ABSTRACT
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the virus that causes Coronavirus 2019 (COVID-19). To date, there has been no proven effective drug for the treatment or prevention of COVID-19. A study on developing inhibitors for this virus is carried out using molecular docking simulation methods. 3CL-Pro, PL-Pro, Helicase, N, E, and M protein were used as protein targets. Autodock Vina, Autodock 4.2, and PSOVina were used in this study. This study aims to obtain a model of ligands interactions of active natural compounds against the receptor protein encoded by the SARS-CoV-2 genome and their free binding energy to propose active compounds from natural products that have potential as a drug for COVID-19. Corilagin (-14,42 kcal/mol), Scutellarein 7-rutinoside (-13,2 kcal/mol), Genistein 7-O-glucuronide (-10,52 kcal/mol), Biflavonoid-flavone base + 3O (-11,88 and-9,61 kcal/mol), and Enoxolone (-6,96 kcal/mol) has the best free energy value at each protein target indicating that the compound has the potential as a viral protein inhibitor for further investigation. This research is limited to computer simulations, where the results obtained are still a prediction. © 2023, Universitas Jenderal Soedirman. All rights reserved.
ABSTRACT
Research related to SARS-CoV-2 drugs is still ongoing. In this initial research, we perform a computational approach on SARS-CoV-2 inhibitors. RNA-dependent RNA polymerase (RdRp) is one of the functional proteins in SARS-CoV-2 that can be a target for drug development, which has an essential function in the viral replication process synthesizing the RNA genome of the virus. This study used the RdRp-Remdesivir complex structure from RCSB with ID PDB 7BV2, with a resolution of 2.5 Å. Currently, Remdesivir is under the clinical trial phase as a Covid-19 drug. In this study, we tested a thousand natural Indonesian compounds used as SARS-CoV-2 RdRp inhibitors obtained from the Indonesian natural compounds database (HerbalDB). The first stage of this computational analysis was pharmacophore modeling structure-based drug design. The natural compounds were analyzed based on their steric and electronic similarities to Remdesivir. A molecular docking simulation was then performed to obtain binding energy and bond stability to produce natural compounds that can inhibit RdRp SARS-CoV-2. The final stage was the molecular dynamics simulation that explored the conformational space of natural compounds and proteins. The ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) test was carried out on the five best compounds to obtain these natural compounds' computational pharmacology and pharmacokinetics. The simulation identified Sotetsuflavone (CID: 5494868) from Cycas revoluta, Grossamide (CID: 5322012) from Cannabis sativa, and 6-Hydroxyluteolin-6,7-disulfate (CID: 13845917) from Lippia nodiflora are the best compounds that can inhibit RdRp SARS-CoV-2. These potential compounds can then be tested in-vitro and in-vivo in the future. © 2022, Universitas Jenderal Soedirman. All rights reserved.
ABSTRACT
Inflammatory diseases are diseases characterized by inflammatory symptoms. Acute inflammatory disease can cause dysregulation of the inflammatory immune response, thereby inhibiting the development of protective immunity against infection. Among the acute inflammatory disease is COVID-19. The initial viral infection causes the antigen-presenting cells to detect the virus through a phagocytosis mechanism in the form of macrophage and dendritic cells. Lactobacillus fermentum and L. plantarum are gram-positive bacteria potentially serving as immunomodulators caused by inflammation and immune system response. Short-chain fatty acids (SCFA) produced by Lactobacillus can induce immune response through tolerogenic dendritic cells. This probiotic bacterium can induce the production of different cytokines or chemokines. Following the results of in vitro and in vivo tests, L. fermentum and L. plantarum can induce IL-10 release to activate regulatory T-cell and inhibit tumor necrosis factor-alpha (TNF-alpha) binding activity of nuclear factor kappa B (NF-kappaB). Literature review showed that dysregulation of inflammatory immune response disorders due to inflammatory disease could be treated using probiotic bacteria L. fermentum and L. plantarum. Therefore, it is necessary to conduct further studies on the potential of indigenous Indonesian strains of these two bacteria as anti-inflammatory and immunostimulants. Copyright © 2022 Harry Noviardi, Dyah Iswantini, Sri Mulijani, Setyanto Tri Wahyudi, Tatik Khusniati. Published by Institute for Research and Community Services Universitas Muhammadiyah Palangkaraya. This is an Open Access article under the CC-BY-SA License (http://creativecommons.org/licenses/by-sa/4.0/)
ABSTRACT
Kaurene diterpenoids were found in some plants such as Adenostemma lavenia and Pteris semipinnata to have antioxidant, antiinflammatory, anticancer, antitumor, cytotoxic, and antiviral activities. To evaluate the potency of kaurene diterpenoids as antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we conducted an in silico study of several kaurene diterpenoids and antiviral drugs such as remdesivir and favipiravir in inhibition essential SARS-CoV-2 proteins including 3CLpro, Plpro, nucleocapsid (N), and membrane (M) through molecular docking, molecular dynamic (MD) simulations, adsorption, distribution, metabolism, excretion, and toxicity (ADMET), and pharmacokinetic properties prediction using a number of pieces of software. The docking study showed that the kaurene diterpene glycosides have a higher binding affinity to the 3CLpro, N, and M proteins of SARS-CoV-2 than other kaurene diterpenoids and even antiviral drugs such as remdesivir and favipiravir. Inhibition of these nonstructural and structural proteins has a significant impact on disrupting the viral replication and viral assembly of SARS-CoV-2. Almost all the complexes showed minimum deviation and fluctuation, indicating that each ligand is strongly bound to the binding site of proteins. ADMET prediction revealed all kaurene diterpenoids were well absorbed by the human intestine, noncarcinogenic, and did not cause mutations in DNA. Therefore, we expected these materials could be a potential preventive and therapeutic agent in the fight against the COVID-19 disease. © 2022. Nurlela Nurlela et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License
ABSTRACT
The Covid-19 pandemic has undermined the achievements of economic growth in various countries, including in the Southeast Asia region. The characteristics of the Southeast Asian region, which are based on the agricultural and industrial sectors, have become the foundation for economic recovery efforts. Therefore, this study chose the agricultural and industrial sectors as the database of research. Further, this study aims to analyze the influence of the agricultural sector and the industrial sector on economic growth in ASEAN+6, covering Indonesia, Thailand, Vietnam, Malaysia, the Philippines, and Singapore. In this study, secondary data will be used for the period from 1991 to 2020 and the sources is from the official website of the World Bank by taking world development indicator data with the Generalized Method of Moment (GMM) method. It was found that the share of value-added in the agricultural sector and the industrial sector in the ASEAN+6 has a significant contribution to economic recovery efforts in the region. The increase in these two sectors has shown a real impact on accelerating economic recovery through increased production activity. The findings of this study are expected to be a reference for policies to increase output in the two sectors, encourage economic growth, and accelerate economic recovery in each country. © 2021 Ascociacion Internacional de Economia Aplicada. All Rights Reserved.
ABSTRACT
This study examines the volatility of inflation in Indonesia before and during COVID-19, focusing on people’s purchasing power. The high inflation variability makes future price expectations uncertain, creating risks in the long run and uncertainty in wealth redistribution. The ARIMA model was used from January 2005 to June 2020. The results show that the ARMA (0.1) model is suitable for testing inflation volatility in Indonesia. Forecasting results show that inflation for the next six months will still be under pressure due to COVID-19. © 2022 by Emerald Publishing Limited.
ABSTRACT
The novel coronavirus disease 19 (Covid-19) which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a pandemic across the world, which necessitate the need for the antiviral drug discovery. One of the potential protein targets for coronavirus treatment is RNA-dependent RNA polymerase. It is the key enzyme in the viral replication machinery, and it does not exist in human beings, therefore its targeting has been considered as a strategic approach. Here we describe the identification of potential hits from Indonesian Herbal and ZINC databases. The pharmacophore modeling was employed followed by molecular docking and dynamics simulation for 40 ns. 151 and 14480 hit molecules were retrieved from Indonesian herbal and ZINC databases, respectively. Three hits that were selected based on the structural analysis were stable during 40 ns, while binding energy prediction further implied that ZINC1529045114, ZINC169730811, and 9-Ribosyl-trans-zeatin had tighter binding affinities compared to Remdesivir. The ZINC169730811 had the strongest affinity toward RdRp compared to the other two hits including Remdesivir and its binding was corroborated by electrostatic, van der Waals, and nonpolar contribution for solvation energies. The present study offers three hits showing tighter binding to RdRp based on MM-PBSA binding energy prediction for further experimental verification. © 2020, Gadjah Mada University. All rights reserved.