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COVID-19 has become a global pandemic since 2020. The search for promising drugs based on the abundant herbal ingredients in Indonesia is one of the breakthroughs. Curcumin is a chemical compound with various potentials such as antioxidant, anti-inflammatory and antiviral. We conducted a molecular docking analysis to determine the potential of curcumin against SARS-CoV-2 non-structural and structural proteins, such as the main protease and spike protein. This study used the compound of curcumin (PubChem CID: 969516) from Curcuma longa L. or turmeric and two Indonesian SARS-CoV-2 isolates that have been deposited in the GISAID database (hCoV-19/Indonesia/JI-PNF-217315/2021 - EPI_ ISL_12777089 or lineage B.1.617.2 and hCoV-19/Indonesia/JI-PNF-211373/2021 - EPI_ISL_6425649 or lineage B.1.470). In addition, we used molnupiravir (PubChem CID: 145996610) as a drug control. We performed molecular docking analysis with PyRx software 0.9.9 (academic license) and visualization of molecular docking results with PyMOL software 2.5.4 (academic license). The results of this study found that curcumin had good potential against main protease and spike protein compared to the drug (control). In summary, we suggested that curcumin is a potential drug candidate against SARS-CoV-2. However, there is a need for future wet laboratory-based pre-clinical research such as in vitro and in vivo.Copyright © 2023 Phcogj.Com.
ABSTRACT
Stress during Coronavirus disease-2019 (COVID-19) pandemic affects the physiological and immunological response to women's reproductive health. Meanwhile, Apium graveolens and Eucalyptus globulus are immunomodulators related to women's reproductive health. This investigation had a goal to examine the effectiveness of A. graveolens and E. globulus towards the expression of Heat Shock Protein-70 (HSP70) as the primary biomarker of stress, Tumor Necrosis Factor-Alpha (TNF-alpha) as a pro-inflammatory protein, along with Luteinizing Hormone (LH) and Growth Differentiation Factor 9 (GDF-9) as folliculogenesis markers. An experimental randomized controlled trial was utilized by using a pre-test and post-test control group design. Sixty women, who had stress based on DASS-21 questionnaire, were divided into two groups in Nusukan Health Center, Indonesia. The intervention group was orally administered with 300 mg A. graveolens capsules and E. globulus essential oil for 14 days, while the control group was given a placebo. Blood samples and stress levels were then evaluated before and after the intervention. No significant difference was found in the stress levels of the control and treatment groups at the pre-test. Meanwhile, the intervention group had the decreased HSP70, TNF-alpha, and stress levels (p<0.001). In contrast, increased LH and GDF-9 levels were displayed in the intervention group compared to the control group (p<0.001). These findings revealed that A. graveolens supplementation and E. globulus essential oil have the ability to decrease stress and are able to protect folliculogenesis markers on women's reproductive health due to stressful conditions during pandemic COVID-19. Copyright © 2022 by Indonesian Journal of Pharmacy (IJP).
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Context: COVID-19 was caused by the spread and transmission of SARS-CoV-2 at the end of 2019 until now. The problem comes when antiviral drugs have not yet been found and patients infected with SARS-CoV-2 can trigger a cytokine storm condition due to the effects of viral replication. Indonesia has various kinds of medicinal plants, such as Sonchus arvensis L., which are used as medicinal plants. Aim(s): To analyze the activity of the inhibitor as SARS-CoV-2 antiviral agents from n-hexane fractions of S. arvensis leaves. Method(s): The sample was collected from GC-MS analysis, PubChem, and Protein Databank database, then drug-likeness identification using Lipinski Rule of Five server and bioactive prediction of bioactive compounds as inhibitor activity was conducted by Molinspiration server. Furthermore, the docking simulation was performed using PyRx 0.9.9 software to determine the binding activity, molecular interaction by Discovery Studio software to identify position and interaction type, 3D molecular visualization by PyMol 2.5. software, and dynamic by CABS-flex 2.0 server to predict interaction stability. Result(s): alpha-Amyrin and beta-amyrin from n-hexane fractions of S. arvensis leaves had activity as SARS-CoV-2 inhibitors through interactions on helicase, RdRp, Mpro, and RBD-Spike, both compounds had more negative binding affinity than control drug and can produce stable chemical bond interactions in the ligand-protein complexes. However, the results were merely computational, so they must be validated through an in vivo and in vitro research approach. Conclusion(s): Sonchus arvensis L. leaves were predicted to have SARS-CoV-2 antiviral through inhibitor activity by alpha-amyrin and beta-amyrin. Copyright © 2022 Journal of Pharmacy & Pharmacognosy Research.
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The global COVID-19 pandemic caused by SARS-CoV-2 has been the resulted of massive human deaths since early 2020. The purpose of this study was to determine the potential of mangosteen (Garcinia mangostana L.) as an inhibitor of RBD spike, helicase, Mpro, and RdRp activity of SARS-CoV-2 with an in silico approach. The samples were obtained from PubChem and RCSB PDB. Analysis of the similarity of the drug was carried out with the Swiss ADME on the basis of Lipinski rule of five. Prediction of antivirus probabilities was carried out using PASS Online. Molecular screening was performed using PyRx through molecular docking. Discovery Studio was used for visualization. The bioactive compounds with the highest antiviral potential were indicated with the lowest binding affinity to the targeted proteins RBD spike, helicase, Mpro, and RdRp of SARS-CoV-2. The results indicated that mangiferin has the greatest potential as a potential antiviral. However, more research is required to validate the results of these computational predictions. Copyright © 2022 Phcogj.Com.
ABSTRACT
The aim of this study is to screen the content of bioactive compounds of Moringa oleifera and to identify its potential as an antiviral against COVID 19 through an entry inhibitor mechanism using bioinformatics tools. The sample was obtained from PubChem database. Amino acis sequences were obtained from the NCBI. Protein modeling is made through the SWISSMODEL site. The target proteins for this study were SARS-CoV-2 Mpro and RdRp. The protein-inhibitory interaction of the drug from M. oleifera bioactive compounds to SARS-CoV-2 was predicted by molecular docking with PyRx software.The result shows that M. oleifera was a potential antiviral candidate for SARS-CoV-2 with an entry inhibitor mechanism through a compound, especially quercetin. The RFMS value of both interactions between Mpro and quercetion and RdRp with quercetin were not higher than 1.05. This result still needed further research to prove this prediction. Copyright © 2022 Phcogj.Com. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
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COVID-19 pandemic has no immediate ending in sight, and any significant increasing cases were observed worldwide. Currently, there are only two main strategies for developing COVID-19 drugs that predominantly use a proteomics-based approach, which are drug repurposing and herbal medicine strategies. However, a third strategy has existed, called small interfering RNA or siRNA, which is based on the transcriptomics approach. In the case of SARS-CoV-2 infection, it is expected to perform by silencing the viral gene, which brings the surface glycoprotein (S) gene responsible for SARS-CoV-2 viral attachment to the ACE2 receptor on the human host cell. This third approach applies a molecular simulation method comprising data retrieval, multiple sequence alignment, phylogenetic tree depiction, 2D/3D structure prediction, and RNA-RNA molecular docking. The expected results are the prediction of 2D and 3D structures of both siRNA and mRNA silenced S genes along with a complex as the result of a docking method formed by those silenced genes. An Insilco chemical interaction study was performed in testing siRNA and mRNA complex’s stability with the confirmation result of a stable complex which is expected to be formed before mRNA reaches the ribosome for the translation process. Thus, siRNA from the S gene could be considered a candidate for the COVID-19 therapeutic agent. © 2022, Gadjah Mada University. All rights reserved.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the COVID-19 pandemic that infects humans and attacks the body's immune system. The purpose of the study was to identify the potential of bioactive compounds in purslane (Portulaca oleracea L.) and star anise (Illicium verum Hook) via a dual inhibitor mechanism against SARS-CoV-2 proteases with an in silico approach. The samples were obtained from PubChem and RSCB PDB. Antivirus probability prediction was performed on PASS Online. Virtual screening was performed with PyRx via molecular docking. Visualization was used by PyMol and Discovery Studio. Compounds with the best antiviral potential are indicated by the low binding affinity value to the target proteins, namely SARS-CoV-2 TMPRSS2 and PLpro. The results showed that purslane luteolin has the best antiviral potential. However, further studies are required to validate this computational prediction. © 2022 Phcogj.Com.
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The global pandemic of COVID-19 has caused disastrous consequences for both humans and the economy. The purpose of this study was to determine the potential of juwet (Syzygium cumini L.) and moringa (Moringa oleifera L.) as inhibitors of RBD spike, helicase, Mpro, and RdRp activity of SARS-CoV-2 with an in-silico approach. Samples were obtained from PubChem and RSCB PDB databases. The drug similarity analysis was determined using Swiss ADME and the Lipinski rule of five. Prediction of antivirus probabilities is carried out with PASS Online. Molecular screening is performed by molecular docking using PyRx. Visualization was used using PyMol and Discovery Studio. The bioactive compounds with the best antiviral potential had the lowest affinity bonds to the target proteins against RBD spike, helicase, Mpro, and RdRp of SARS-CoV-2. Results show that ellagic acid from java plum and myricetin from moringa have the best potential as potential antivirals. However, more research is required to validate the results of these computational predictions.
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Global infection and mortality rates have soared to millions due to SARS-CoV-2 human-to-human transmission via droplets which then declared as pandemic. This study examined the created cold plasma equipment (CPE) effectiveness in reducing COVID-19 transmission in a confined space. CPE sucked air using a fan in a test chamber then pushed it into a cold plasma reactor. The results indicated that it was able to terminate all SARS-CoV-2 variants along with bacteria and fungi indoors by keeping it turned on for 30 min' minimum. CPE was proven as safe and effective to hinder virus transmission with the acceptable ozone emission as the side effect. © 2022 University of Kerbala.
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The world is endangered by the COVID‐19 pandemic caused by SARS‐CoV‐2, people are dying in thousands every day, and without an actual treatment, it seems that bringing this global health problem to a quit is impossible. Natural products have been in constant use since ancient times and are proven by time to be effective. Medicinal plants from Indonesia may lead to the discovery of the novel drugs. Mangosteen or Garcinia mangostana L. is a native tropical fruit from Southeast Asia and is known to contain bioactive compounds. Interestingly, the main xanthone derivatives are alpha-mangostin and gamma-mangostin, these compounds have a variety of pharmacological activities such as antiviral activity. In summary, this study showed potential pharmacological benefits of alpha-mangostin and gamma-mangostin isolated from mangosteen against SARS-CoV-2. Thus, mangosteen exhibits as a valuable plant and a candidate for future drug development to fight SARS-CoV-2. However, further trials, such as in vitro and in vivo evaluation, are needed to prove the validity of these findings.
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The global pandemic of coronavirus disease is still widely spread across the world causing catastrophic effect in both human life and global economy. By the end of year 2021, it has caused a total of 5.437.636 deaths across the world. Indonesia has rich plant biodiversity including medicinal plants that may be used for combating the virus. One of the commonly used medicinal plants comes from Allium species and it has been proved to have antiviral activity. Conducting an in silico study, we screened bioactive compounds that came from Allium sativum to fight against coronavirus through the inhibition of 3CL-Pro, one of the major protease that have an active role for viral replication. Molecular docking of compounds from Allium sativum to 3CL-Pro resulting in the discovery of 5 compounds that have the best binding affinity to 3CL-Pro, which are squalene, 1,4-dihydro-2,3-benzoxathiin 3-oxide, 1,2,3-propanetriyl ester, trans-13-octadecenoic acid and methyl-11-hexadecenoate with binding affinity of -7, -6.5, -5.9, -5.7 and -5.6 kcal/mol, respectively. It is very likely that these compounds can be candidates for therapeutic agents and these candidates need to be studied further.
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes COVID-19 which is responsible for respiratory illness infection in humans. The virus was first identified in China in 2019 and later spread to other countries worldwide. This study aims to identify the bioactive compounds from mangosteen (Garcinia mangostana L.) as an antiviral agent via dual inhibitor mechanisms against two SARS-CoV-2 proteases through the in silico approach. The three-dimensional structure of various bioactive compounds of mangosteen from the database was examined. Furthermore, all the target compounds were analyzed for drug, antiviral activity prediction, virtual screening, molecular interactions, and threedimensional structure visualization. It aimed to determine the potential of the bioactive compounds from mangosteen that can serve as antiviral agents to fight SARS-CoV-2. Results showed that the bioactive compounds from mangosteen have the prospective to provide antiviral agents that contradict the virus via dual inhibitory mechanisms. In summary, the binding of the various bioactive compounds from mangosteen results in low binding energy and is expected to have the ability to induce any activity of the target protein binding reaction. Therefore, it allows various bioactive compounds from mangosteen to act as dual inhibitory mechanisms for COVID-19 infection.
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Coronavirus disease (COVID-19), which was due to novel coronavirus was detected in December 2019 in Wuhan, China for the first time and spread rapidly became a global pandemic. This study aimed to predict the potential of macroalgae compounds as SARS-CoV-2 antiviral by inhibiting of ACE2 receptor through in silico approach. Twenty-seven macroalgae compounds were obtained from PubChem (NCBI, USA), while target protein ACE2 receptor was collected from Protein Data Bank (PDB). Then the initial screening study drug-likeness conducted by Lipinski rule of five web server and prediction of bioactive probability carried out by PASS (Prediction of activity spectra for biologically active substances) Online web server. After those compounds were approved by Lipinski's rule of five and PASS online prediction web server, the blind docking simulation was performed using PyRx 0.8 software to show binding energy value. Molecular interaction analysis was done using BIOVIA Discovery Studio 2016 v16.1.0 and PyMOL v2.4.1 software. There are six macroalgae compounds approved by Lipinski's rule of five and PASS Online Analysis. The result is that macroalgae compound siphonaxanthin among 27 macroalgae compound showed strong binding energy to bind ACE2 receptor with -8.8 kcal/mol. This study also used the SARS-CoV-2 drugs as positive control: remdesivir, molnupiravir, baricitinib, lopinavir, oseltamivir, and favipiravir. The result shows that siphonaxanthin has lowest binding energy than the common SARS-CoV-2 drug. Macroalgae compounds are predicted to have potential as SARS-CoV-2 antiviral. Thus, extension studies need to investigate by in vitro and in vivo analysis for confirmation the siphonaxanthin's inhibitory activity in combat SARS-CoV-2.
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Introduction: To date, no specific therapeutic drug has been approved to target SARS-CoV-2. Hence, it remains a major challenge to decide what potential therapeutic regimens to treat COVID-19 patients. This study aims to investigate curcumin and virgin coconut oil (VCO) effects on cytokine levels (IL-1β, IL-2, IL-6, IL-18, TNF-α, and IFN-β) in COVID-19 patients. Methods: This study was a single-center, controlled trial with a parallel Arm or a Randomized Clinical trial design. A total of sixty COVID-19 patients admitted to the Universitas Sebelas Maret Hospital, Surakarta, Indonesia, were divided into two groups. The first group, consisting of 30 patients, was treated with Azithromycin 500 mg + Oseltamivir 2×75 mg + Hydroxychloroquine 400 mg/day for 5 days. The second group, comprising 30 patients, was treated with Azithromycin 500 mg + Oseltamivir 2×75 mg + Hydroxychloroquine 400 mg/day for 5 days, added with VCO 30 mL and curcumin 3×1 g/day for 21 days. The cytokine profiles of the serum samples were analyzed by the enzyme-linked immunosorbent assay (ELISA) on days 1, 14, and 21. Results: Our study showed that the second group had a significant reduction in IL-1β, IL-2, IL-6, TNF-α, and IFN-β levels after being treated with standard therapy added with curcumin and VCO on day 21 (p<0.05). Conclusion: These results su ested that curcumin and VCO mi ht benefit the treatment of COVID-19 atients
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Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide pandemic. Ginger (Zingiber officinale) is a rhizome, which is commonly used for culinary and medicinal purposes. In Indonesia, ginger is taken as traditional medicine by processing it into a drink known as jamu. The present study aimed to assess and evaluate the bioactive compounds in ginger that can be used in drug design for treating COVID-19. The crystal structure of the SARS-CoV-2 main protease (M-pro) was generated from a protein sequence database, i.e., Protein Data Bank, and the bioactive compounds in ginger were derived from the existing compounds library. M-pro is involved in polyprotein synthesis, including viral maturation and nonstructural protein gluing, making it a potential antiviral target. Furthermore, the bioactive compounds in ginger were analyzed using Lipinski's rule of five to determine their drug-like molecular properties. Moreover, molecular docking analysis was conducted using the Python Prescription 0.8 (Virtual Screening Tool) software, and the interaction between SARS-CoV-2 M-pro and the bioactive compounds in ginger was extensively examined using the PyMOL software. Out all of the 16 bioactive compounds that were docked successfully, 4-gingerol, which has the lowest binding energy against SARS-CoV-2 M-pro, as per the virtual screening results, was proven to have the most potential as a viral inhibitor of SARS-CoV-2.
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A massive transmission of SARS-CoV-2, which happens particularly in developing countries has continuously triggered a COVID-19 tsunami and may genuinely increase the mortality number. The significant mortality rate caused by the SARS-CoV-2 pandemic has made it a major world problem. Viral infectivity could arise from the lack of information on the specific antiviral drug. Tamarindus indica has been proven to be a potential antiviral through in vivo research as it decreases viral load in animal viruses. Nevertheless, at the preliminary stage, evidence-based approach like in silico study is necessitated to evaluate its potential as an antiviral in humans. This study screened the content of the active compounds of Tamarindus indica and identified its potential as an antiviral toward SARS-CoV-2 through an entry inhibitor mechanism using bioinformatics tools. Sample retrieval was carried out in the database, then the sample was identified for drug-likeness on the server. Likewise, molecular docking and dynamic simulations were carried out on the identified bioactive compounds. The results showed that all the bioactive compounds possess drug-like molecules and β-sitosterol has the most negative binding affinity. Tamarindus indica is predicted to be an antiviral candidate for SARS-CoV-2 with an entry inhibitor mechanism through a compound, specifically called β-sitosterol.
ABSTRACT
In some cases, the immune system in COVID-19 patients leads to the release of excess cytokine production (cytokine storm), which will potentially develop into pneumonia. Interleukin 6 (IL-6) plays the role of pro-inflammatory cytokine, it is a receptor mediated signalling system. Macroalgae is well known as a source of valuable bioactive substances with potential biological activities. Among them is the sulphated polysaccharide lambda-carrageenan λ-CGN which has been reported as an anti-inflammatory agent. However, its mechanism of action against IL-6 production is currently unknown. This study aims to predict potential molecular mechanisms of λ-CGN chemical compound against IL-6 expression through in silico study. Chemical compound of λ-CGN and target protein in this study were obtained from the pubchem and protein data bank (PDB). The molecular docking prediction was conducted with PyRx software, the result is λ-CGN compound showing strong binding energy to bind target protein IL-6 receptor with the value of -5.9 kcal/mol. Based on the results of in silico study, the sulphated polysaccharide λ-CGN potentially inhibits IL-6R expression by binding ligand pocket with six conventional hydrogen bonds (amino acid residus: His256, His 257, Trp 219, Arg 231, and Asp 221) and two carbon hydrogen bonds (amino acid residus: THR 218 and GLN 220). Binding with these amino acid residues potentially contributes to IL-6 receptor structural change which could result in functional change. Hence, further studies related to in vitro and in vivo investigations would be interesting to further understand the inhibitory mechanism of λ-CGN against IL-6.
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Context: SARS-CoV-2, a member of family Coronaviridae and the causative agent of COVID-19, is a virus which is transmitted to human and other mammals. Aims: To analyze the B-cell epitope conserved region and viroinformatics-based study of the SARS-CoV-2 lineage from Indonesian B.1.1.7 isolates to invent a vaccine nominee for overcoming COVID-19. Methods: The sequences of seven Indonesian B.1.1.7 isolates, Wuhan-Hu- 1 isolate, and WIV04 isolate were extracted from the GISAID EpiCoV and GenBank, NCBI. MEGA X was employed to understand the transformations of amino acid in the S protein and to develop a molecular phylogenetic tree. The IEDB was implemented to reveal the linear B-cell epitopes. In addition, PEP-FOLD3 web server was utilized to perform peptide modeling, while docking was performed using PatchDock, FireDock, and the PyMOL software. Moreover, in silico cloning was developed by using SnapGene v.3.2.1 software. Results: In this study, the changes of amino acid in all seven Indonesian B.1.1.7 isolates were uncovered. Furthermore, various peptides based on the B-cell epitope prediction, allergenicity prediction, toxicity prediction from S protein to generate a vaccine contrary to SARS-CoV-2 were identified. Furthermore, the development of in silico cloning using pET plasmid was successfully achieved. Conclusions: This study exhibits the transformations of amino acid in Indonesian B.1.1.7 isolates, and proposes four peptides ("LTPGDSSSGWTAG", "VRQIAPGQTGKIAD", "ILPDPSKPSKRS", and "KNHTSPDVDLG") from S protein as the candidate for a peptide-based vaccine. However, further advance trials such as in vitro and in vivo testing are involved for validation.
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Recently, the world is facing outbreaks of severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2 and the number of infected patients is increasing every day. Researchers are doing their best to find the most effective treatment to tackle this deathly virus. Several approaches had been proposed to be tested in the lab for efficacy but none of them are qualified to be used as the treatment of the COVID-19. Therefore, this study aimed to design a vaccine based on epitope, which was obtained from the nucleocapsid phosphoprotein (N protein). 38 samples of SARS-CoV-2 isolates were retrieved from the GISAID Database and NCBI GenBank. These samples were used to check the evolutionary relationship of the SARS-CoV-2 and determine whether these nucleocapsid proteins are well-conserved with less or even no mutations occur at all, and whether there was any evolutionary relationship between the recent coronavirus with the previous coronavirus by conducting the phylogenetic analysis. Then, it is desirable to see the molecular interaction between the human BCR/FAB receptor with the predicted peptides through the molecular docking process. All of the peptides were generated by the IEDB analysis tools and have already been tested for antigenicity, so the one that was being docked is the peptide that has antigen properties. Based on the analysis that had been done, the PEP1 was recommended as an epitope-based peptide vaccine candidate to deal with the SARS-CoV-2 outbreaks. Copyright © 2020 THE AUTHOR(S).
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Context: The COVID-19 outbreak is caused by the transmission and infection of SARS-CoV-2 at the end of 2019. It has led many countries to implement lockdown policies to prevent the viral spreading. Problems arise in a COVID-19 patient because of viral infection that leads to a systemic response in the immune system, specifically due to cytokine storm. Moreover, the antiviral drugs that have not been found. Indonesia had a variety of traditional medicines, such as is 'jamu'. It consists of a mixture of natural ingredients such as Moringa oleifera Lam. and Curcuma longa L. Aims: To identify the activity of dual inhibitors as antiviral and anti-inflammatory agents from herbal combination compounds. Methods: Sample was collected from PubChem (NCBI, USA) and Protein Data Bank (PDB), then drug-likeness analysis using Lipinski rule of five in SCFBIO web server and bioactive probability analysis of bioactive compounds were conducted by PASS web server. Furthermore, the blind docking method was performed using PyRx 0.8 software to determine the binding activity and molecular interaction by PoseView web server and PyMol software v2.4.1 (Schrodinger, Inc, USA). Results: Cryptochlorogenic acid and curcumin have been computationally proven as dual inhibitors for antivirals by inhibiting Mpro SARS-CoV-2 and as anti-inflammatory through inhibition of NFKB1 activity. However, the results are merely computational so that it must be validated through a wet lab research. Conclusions: The combination of Moringa oleifera Lam. and Curcuma longa L. is predicted to have antiviral and anti-inflammatory activity through dual inhibitor mechanism played by cryptochlorogenic acid and curcumin.