Natural Compound against COVID-19 in Silico Screening by Attacking Mpro and ACE2 Using Molecular Docking (original) (raw)
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MOLECULAR DOCKING STUDY OF NATURALLY OCCURRING COMPOUNDS AS INHIBITORS OF COVID-19
Asian Journal of Pharmaceutical and Clinical Research, 2021
The worldwide spread of COVID-19 is an emergent issue to be tackled. Currently, several works in various fields have been made in rather short periods. The present study aimed to assess bioactive compounds found in medicinal plants as potential COVID-19 M pro inhibitors using molecular docking study. The docking analyses were performed using Autodock, Discovery Studio Visualiser and Igemdock. The binding energy obtained from the docking of 6LU7 with native ligand cupressuflavone is-8.9 kcal/mol. These findings will provide the opportunities to identify the right drug to combat COVID-19.
Molecular Docking Studies on Synthetic Therapeutic Agents for COVID-19
Chemistry proceedings, 2020
Coronavirus disease (COVID-19) is an infectious disease caused by coronavirus 2 (SARS-CoV-2) which was detected for the first time in Wuhan China in December 2019. The rapid spread of this highly contagious and pathogenic virus led to the declaration of the pandemic by the World Health Organization (WHO) on March 11, 2020. In these conditions, the discovery of new antiviral agents is extremely important. For the development of the anti-SARS-CoV-2 drugs, the fastest way is to find potential molecules from the marketed drugs by molecular docking studies.
Natural products as inhibitors of COVID-19 main protease – A virtual screening by molecular docking
Pharmaceutical Sciences, 2021
Background: The novel coronavirus (2019-nCoV) causes a severe respiratory illness unknown to a human before. Its alarmingly quick transmission to many countries across the world has resulted in a global health emergency. Therefore, an imminent need for drugs to combat this disease has been increased. Worldwide collaborative efforts from scientists are underway to determine a therapy to treat COVID-19 infections and reduce mortality rates. Since herbal medicines and purified natural products have been reported to have antiviral activity against Coronaviruses (CoVs), this in silico evaluation was performed for identifying potential natural compounds with promising inhibitory activities against COVID-19. Methods: In this study, a High Throughput Virtual Screening (HTVS) protocol was used as a fast method for discovering novel drug candidates as potential COVID-19 main protease (M pro) inhibitors. Over 180,000 natural product-based compounds were obtained from the ZINC database and virtually screened against the COVID-19 M pro. In this study, the Glide docking program was applied for high throughput virtual screening. Also, Extra precision (XP) has been used following the induced-fit docking (IFD) approach. The ADME properties of all compounds were analyzed and a final selection was made based on the Lipinski rule of five. Also, molecular dynamics (MD) simulations were conducted for a virtual complex of the best scoring compound with COVID-19 protease. Results: Nineteen compounds were introduced as new potential inhibitors. Compound ZINC08765174 (1-[3-(1H-indol-3-yl) propanoyl]-N-(4-phenylbutan-2-yl)piperidine-3carboxamide showed a strong binding affinity (-11.5 kcal/mol) to the COVID-19 M pro comparing to peramivir (-9.8 kcal/mol) as a positive control.
Investigation of antiviral substances in Covid 19 by Molecular Docking: In Silico Study
African Health Sciences
Aims: This paper aimed to investigate the antiviral drugs against Sars-Cov-2 main protease (MPro) using in silico methods. Material and Method: A search was made for antiviral drugs in the PubChem database and antiviral drugs such as Bictegravir, Emtricitabine, Entecavir, Lamivudine, Tenofovir, Favipiravir, Hydroxychloroquine, Lopinavir, Oseltamavir, Remdevisir, Ribavirin, Ritonavir were included in our study. The protein structure of Sars-Cov-2 Mpro (PDB ID: 6LU7) was taken from the Protein Data Bank (www.rcsb. Org) system and included in our study. Molecular docking was performed using AutoDock/Vina, a computational docking program. Protein-ligand interactions were performed with the AutoDock Vina program. 3D visualizations were made with the Discovery Studio 2020 program. N3 inhibitor method was used for our validation. Results: In the present study, bictegravir, remdevisir and lopinavir compounds in the Sars-Cov-2 Mpro structure showed higher binding affinity compared to the ant...
Screening of potential inhibitors of COVID-19 with repurposing approach via molecular docking
Network Modeling Analysis in Health Informatics and Bioinformatics
SARS-CoV-2 (COVID-19) is the causative organism for a pandemic disease with a high rate of infectivity and mortality. In this study, we aimed to assess the affinity between several available small molecule and proteins, including Abl kinase inhibitors, Janus kinase inhibitor, dipeptidyl peptidase 4 inhibitors, RNA-dependent RNA polymerase inhibitors, and Papainlike protease inhibitors, using binding simulation, to test whether they may be effective in inhibiting COVID-19 infection through several mechanisms. The efficiency of inhibitors was evaluated based on docking scores using AutoDock Vina software. Strong ligand-protein interactions were predicted among some of these drugs, that included: Imatinib, Remdesivir, and Telaprevir, and this may render these compounds promising candidates. Some candidate drugs might be efficient in disease control as potential inhibitors or lead compounds against the SARS-CoV-2. It is also worth highlighting the powerful immunomodulatory role of other drugs, such as Abivertinib that inhibits pro-inflammatory cytokine production associated with cytokine release syndrome (CRS) and the progression of COVID-19 infection. The potential role of other Abl kinase inhibitors, including Imatinib in reducing SARS-CoV and MERS-CoV viral titers, immune regulatory function and the development of acute respiratory distress syndrome (ARDS), indicate that this drug may be useful for COVID-19, as the SARS-CoV-2 genome is similar to SARS-CoV.
Repurposing the inhibitors of COVID-19 key proteins through molecular docking approach
Process Biochemistry, 2021
The severe acute respiratory syndrome coronavirus 2, famous as COVID-19, has recently emerged as a novel virus and imposed an unrecoverable loss to global health and the economy. At present, no effective drug against COVID-19 is available and currently available viral drugs targeting the viral key proteins of related RNA viruses have been found ineffective against COVID-19. This study evaluated the inhibitors of the viral proteases and other structural proteins, including Mpro (Main protease), RdRp (RNA-dependent RNA polymerase), and spike glycoprotein from synthetic and herbal sources. The molecular docking-based approach was used to identify and evaluate the putative inhibitors of key proteins involved in viral replication and survival. Furthermore, the pharmaceutical properties of these inhibitors were explored to predict the drug suitability as a therapeutic agent against COVID-19 by considering adsorption, distribution, metabolism, and excretion (ADME) using Lipinski's rule or SwissADME. Trandolapril, Benazepril, and Moexipril were evaluated as the best non-carcinogenic and non-toxic potential inhibitors of spike glycoprotein, Mpro, and RdRp, respectively. The drugs showed significant binding affinities against the active sites of respective SARS_CoV-2 target proteins; hence, they can be used as potential therapeutic agents for the treatment of COVID-19.
Synthesis and molecular docking study of novel COVID-19 inhibitors
Turkish Journal of Chemistry, 2021
Introduction The most interested subject in 2020 is corona virus disease, which was named as COVID-19 by the WHO (World Health Organization) on the February 11, 2020 [1], This novel coronavirus is called as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by the international virus classification commission. Viruses in the corona family cause diseases in respiratory, gastrointestinal, hepatic, and central nervous system in both humans and animals [2]. Due to the respiratory transmission of SARS-CoV-2 from person to person, it has led to the formation of pandemic conditions in a short time. The world has become familiar with corona virus first with SARS (Severe Acute Respiratory Syndrome) epidemic, and then with the MERS (Middle East Respiratory Syndrome) epidemic [3]. The cause of pneumonia in COVID-19 cases is revealed as unique b-CoV strain [4]. The scientific world does not have an approved treatment specific to SARS-CoV-2. Luckily, it was shown that the novel b-CoV shows 88% similarity to the (SARS)-like coronaviruses, and about 50% to the MERS CoV. Therefore, drugs used for SARS and MERS have come forth again [5]. There are many potential drug candidates for the treatment of COVID-19 such as, oseltamivir [2], lopinavir/ ritonavir [6, 7], nucleoside analogues and nucleotide inhibitors [8] remdesivir [6, 9], tenofovir, ribavirin, sofosbuvir, galidesivir [10] antibiotics [11] and chloroquine and hydroxychloroquine [12,13]. Alternatively, various phytochemicals were used against SARS-CoV-2 virus too. Examples are, belachinal, macaflavanone E and vibsanol B [14], flavone and coumarine derivatives [15], saikosaponins [16], crocin, digitoxigenin, and ß-eudesmol [17], d-viniferin, myricitrin, Taiwan homoflavone A, lactucopicrin 15-oxalate, nymfolide A, afzelin, biorobin, hesperidin and phyllaemblicin B [18], and theophylline derivatives [19]. Hydroxychloroquine, which is mainly used for the treatment of malaria [20] was the first drug to be considered suitable for use in the treatment of COVID-19. On 17 June 2020, WHO announced that the research examining the effects of hydroxychloroquine in the treatment of COVID-19 was cancelled. It has been reported that the drug does not have a positive effect on the mortality rate and duration of hospital stay compared to standard treatments [21]. On July 1, 2020 FDA (Food and Drug Administration) issued a warning stating that hydroxychloroquine causes heart rhythm problems, blood and lymph system disorders, kidney injuries, and liver problems and failure [22]. Remdesivir is an antiviral drug that block viral RNA synthesis of RNA viruses such as SARS and MERS. The antiviral efficacy of the drug has been proven in many in vitro studies [23, 24]. However, it has not been approved for the COVID-19 treatment yet. As the emergency situation continues, FDA has issued an authorization on the use of the drug on hospitalized patients receiving COVID-19 treatment [22].
Journal of King Saud University - Science, 2021
Coronavirus disease (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Up to date, there has been no specific cure to treat the disease. Indonesia is one of the countries that is still fighting to control virus transmission. Yet, at the same time, Indonesia has a rich biodiversity of natural medicinal products that potentially become an alternative cure. Thus, this study examined the potency of a natural medicinal product, Sulawesi propolis compounds produced by Tetragonula sapiens, inhibiting angiotensin-converting activity enzyme-2 (ACE-2), a receptor of SARS-CoV-2 in the human body. In this study, molecular docking was done to analyze the docking scores as the representation of binding affinity and the interaction profiles of propolis compounds toward ACE-2. The results illustrated that by considering the docking score and the presence of interaction with targeted sites, five compounds, namely glyasperin A, broussoflavonol F, sulabiroins A, (2S)-5,7-dihydroxy-4 0-methoxy-8-prenylflavanone and isorhamnetin are potential to inhibit the binding of ACE-2 and SARS-CoV-2, with the docking score of À10.8, À9.9, À9.5, À9.3 and À9.2 kcal/mol respectively. The docking scores are considered to be more favorable compared to MLN-4760 as a potent inhibitor.
Avicenna Journal of Medical Biochemistry
Background: Coronavirus disease 2019 (COVID-19) as a serious global health crisis leads to high mortality and morbidity. However, currently, there are no effective vaccines and treatments for COVID-19. Main protease (Mpro) and angiotensin-converting enzyme 2 (ACE2) are the best therapeutic targets of COVID-19. Objectives: The main purpose of this study is to investigate the most appropriate drug and candidate compound for proper interaction with Mpro and ACE2 to inhibit the activity of COVID-19. Methods: In this study, repurposing of approved drugs and screening of candidate compounds using molecular docking and fragment-based QSAR method were performed to discover the potential inhibitors of Mpro and ACE2. QSAR and docking calculations were performed based on the prediction of the inhibitory activities of 5-hydroxy indanone derivatives. Based on the results, an optimal structure was proposed to inhibit the activity of COVID-19. Results: Among 2629 DrugBank approved drugs, 118 were ...
VirusDisease, 2021
With the recent pandemic outbreak and subsequent worldwide spread of COVID-19 from Wuhan city of China, millions of infections and lakhs of deaths have resulted. No registered therapies have been developed to treat infection with COVID-19. The present study was conducted to evaluate the efficacy of herbal drugs as drug target molecules against COVID-19 by molecular docking. The inhibitory effects of natural compounds were analyzed against COVID-19 main protease (M pro). The inhibition of M pro prevents the virus replication. In the current study forty eight compounds were screened with AutoDock 4.2. Discovery Studio has visualised the interaction between targeted protein amino acids and ligands. The potent phytochemicals inhibitors were identified based on the binding energy with the targeted protein. Phytochemicals such as Fagaronine, Isoboldine, Sageone, Lycorine and Wogonin were noted as potential inhibitors whereas the docking study demonstrated the significant binding energy with the target enzyme, viz.-6.21,-5.99,-5.97,-5.86 and-5.62 Kcal / Mol respectively. These lead compounds can be used against SARS-CoV-2 infections for drug development.