Natural Compound against COVID-19 in Silico Screening by Attacking Mpro and ACE2 Using Molecular Docking (original) (raw)
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.
Recently, a new and fatal strain of coronavirus named as SARS-CoV-2 (Disease: appeared in Wuhan, China in December of 2019. Due to its fast growing human to human transmission and confirmed cases in nearly every country, it has been declared as pandemic by World Health Organisation (WHO) on 11 March 2020. Till now, there is no therapy such as vaccines and specific therapeutic agents available globally. Inspite of this, some protease inhibitors and antiviral agents namely lopinavir, ritonavir, remdisivir and chloroquine are under investigation and also implemented in several countries as therapeutic agents for the treatment of COVID-19. Seeing the health crisis across the world, it was our aim to find out a suitable drug candidate which could target SARS-CoV-2. For this purpose, molecular docking of 7 proteinsof SARS-CoV-2 was done with 18active constituents that have previously been reported to be antiviral or anti-SARS-CoV agents. The docking results of these 18 compounds were compared with 2 FDA approved drugs that have are currently being used in COVID 19, namely Remdesivir and Chloroquine. Our result revealed that among all, epigallocatechin gallate (EGCG), a major constituent of green tea, is the lead compound that could fit well into the binding sites of docked proteins of SARS-CoV-2. EGCG showed very strong molecular interactions with binding energies -9.30, -8.66, -8.38, -7.57, -7.26, -6.99 and -4.90 kcal/mole for6y2e, 6vw1, 6vww, 6lxt,6vsb, 6lu7 and 6lvnproteins of SARS-CoV-2, respectively.Therefore, EGCG as per our results, should be explored as a drug candidate for the treatment of COVID-19.
The Suggestion of a Drug for COVID-19 with Molecular Docking Original Article
Medical Laboratory Journal, 2023
Background and objectives: This study aimed to study the interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein complex and seven drugs that inhibit the angiotensin-converting enzyme 2. Methods: Plots of protein-ligand interaction were obtained using the LigPlot software. In addition, binding energies in kcal/mol, hydrophobic interactions, and hydrogen bonds were determined. Autodock software v.1.5.6 and AutoDock Vina were used for the analysis of molecular docking processes. Results: The only structure that interacted with the SARS-CoV-2 spike protein was anakinra. Conclusion: Anakinra was the only drug that interacted with the SARS-CoV-2 spike protein. This could be further investigated for finding a temporary alternative medicine for the treatment of coronavirus disease 2019.
Journal of Biomolecular Structure and Dynamics
A new strain of coronavirus (CoV) has been identified as SARS-CoV-2, which is responsible for the recent COVID-19 pandemic. Currently, there is no approved vaccine or drug available to combat the pandemic. COVID-19 main protease (M pro) is a key CoV enzyme, which plays an important role in triggering viral replication and transcription, turns it into an attractive target. Therefore, we aim to screen natural products library to find out potential COVID-19 M pro inhibitors. Plant-based natural compounds from Sigma-Aldrich plant profiler chemical library have been screened through virtual molecular docking and molecular dynamics simulation to identify potential inhibitors of COVID M pro. Our virtual molecular docking results have shown that there are twenty-eight natural compounds with a greater binding affinity toward the COVID-19 M pro inhibition site as compared to the co-crystal native ligand Inhibitor N3 (-7.9 kcal/mol). Also, molecular dynamics simulation results have confirmed that Peonidin 3-O-glucoside, Kaempferol 3-Ob-rutinoside, 4-(3,4-Dihydroxyphenyl)-7-methoxy-5-[(6-O-b-D-xylopyranosyl-b-D-glucopyranosyl)oxy]-2H-1benzopyran-2-one, Quercetin-3-D-xyloside, and Quercetin 3-O-a-L-arabinopyranoside (selected based on the docking score) possess a significant amount of dynamic properties such as stability, flexibility and binding energy. Our In silco results suggests that all the above mention natural compounds have the potential to be developed as a COVID-19 M pro inhibitor. But before that, it must go through under the proper preclinical and clinical trials for further scientific validation.
Internation Journal of Evergreen Scientific Research, 2021
The pandemic COVID-19 resulted from the infection of the severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) has become the most emergent global health issue. Particular and efficient antiviral therapy against SARS-Cov-2 is still lacking, so the refinement of effective antiviral drugs against the virus is urgently needed. The phytochemical Zeylanone (D) extracted from Plumbago zeylanica has strong antiviral activity with other pharmacological effects. SARS-Cov-2 affects the individual host cell because of its strong binding affinity with ACE2 of the lung's epithelial cells by which the virus enters the host cell. Zeylanone contains a great inhibitory effects against the virus due to its attaching affinity with the same receptor (ACE2). The aim of this study is to design better conformer due to the adequate potency and suitable pharmacokinetics of Zeylanone. We have designed several derivatives and docked them against potential targets such as ACE2 (PDB ID: 6M0J), the main protease (PDB ID: 6LU7), RNA dependent RNA polymerase (PDB ID: 7BTF) and PLpro (PDB ID: 7KOL) crystal structures of proteins collected from the RCSB PDB protein data bank. AutoDockVina was used for docking, and drug-likeness, toxicity, carcinogenicity as well as pharmacokinetic properties were evaluated using PreADMET, SwissDrugDesign, and the admetSAR@LMMD online database. The interaction site between drugs and proteins, pocket size, type and distance of non-bond interaction were assessed by PyMOL and Discovery Studio visualizer v4.5.0.15071. Finally, all of the compounds were optimized, and their thermodynamic data were computed using Gauss View (v5.0). According to our findings, the derivative D3 has the highest binding value of-10.1 kcal/mol against 6M0J (ACE2), while the parent drug has a binding value of-8.9 kcal/mol against the same target. The derived drugs formed drugprotein complexes with various non-bond interactions for example conventional hydrogen bonds, alkyl bonds, pi-alkyl bonds, and pi-pi T-shaped bonds. All the derivatives ensured us of their non-toxicity and better pharmacokinetics than the parent drug. According to our investigation results, D3 (derived drug) can be referred to as a prospective novel inhibitor against ACE2 for the maintenance and treatment of viral affected patients.