An Investigation into the Identification of Potential Inhibitors of SARS-CoV-2 Main Protease Using Molecular Docking Study

2020 ◽  
Author(s):  
Sourav Das ◽  
Sharat Sarmah ◽  
Sona Lyndem ◽  
Atanu Singha Roy
Keyword(s):  
Clinical Trials ◽  
Molecular Docking ◽  
Active Site ◽  
Natural Compound ◽  
World Health ◽  
Molecular Docking Study ◽  
Control Drug ◽  
Main Protease

A new strain of a novel infectious disease affecting millions of people, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently been declared as a pandemic by the World Health Organization (WHO). Currently, several clinical trials are underway to identify specific drugs for the treatment of this novel virus. The inhibition of the SARS-CoV-2 main protease is necessary for the blockage of the viral replication. Here, in this study, we have utilized a blind molecular docking approach to identify the possible inhibitors of the SARS-CoV-2 main protease, by screening a total of 33 molecules which includes natural products, anti-virals, anti-fungals, anti-nematodes and anti-protozoals. All the studied molecules could bind to the active site of the SARS-CoV-2 protease (PDB: 6Y84), out of which rutin (a natural compound) has the highest inhibitor efficiency among the 33 molecules studied, followed by ritonavir (control drug), emetine (anti-protozoal), hesperidin (a natural compound), lopinavir (control drug) and indinavir (anti-viral drug). All the molecules, studied out here could bind near the crucial catalytic residues, HIS41 and CYS145 of the main protease, and the molecules were surrounded by other active site residues like MET49, GLY143, HIS163, HIS164, GLU166, PRO168, and GLN189. As this study is based on molecular docking, hence being particular about the results obtained, requires extensive wet-lab experimentation and clinical trials under <i>in vitro</i> as well as <i>in vivo </i>conditions.

An Investigation into the Identification of Potential Inhibitors of SARS-CoV-2 Main Protease Using Molecular Docking Study

2020 ◽  
Author(s):  
Sourav Das ◽  
Sharat Sarmah ◽  
Sona Lyndem ◽  
Atanu Singha Roy
Keyword(s):  
Clinical Trials ◽  
Molecular Docking ◽  
Active Site ◽  
Natural Compound ◽  
World Health ◽  
Molecular Docking Study ◽  
Control Drug ◽  
Main Protease

A new strain of a novel infectious disease affecting millions of people, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently been declared as a pandemic by the World Health Organization (WHO). Currently, several clinical trials are underway to identify specific drugs for the treatment of this novel virus. The inhibition of the SARS-CoV-2 main protease is necessary for the blockage of the viral replication. Here, in this study, we have utilized a blind molecular docking approach to identify the possible inhibitors of the SARS-CoV-2 main protease, by screening a total of 33 molecules which includes natural products, anti-virals, anti-fungals, anti-nematodes and anti-protozoals. All the studied molecules could bind to the active site of the SARS-CoV-2 protease (PDB: 6Y84), out of which rutin (a natural compound) has the highest inhibitor efficiency among the 33 molecules studied, followed by ritonavir (control drug), emetine (anti-protozoal), hesperidin (a natural compound), lopinavir (control drug) and indinavir (anti-viral drug). All the molecules, studied out here could bind near the crucial catalytic residues, HIS41 and CYS145 of the main protease, and the molecules were surrounded by other active site residues like MET49, GLY143, HIS163, HIS164, GLU166, PRO168, and GLN189. As this study is based on molecular docking, hence being particular about the results obtained, requires extensive wet-lab experimentation and clinical trials under <i>in vitro</i> as well as <i>in vivo </i>conditions.

scholarly journals Identification of Potent Inhibitors of COVID-19 Main Protease Enzyme by Molecular Docking Study

2020 ◽  
Author(s):  
pooja singh ◽  
Angkita Sharma ◽  
Shoma Paul Nandi
Keyword(s):  
Molecular Docking ◽  
Antiviral Drug ◽  
Cyclopiazonic Acid ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Docking Score ◽  
Protease Enzyme ◽  
Main Protease

<p>Within the span of a few months, the severe acute respiratory syndrome coronavirus, COVID-19 (SARS-CoV-2), has proven to be a pandemic, affecting the world at an exponential rate. It is extremely pathogenic and causes communicable infection in humans. Viral infection causes difficulties in breathing, sore throat, cough, high fever, muscle pain, diarrhea, dyspnea, and may lead to death. Finding a proper drug and vaccines against this virus is the need of the hour. The RNA genome of COVID19 codes for the main protease M<sup>pro</sup>, which is required for viral multiplication. To identify possible antiviral drug(s), we performed molecular docking studies. Our screen identified ten biomolecules naturally present in <i>Aspergillus flavus</i> and <i>Aspergillus oryzae</i> fungi. These molecules include Aspirochlorine, Aflatoxin B1, Alpha-Cyclopiazonic acid, Sporogen, Asperfuran, Aspergillomarasmine A, Maltoryzine, Kojic acid, Aflatrem and Ethyl 3-nitropropionic acid, arranged in the descending order of their docking score. Aspirochlorine exhibited the docking score of – 7.18 Kcal/mole, higher than presently used drug Chloroquine (-6.2930522 Kcal/mol) and out of ten ligands studied four has docking score higher than chloroquine. These natural bioactive compounds could be tested for their ability to inhibit viral growth <i>in- vitro</i> and <i>in-vivo</i>.<b> </b></p>

Potential Bioactive glycosylated flavonoids as SARS-CoV-2 Main protease Inhibitors: A molecular Docking Study

2020 ◽  
Author(s):  
sabri ahmed cherrak ◽  
merzouk hafida ◽  
mokhtari soulimane nassima
Keyword(s):  
Molecular Docking ◽  
Data Bank ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Chemical Structures ◽  
In Vivo Experiments ◽  
Main Protease

A novel (COVID-19) responsible of acute respiratory infection closely related to SARS-CoV has recently emerged. So far there is no consensus for drug treatment to stop the spread of the virus. Discovery of a drug that would limit the virus expansion is one of the biggest challenges faced by the humanity in the last decades. In this perspective, testing existing drugs as inhibitors of the main COVID-19 protease is a good approach.Among natural phenolic compounds found in plants, fruit, and vegetables; flavonoids are the most abundant. Flavonoids, especially in their glycosylated forms, display a number of physiological activities, which makes them interesting to investigate as antiviral molecules.The flavonoids chemical structures were downloaded from PubChem and protease structure 6lu7 was from the Protein Data Bank site. Molecular docking study was performed using AutoDock Vina. Among the tested molecules Quercetin-3-O-rhamnoside showed the highest binding affinity (-9,7 kcal/mol). Docking studies showed that glycosylated flavonoids are good inhibitors for the covid-19 protease and could be further investigated by in vitro and in vivo experiments for further validation.

scholarly journals Field-Template, QSAR, Ensemble Molecular Docking, and 3D-RISM Solvation Studies Expose Potential of FDA-Approved Marine Drugs as SARS-CoVID-2 Main Protease Inhibitors

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 936
Author(s):  
Poonam Kalhotra ◽  
Veera C. S. R. Chittepu ◽  
Guillermo Osorio-Revilla ◽  
Tzayhri Gallardo-Velazquez
Keyword(s):  
Molecular Docking ◽  
Protease Inhibitors ◽  
Active Site ◽  
World Health ◽  
Therapeutic Drug ◽  
Eribulin Mesylate ◽  
Infected People ◽  
Molecular Features ◽  
Main Protease

Currently, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has infected people among all countries and is a pandemic as declared by the World Health Organization (WHO). SARS-CoVID-2 main protease is one of the therapeutic drug targets that has been shown to reduce virus replication, and its high-resolution 3D structures in complex with inhibitors have been solved. Previously, we had demonstrated the potential of natural compounds such as serine protease inhibitors eventually leading us to hypothesize that FDA-approved marine drugs have the potential to inhibit the biological activity of SARS-CoV-2 main protease. Initially, field-template and structure–activity atlas models were constructed to understand and explain the molecular features responsible for SARS-CoVID-2 main protease inhibitors, which revealed that Eribulin Mesylate, Plitidepsin, and Trabectedin possess similar characteristics related to SARS-CoVID-2 main protease inhibitors. Later, protein–ligand interactions are studied using ensemble molecular-docking simulations that revealed that marine drugs bind at the active site of the main protease. The three-dimensional reference interaction site model (3D-RISM) studies show that marine drugs displace water molecules at the active site, and interactions observed are favorable. These computational studies eventually paved an interest in further in vitro studies. Finally, these findings are new and indeed provide insights into the role of FDA-approved marine drugs, which are already in clinical use for cancer treatment as a potential alternative to prevent and treat infected people with SARS-CoV-2.

scholarly journals COUMARIN ANALOGUES AS A POTENTIAL INHIBITOR OF LEISHMANIASIS: A MULTI-TARGETING PROTEIN INHIBITION APPROACH BY MOLECULAR DOCKING

2019 ◽  
Author(s):  
Kapish Kapoor
Keyword(s):  
Molecular Docking ◽  
Amino Acid ◽  
Active Compound ◽  
Active Site ◽  
Therapeutic Potential ◽  
Docking Study ◽  
Developed Countries ◽  
Molecular Docking Study

Leishmaniasis is one of the most dreadful diseases as a leading cause of death in most of the developed countries. In the given study molecular docking study was performed on the library of coumarin analogues as anti-leishmaniasis agents. Total 300 coumarins analogues were taken from Pubmed and were studied using a molecular docking study on trypanothione reductase from Leishmania infantum (PDB code: 2JK6 and 2P18) and Leishmania mexicana (PDB code: 3PP7). Molecular docking result revealed that most active compound COU-130 and COU-220 bind to the active site of the protein with amino acids present in the various proteins. In PDB 2JK6 the active compound binds to the amino acid thr-51 and ser-14 were binding to the active site, and in PDB 3PP7 the active compound binds amino acid thr-26 and in PDB 2P18 the active compound binds to the amino acid phe-219 and try-212. Further in vitro and in vivo study of selected coumarin analogues can be studied for their therapeutic potential in treating leishmaniasis.

Some FDA Approved drugs exhibit binding affinity as high as -16.0 kcal/mol against COVID-19 Main Protease (Mpro): A Molecular Docking Study

2020 ◽  
Author(s):  
Shanmuga Subramanian
Keyword(s):  
Clinical Trials ◽  
Molecular Docking ◽  
Antiviral Agent ◽  
Binding Energies ◽  
In Vitro Tests ◽  
Molecular Docking Study ◽  
Main Protease ◽  
Approved Drugs ◽  
Fda Approved Drugs

Currently the new Coronavirus "COVID-19", also known as SARS-CoV-2, has infected nearly 3 million patients and nearly 200,000+ people have lost their lives due to this pandemic. There is an urgent need to find an antiviral agent that may slow down the spread of the virus. The aim of this study is to assess and evaluate some FDA Approved drugs as potential inhibitors for COVID-19 Main Protease (Mpro) (PDB code: 6LU7). This will be done by blind molecular docking using PyRx and Auto Vina software. The compounds Hydroxychloroquine and Remdesivir were used for comparative study. The binding energies obtained from the docking of 6LU7 with Midostaurin, Zafirlukast, Eluxadoline, Naldemedine, Netupitant, Pancuronium, Letermovir, Baloxavir marboxil, Tazemetostat, Telotristat ethyl, Zeaxanthin, Lutein, Deserpidine, Cefotetan, Procaine benzylpenicillin were -16, 15.6, -15.3, -15.2, -15.1, -14.8, -14.6, -14.5, -13.8, -13.2, -13.2, -12.4, -12.4 and -11.2 kcal/mol respectively . Therefore some of the drugs can be used in Clinical trials as they are purified compounds of known composition and among all of them are approved drugs,some of them are investigative drugs except Pancuronium. All these drugs should be evaluated for further use by conducting in vitro tests and if they are successful they should evaluated for further use in clinical trials against COVID-19 as they are readily available in the market.

scholarly journals Ascertain of Antihypertensive Bioactive Compounds from Rosemary and Hawthorn; A Molecular Docking Study

2021 ◽  
pp. 42-59
Author(s):  
Mohamed Ismail Draou ◽  
Salim Bouchentouf ◽  
Nadia Kambouche ◽  
Salima Bellahouel
Keyword(s):  
Blood Pressure ◽  
Molecular Docking ◽  
Angiotensin Converting Enzyme ◽  
Arterial Hypertension ◽  
Premature Death ◽  
World Health ◽  
Converting Enzyme ◽  
Molecular Docking Study

Blood pressure disorder causes serious diseases in the cardiovascular system such as arterial hypertension. According to the World Health Organization, an estimated 1.13 billion people worldwide have hypertension, and most of them (two-thirds) live in low- and middle-income countries. It is poorly controlled and constitutes one of the leading causes of premature death. In Africa, nearly 40% of adults in many countries have high blood pressure, but most wouldn't even know it. In 2019, Algeria announced that 24% of the population suffers from the arterial hypertension and around 72% of those who were tested positive had not received treatment. Among the processes related to hypertension, the angiotensin converting enzyme I (ACE) plays an important role in the regulation of the blood pressure. The talk about the high potential of the hawthorn and rosemary plants to treat hypertension was so spread in the Algerian culture, which prompted to study the molecules of these plants and descript they behavior with the angiotensin-converting enzyme by calculating energy affinity. Using molecular docking approach, identification and evaluation of the inhibitory potential of ACE by selected herbs was attempted. In addition, and in order  to identify the most suitable molecules which can be developed to oral drugs considering their adsorption, distribution, metabolism, and excretion (ADME), Lipinski’s rules were applied using free  SwissADME tool. Our study provides clearer insight interaction properties of known putative inhibitors of ACE such as Caffeic acid, Quercetin, Luteolin, Eugenol, Rosmaquinone, and Rosmaquinone β, which may be developed into drugs after in-vitro and in-vivo tests and also encourage use of medicinal herbs for treatment of arterial hypertension. 

scholarly journals Identification of Potent Inhibitors of COVID-19 Main Protease Enzyme by Molecular Docking Study

2020 ◽  
Author(s):  
pooja singh ◽  
Angkita Sharma ◽  
Shoma Paul Nandi
Keyword(s):  
Molecular Docking ◽  
Antiviral Drug ◽  
Cyclopiazonic Acid ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Docking Score ◽  
Protease Enzyme ◽  
Main Protease

<p>Within the span of a few months, the severe acute respiratory syndrome coronavirus, COVID-19 (SARS-CoV-2), has proven to be a pandemic, affecting the world at an exponential rate. It is extremely pathogenic and causes communicable infection in humans. Viral infection causes difficulties in breathing, sore throat, cough, high fever, muscle pain, diarrhea, dyspnea, and may lead to death. Finding a proper drug and vaccines against this virus is the need of the hour. The RNA genome of COVID19 codes for the main protease M<sup>pro</sup>, which is required for viral multiplication. To identify possible antiviral drug(s), we performed molecular docking studies. Our screen identified ten biomolecules naturally present in <i>Aspergillus flavus</i> and <i>Aspergillus oryzae</i> fungi. These molecules include Aspirochlorine, Aflatoxin B1, Alpha-Cyclopiazonic acid, Sporogen, Asperfuran, Aspergillomarasmine A, Maltoryzine, Kojic acid, Aflatrem and Ethyl 3-nitropropionic acid, arranged in the descending order of their docking score. Aspirochlorine exhibited the docking score of – 7.18 Kcal/mole, higher than presently used drug Chloroquine (-6.2930522 Kcal/mol) and out of ten ligands studied four has docking score higher than chloroquine. These natural bioactive compounds could be tested for their ability to inhibit viral growth <i>in- vitro</i> and <i>in-vivo</i>.<b> </b></p>

Structure-Based Design, Synthesis, Biological Evaluation and Molecular Docking Study of 4-Hydroxy-N'-methylenebenzohydrazide Derivatives Acting as Tyrosinase Inhibitors with Potentiate Anti-Melanogenesis Activities

2020 ◽  
Vol 16 (7) ◽  
pp. 892-902 ◽  
Author(s):  
Aida Iraji ◽  
Mahsima Khoshneviszadeh ◽  
Pegah Bakhshizadeh ◽  
Najmeh Edraki ◽  
Mehdi Khoshneviszadeh
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Competitive Inhibition ◽  
Docking Study ◽  
Biological Evaluation ◽  
Primary Response ◽  
Ratio Method ◽  
Molecular Docking Study ◽  
Metal Chelating

Background: Melanogenesis is a process of melanin synthesis, which is a primary response for the pigmentation of human skin. Tyrosinase is a key enzyme, which catalyzes a ratelimiting step of the melanin formation. Natural products have shown potent inhibitors, but some of these possess toxicity. Numerous synthetic inhibitors have been developed in recent years may lead to the potent anti– tyrosinase agents. Objective: A number of 4-hydroxy-N'-methylenebenzohydrazide analogues with related structure to chalcone and tyrosine were constructed with various substituents at the benzyl ring of the molecule and evaluate as a tyrosinase inhibitor. In addition, computational analysis and metal chelating potential have been evaluated. Methods: Design and synthesized compounds were evaluated for activity against mushroom tyrosinase. The metal chelating capacity of the potent compound was examined using the mole ratio method. Molecular docking of the synthesized compounds was carried out into the tyrosine active site. Results: Novel 4-hydroxy-N'-methylenebenzohydrazide derivatives were synthesized. The two compounds 4c and 4g showed an IC50 near the positive control, led to a drastic inhibition of tyrosinase. Confirming in vitro results were performed via the molecular docking analysis demonstrating hydrogen bound interactions of potent compounds with histatidine-Cu+2 residues with in the active site. Kinetic study of compound 4g showed competitive inhibition towards tyrosinase. Metal chelating assay indicates the mole fraction of 1:2 stoichiometry of the 4g-Cu2+ complex. Conclusion: The findings in the present study demonstrate that 4-Hydroxy-N'- methylenebenzohydrazide scaffold could be regarded as a bioactive core inhibitor of tyrosinase and can be used as an inspiration for further studies in this area.

scholarly journals Therapeutic Effectiveness and Safety of Repurposing Drugs for the Treatment of COVID-19: Position Standing in 2021

2021 ◽  
Vol 12 ◽  
Author(s):  
Safaet Alam ◽  
Taslima Binte Kamal ◽  
Md. Moklesur Rahman Sarker ◽  
Jin-Rong Zhou ◽  
S. M. Abdur Rahman ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Case Series ◽  
Basic Knowledge ◽  
World Health ◽  
Current Status ◽  
Drug Candidates ◽  
Health Organization ◽  
Meta Analyses

COVID-19, transmitted by SARS-CoV-2, is one of the most serious pandemic situations in the history of mankind, and has already infected a huge population across the globe. This horrendously contagious viral outbreak was first identified in China and within a very short time it affected the world's health, transport, economic, and academic sectors. Despite the recent approval of a few anti-COVID-19 vaccines, their unavailability and insufficiency along with the lack of other potential therapeutic options are continuing to worsen the situation, with valuable lives continuing to be lost. In this situation, researchers across the globe are focusing on repurposing prospective drugs and prophylaxis such as favipiravir, remdesivir, chloroquine, hydroxychloroquine, ivermectin, lopinavir-ritonavir, azithromycin, doxycycline, ACEIs/ARBs, rivaroxaban, and protease inhibitors, which were preliminarily based on in vitro and in vivo pharmacological and toxicological study reports followed by clinical applications. Based on available preliminary data derived from limited clinical trials, the US National Institute of Health (NIH) and USFDA also recommended a few drugs to be repurposed i.e., hydroxychloroquine, remdesivir, and favipiravir. However, World Health Organization later recommended against the use of chloroquine, hydroxychloroquine, remdesivir, and lopinavir/ritonavir in the treatment of COVID-19 infections. Combining basic knowledge of viral pathogenesis and pharmacodynamics of drug molecules as well as in silico approaches, many drug candidates have been investigated in clinical trials, some of which have been proven to be partially effective against COVID-19, and many of the other drugs are currently under extensive screening. The repurposing of prospective drug candidates from different stages of evaluation can be a handy wellspring in COVID-19 management and treatment along with approved anti-COVID-19 vaccines. This review article combined the information from completed clinical trials, case series, cohort studies, meta-analyses, and retrospective studies to focus on the current status of repurposing drugs in 2021.

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