dextran sodium sulfate (DSS).Methods: Thirty Swiss Webster mice divided randomly into 6 groups: Normal, aspirin 43 mg/kg/d (ASP), ellagic acid 26 mg/kg/d (ELG), DSS 2%b/v (DSS), pomegranate peel ethanol extract 240 mg/kg/d (DOSES-1), and 480 mg/kg/d (DOSES-2). All groups were given DSS 2% over 3 cycles except normal group (where each cycle in the DSS group consisted of 2% DSS in drinking water for 7 days, followed by a 7-day interval with normal drinking water). At the end of the experiment, colon samples were washed with water then buffered neutral formalin 10% fixed and paraffin embedded for histological analysis.Results: DOSES-1 and DOSES-2 were significantly reduced inflammation score in colon mice induced by DSS (p<0.05), mean score 2.01 and 2.02. Expression of cyclooxygenase (COX-2) was significantly decreased (p<0.05), mean score 27.48 and 17.77. Expression of iNOS was also significantly decreased (p<0.05), mean score 54.01 and 36.69. There were no significant differences between DOSES-1 and DOSES-2 groups with ASP and ELG group (p>0.05). Conclusion:Pomegranate peel ethanol extract has an anti-inflammatory agent by reduces inflammation score, inhibiting COX-2 and iNOS expression on mice colon by DSS induced. Furthermore, pomegranate peel ethanol extract has equivalent effectiveness with aspirin and pure ellagic acid.
Objective: The objective of this research was to investigate the anti-inflammatory effect of Mahkota Dewa fruit pericarp extract (Phaleria macrocarpa) on inducible nitric oxide synthase (iNOS) in mice colon induced by dextran sodium sulfate (DSS). Method:The simplisia of P. macrocarpa pericarp was weighed (1000 g) and extracted by maceration process. The total yield of the ethanolic extract was 26.43%. Phytochemical screening was carried out for the detection of the phytoconstituents by simple qualitative methods. The antiinflammatory activity was performed by DSS-induced colitis model through assessment of hematoxylin-eosin staining and expression of iNOS by immunohistochemistry assay at four different doses, i.e., 650, 1250, 2500, and 5000 mg/kg. Swiss Webster male mice weighing 25-30 g were used for the study.Results: Inflammation score in dose 625, 1250, 2500, and 5000 mg/kg were 1.63, 1.43, 1.32, and 2.20, respectively. This result is significantly different (p=0.008) with DSS group that was 4.37. The results of iNOS optical density score in dose 625, 1250, 2500, and 5000 mg/kg were 1.21, 1.119, 1.22, and 1.37, respectively. This result was significantly different (p=0.000) with DSS group that was 2.24. Conclusion:Pericarp extract of P. macrocarpa fruit exhibited anti-inflammatory activity in the experimental model shown by suppressing the expression of inflammatory cell and iNOS.
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