Molecular Docking suggests repurposing of Brincidofovir as a potential drug targeting SARS-CoV-2 "COVID-19" ACE2 receptor and main protease

2020 ◽  
Author(s):  
Mostafa A. Hussien ◽  
Ahmed E.M. Abdelaziz
Keyword(s):  
Clinical Trials ◽  
Molecular Docking ◽  
Ether Lipid ◽  
Respiratory Disorder ◽  
Main Protease ◽  
Life Threatening ◽  
Current Outbreak ◽  
Lipid Ester ◽  
Approved Drugs ◽  
Fda Approved Drugs

Abstract The current outbreak of the highly transmittable and life-threatening treme intense respiratory disorder coronavirus 2 (SARS-CoV-2) has advanced rapidly and posed a global health emergency. Many clinical trials are now being conducted to test possible therapies. To assist, the molecular docking was applied on some selected FDA-approved drugs, previously used in epidemics, and the top ten compounds were selected. These ten well-characterized drugs, previously used to treat Malaria and Ebola infections, were screened based on their interactions with the SARS-CoV-2 ACE2 Receptor and 3C-like Protease. Compared to the other nine medicines, Brincidofovir, an ether lipid ester analog of cidofovir with potent antiviral activity, showed the highest docking scores and binding interactions. Therefore, Brincidofovir worth further investigations and clinical trials as a possible therapeutic agent for the COVID-19 disease .

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 Repurposing FDA-Approved Drugs for COVID-19 Using a Data-Driven Approach

2020 ◽  
Author(s):  
Rodrigo R. R. Duarte ◽  
Dennis C. Copertino Jr. ◽  
Luis P. Iñiguez ◽  
Jez L. Marston ◽  
Douglas F. Nixon ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Drug Repositioning ◽  
Data Driven ◽  
Transcriptional Signature ◽  
Lung Carcinoma Cells ◽  
Main Protease ◽  
Data Driven Approach ◽  
Approved Drugs ◽  
Fda Approved Drugs

<p>There have been more than 116,000 recorded deaths worldwide to-date caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the etiological agent of the Coronavirus Disease 2019 (COVID-19), and over 1.8 million individuals are currently infected. Although there are now hundreds of clinical trials for COVID-19, there are currently no effective licensed treatments, while the numbers of infected individuals continue to rise at an exponential rate in many parts of the world. Here, we used a data-driven approach utilizing connectivity mapping and the transcriptional signature of lung carcinoma cells infected with SARS-CoV-2, to search for drugs across the spectrum of medicine that have repurposing potential for treating COVID-19. We also performed chemoinformatic analyses to test whether the identified compounds were predicted to physically interact with the SARS-CoV-2 RNA-dependent RNA polymerase or main protease enzymes. Our study identified commonly prescribed FDA-approved molecules as important candidates for drug repositioning against COVID-19, including flupentixol, reserpine, fluoxetine, trifluoperazine, sunitinib, atorvastatin, raloxifene, butoconazole, and metformin. These drugs should not be taken for treating or preventing COVID-19 without a doctor’s advice, as further research and clinical trials are now needed to elucidate their efficacy for this purpose.</p>

scholarly journals Potential Inhibitors of SARS-CoV-2 Main Protease (Mpro) Identified from the Library of FDA Approved Drugs Using Molecular Docking Studies

2020 ◽  
Author(s):  
Dipesh Verma ◽  
Srajan Kapoor ◽  
Satyajeet Das ◽  
Krishan Thakur
Keyword(s):  
Molecular Docking ◽  
Therapeutic Potential ◽  
Docking Studies ◽  
Antiviral Compound ◽  
Molecular Docking Studies ◽  
Main Protease ◽  
Approved Drugs ◽  
Fda Approved Drugs

Corona Virus Infectious Disease-2019 (COVID-19) outbreak originated recently at Wuhan, China in December 2019. It has already spread rapidly to more than 200 countries and has been declared a pandemic by WHO. It is caused by a beta-coronavirus named as SARS-CoV-2. There is no definitive cure, either drug or vaccine, to treat or prevent this viral disease. Recently, the crystal structure of the main protease Mpro has been determined. Mpro is responsible for the proteolytic maturation of the polyprotein essential for the viral replication and transcription, which makes it an important drug target. The discovery of new drug molecules may take years before getting to the clinics. So, considering urgency we performed molecular docking studies using FDA approved drugs to identify molecules that could potentially bind to the substrate-binding site and inhibit SARS-CoV-2 main protease (Mpro). We used the Glide module in Schrodinger software suite to perform molecular docking studies followed by MM-GBSA based energy calculations to score the hit molecules. Molecular docking and manual analysis suggest that several drugs may bind and potentially inhibit Mpro. We also performed molecular simulations studies for selected compounds to evaluate protein-drug interactions. Interestingly, we observed only one antiviral compound, Adefovir, in the top50 list of compounds. Considering bioavailability, lesser toxicity, route of administration some of the top-ranked drugs including lumefantrine (antimalarial), dipyridamole (coronary vasodilator), dihydroergotamine (used for treating migraine), hexoprenaline (anti- asthmatic), riboflavin (vitamin B2) and pantethine (vitamin B5) may be taken forward for further in vitro and in vivo experiments to investigate their therapeutic potential.

scholarly journals Repurposing FDA-Approved Drugs for COVID-19 Using a Data-Driven Approach

2020 ◽  
Author(s):  
Rodrigo R. R. Duarte ◽  
Dennis C. Copertino Jr. ◽  
Luis P. Iñiguez ◽  
Jez L. Marston ◽  
Douglas F. Nixon ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Drug Repositioning ◽  
Data Driven ◽  
Transcriptional Signature ◽  
Lung Carcinoma Cells ◽  
Main Protease ◽  
Data Driven Approach ◽  
Approved Drugs ◽  
Fda Approved Drugs

<p>There have been more than 116,000 recorded deaths worldwide to-date caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the etiological agent of the Coronavirus Disease 2019 (COVID-19), and over 1.8 million individuals are currently infected. Although there are now hundreds of clinical trials for COVID-19, there are currently no effective licensed treatments, while the numbers of infected individuals continue to rise at an exponential rate in many parts of the world. Here, we used a data-driven approach utilizing connectivity mapping and the transcriptional signature of lung carcinoma cells infected with SARS-CoV-2, to search for drugs across the spectrum of medicine that have repurposing potential for treating COVID-19. We also performed chemoinformatic analyses to test whether the identified compounds were predicted to physically interact with the SARS-CoV-2 RNA-dependent RNA polymerase or main protease enzymes. Our study identified commonly prescribed FDA-approved molecules as important candidates for drug repositioning against COVID-19, including flupentixol, reserpine, fluoxetine, trifluoperazine, sunitinib, atorvastatin, raloxifene, butoconazole, and metformin. These drugs should not be taken for treating or preventing COVID-19 without a doctor’s advice, as further research and clinical trials are now needed to elucidate their efficacy for this purpose.</p>

scholarly journals Molecular Docking and Virtual Screening based prediction of drugs for COVID-19

2020 ◽  
Vol 23 ◽  
Author(s):  
Sekhar Talluri
Keyword(s):  
Clinical Trials ◽  
Molecular Docking ◽  
Virtual Screening ◽  
Genomic Sequence ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
X Ray Diffraction ◽  
Main Protease ◽  
Docking Calculations ◽  
Approved Drugs

Aims: To predict potential drugs for COVID-19 by using molecular docking for virtual screening of drugs approved for other clinical applications. <p> Background: SARS-CoV-2 is the betacoronavirus responsible for the COVID-19 pandemic. It was listed as a potential global health threat by WHO due to high mortality, high basic reproduction number and lack of clinically approved drugs and vaccines for COVID-19. The genomic sequence of the virus responsible for COVID-19, as well as the experimentally determined three dimensional structure of the Main protease are available. <p> </p> Objective: To identify potential drugs that can be repurposed for treatment of COVID-19 by using molecular docking based virtual screening of all approved drugs. <p> </p> Methods: List of drugs approved for clinical use was obtained from SuperDRUG2 database. The structure of the target in the apo form, as well as structures of several target-ligand complexes, were obtained from RCSB PDB. The structure of SARS-CoV-2 Mpro determined from X-ray diffraction data was used as the target. Data regarding drugs in clinical trials for COVID-19 was obtained from clinicaltrials.org. Input for molecular docking based virtual screening was prepared by using Obabel and customized python, bash and awk scripts. Molecular docking calculations were carried out with Vina and SMINA, and the docked conformations were analyzed and visualized with PLIP, Pymol and Rasmol. <p> </p> Results: Among the drugs that are being tested in clinical trials for COVID-19, Danoprevir and Darunavir have the highest binding affinity for the target main protease of SARS-CoV-2. Saquinavir and Beclabuvir were identified as the best novel candidates for COVID-19 therapy by using Virtual Screening of drugs approved for other clinical indications. <p> </p> Conclusion: Protease inhibitors approved for treatment of other viral diseases have the potential to be repurposed for treatment of COVID-19. </p>

scholarly journals In Silico Molecular Docking and Ab initio DFT Studies as a Tool for a Quick Screening on Drug Inhibitors for SARS-Cov-2 RNA-Dependent Polymerase

2020 ◽  
Author(s):  
Manos C. Vlasiou ◽  
Kyriakos I. Ioannou ◽  
Kyriaki S. Pafiti
Keyword(s):  
Clinical Trials ◽  
Molecular Docking ◽  
Side Effects ◽  
In Silico ◽  
Binding Affinities ◽  
Dft Studies ◽  
Approved Drugs ◽  
In Silico Molecular Docking ◽  
Fda Approved Drugs ◽  
Ab Initio Dft

Abstract In silico molecular docking took place in order to evaluate already FDA approved drugs for several diseases, as inhibitors for SARSCov-2 RNA- dependent polymerase. The best candidates with the highest binding affinities, evaluated for their energy determined by their electron density. Remdesivir and Saquinavir seemed to be good candidates for clinical trials but their predicted toxicity based on their calculated structures revealed that these two substances should evaluated more for their side effects

scholarly journals Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Vicky Mody ◽  
Joanna Ho ◽  
Savannah Wills ◽  
Ahmed Mawri ◽  
Latasha Lawson ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Dynamics Simulation ◽  
Simulation Studies ◽  
Inhibitory Effects ◽  
Major Threat ◽  
Main Protease ◽  
Approved Drugs ◽  
Fda Approved Drugs ◽  
Computational Molecular Modeling

AbstractEmerging outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a major threat to public health. The morbidity is increasing due to lack of SARS-CoV-2 specific drugs. Herein, we have identified potential drugs that target the 3-chymotrypsin like protease (3CLpro), the main protease that is pivotal for the replication of SARS-CoV-2. Computational molecular modeling was used to screen 3987 FDA approved drugs, and 47 drugs were selected to study their inhibitory effects on SARS-CoV-2 specific 3CLpro enzyme in vitro. Our results indicate that boceprevir, ombitasvir, paritaprevir, tipranavir, ivermectin, and micafungin exhibited inhibitory effect towards 3CLpro enzymatic activity. The 100 ns molecular dynamics simulation studies showed that ivermectin may require homodimeric form of 3CLpro enzyme for its inhibitory activity. In summary, these molecules could be useful to develop highly specific therapeutically viable drugs to inhibit the SARS-CoV-2 replication either alone or in combination with drugs specific for other SARS-CoV-2 viral targets.

scholarly journals Screening of FDA Approved Drugs Against COVID-19 Main Protease: Coronavirus Disease

2020 ◽  
Author(s):  
Vijayakumar Balakrishnan ◽  
Karthik Lakshminarayanan
Keyword(s):  
Vaccine Development ◽  
New Drugs ◽  
World Health ◽  
Wuhan City ◽  
Drug Candidates ◽  
Human Contact ◽  
Main Protease ◽  
Potent Drug ◽  
Approved Drugs ◽  
Fda Approved Drugs

In the end of December 2019, a new strain of coronavirus was identified in the Wuhan city of Hubei province in China. Within a shorter period of time, an unprecedented outbreak of this strain was witnessed over the entire Wuhan city. This novel coronavirus strain was later officially renamed as COVID-19 (Coronavirus disease 2019) by the World Health Organization. The mode of transmission had been found to be human-to-human contact and hence resulted in a rapid surge across the globe where more than 1,100,000 people have been infected with COVID-19. In the current scenario, finding potent drug candidates for the treatment of COVID-19 has emerged as the most challenging task for clinicians and researchers worldwide. Identification of new drugs and vaccine development may take from a few months to years based on the clinical trial processes. To overcome the several limitations involved in identifying and bringing out potent drug candidates for treating COVID-19, in the present study attempts were made to screen the FDA approved drugs using High Throughput Virtual Screening (HTVS). The COVID-19 main protease (COVID-19 Mpro) was chosen as the drug target for which the FDA approved drugs were initially screened with HTVS. The drug candidates that exhibited favorable docking score, energy and emodel calculations were further taken for performing Induced Fit Docking (IFD) using Schrodinger&rsquo;s GLIDE. From the flexible docking results, the following four FDA approved drugs Sincalide, Pentagastrin, Ritonavir and Phytonadione were identified. In particular, Sincalide and Pentagastrin can be considered potential key players for the treatment of COVID-19 disease.

scholarly journals Mulberrofuran G, a Potent Inhibitor of SPIKE Protein of SARS Corona Virus 2

2021 ◽  
Author(s):  
Fatemeh Sadat Hosseini ◽  
Mohammad Reza Motamedi
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Active Site ◽  
Potential Role ◽  
Potent Inhibitor ◽  
Screening Method ◽  
Spike Protein ◽  
Treatment Agent ◽  
Approved Drugs ◽  
Fda Approved Drugs

Background: At the onset of the 2020 year, Coronavirus disease (COVID-19) has become a pandemic and infected many people worldwide. Despite all efforts, no cure was found for this infection. Bioinformatics and medicinal chemistry have a potential role in the primary consideration of drugs to treat this infection. With virtual screening and molecular docking, some potent compounds and medications can be found and modified and then applied to treat disease in the next steps. Methods: By virtual screening method and PRYX software, some Food and Drug Administration (FDA) approved drugs and natural compounds have been docked with the SPIKE protein of SARS-CoV-2. Some more potent agents have been selected, and then new structures are designed with better affinity than them. After that, we searched for the molecules with a similar structure to designed compounds to find the most potent compound to our target. Results: Because of the study of structures and affinities, mulberrofuran G was the most potent compound in this study. The compound has interacted strongly with residues in the probably active site of SPIKE. Conclusion: Mulberrofuran G can be a treatment agent candidate for COVID-19 because of its good affinity to SPIKE of the virus and inhibition of virus-cell adhesion and entrance.

Sign in / Sign up

Export Citation Format

Share Document