scholarly journals Computational Screening of FDA Approved Drugs from ZINC Database for Potential Inhibitors of Zika Virus NS2B/NS3 Protease: A Molecular Docking and Dynamics Simulation Study

2021 ◽  
pp. 308-319
Author(s):  
Hasanain Abdulhameed Odhar ◽  
Salam Waheed Ahjel ◽  
Zanan Abdulhameed Odhar
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Zika Virus ◽  
Computational Study ◽  
Dynamics Simulation ◽  
Computational Screening ◽  
Approved Drugs ◽  
Ns3 Protease ◽  
Fda Approved Drugs ◽  
Molecular Docking And Dynamics

Zika virus is a mosquito borne pathogen with a single strand RNA genome. Human infection with this virus is usually asymptomatic, however outbreaks reported in both Pacific region and Latin America have been associated with increase in frequency of microcephaly in newborns and fetuses of infected mothers. Also, the incidence of Guillain-Barré syndrome had also increased among adults with Zika virus infection. Currently, neither vaccine nor antiviral drug has been developed against Zika virus. Structure based virtual screening can be employed, through drug repurposing strategy, to accelerate the identification of potential anti-Zika virus candidates. As such, virtual screening of approved drugs against Zika virus NS2B/NS3 protease can help to recognize new hits capable of hindering viral ability to replicate and evade immune system of the host. In this computational study, we have screened 1615 FDA approved drugs against NS2B/NS3 protease enzyme of Zika virus by using both molecular docking and dynamics simulation. Our virtual screening results indicate that the anti-muscarinic agent Darifenacin and the anti-diarrheal agent Loperamide may have a promising capacity to inhibit Zika virus NS2B/NS3 protease. According to molecular docking and dynamics simulation, these two approved drugs have good binding capacity to NS2B/NS3 as reported by docking energy of binding and MM-PBSA binding energy. In addition, both Darifenacin and Loperamide were able to maintain close proximity to protease crystal throughout simulation period. However, invitro evaluation of these two drugs against Zika virus NS2B/NS3 protease is required to confirm these computational results.

scholarly journals Virtual Screening of FDA Approved Drugs Library to Identify a Potential Inhibitor against NS2B-NS3 Protease of Yellow Fever Virus

2021 ◽  
pp. 177-186
Author(s):  
Hasanain Abdulhameed Odhar ◽  
Salam Waheed Ahjel ◽  
Ali A. Mohammed Ali Albeer ◽  
Ahmed Fadhil Hashim ◽  
Suhad Sami Humadi
Keyword(s):  
Virtual Screening ◽  
Yellow Fever ◽  
Active Site ◽  
Yellow Fever Virus ◽  
Fever Virus ◽  
Dynamics Simulation ◽  
Hemorrhagic Disease ◽  
Approved Drugs ◽  
Ns3 Protease ◽  
Fda Approved Drugs

Yellow fever is a neglected hemorrhagic disease with a high case fatality rate ranging between 25% and 50% for the hospitalized patients. Yellow fever disease is caused by a zoonotic pathogen known as yellow fever virus. This RNA virus is usually transmitted by mosquitos and it is considered endemic in the tropical regions of South America and Africa. Although an effective vaccine is available for yellow fever virus, no antiviral drug is yet licensed against the disease. Thus, yellow fever virus is still representing a re-emerging threat among unvaccinated individuals in endemic regions. The NS2B-NS3 protease seems to play an important role in yellow fever virus replication cycle. As such, the NS2B-NS3 protease may represent a potential target for structure-based drug design and discovery. In this direction, computational approaches like virtual screening can be utilized to hasten the design of novel antivirals and/ or repurposing an already FDA approved drugs. In this in silico study, an FDA approved drugs library was screened against NS2B-NS3 protease crystal of yellow fever virus. Then the best hits with least energy of binding and ability of hydrogen bonding with key residues of protease active site were then selected and submitted to molecular dynamics simulation. And throughout simulation interval, only Olsalazine was able to stay in close proximity to the active site of protease crystal with least average MM-PBSA binding energy as compared to Dantrolene, Belinostat and Linezolid. This indicates that Olsalazine may have the best capacity to bind to NS2B-NS3 protease and interfere with its activity.

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.

scholarly journals Reappraisal of trifluperidol against Nsp3 as a potential therapeutic for novel COVID-19: a molecular docking and dynamics study

2021 ◽  
Author(s):  
Ajita Pandey ◽  
Mohit Sharma
Keyword(s):  
Infectious Disease ◽  
Molecular Dynamics ◽  
Antiviral Agents ◽  
Dynamics Simulation ◽  
Regression Methods ◽  
Fast Spreading ◽  
Approved Drugs ◽  
Fda Approved Drugs ◽  
Spreading Disease ◽  
Molecular Docking And Dynamics

Novel COVID-19 is a highly infectious disease that is caused by the recently discovered SARS-CoV-2. It is a fast-spreading disease that urgently requires therapeutics. The current study employed computational regression methods to target the ADP-ribose phosphatase (ADRP) domain of Nsp3 using FDA-approved drugs. Identified leads were further investigated using molecular dynamics simulation (MDS). The screening and MDS results suggest that trifluperidol could be a novel inhibitor of the ADRP domain of Nsp3. Trifluperidol could, therefore, be used to help control the spread of COVID-19, either alone or in combination with antiviral agents.

scholarly journals Computational Study of Novel Natural Inhibitors Targeting 3-Phosphoinositi-Dependent Protein Kinase 1(PDK1)

2021 ◽  
Author(s):  
Sheng Zhong ◽  
Zhen Guo ◽  
Gaojing Dou ◽  
Xiaye Lv ◽  
Xinhui Wang ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Protein Kinase ◽  
Virtual Screening ◽  
Binding Affinity ◽  
Natural Environment ◽  
Computational Study ◽  
Dynamics Simulation ◽  
Dependent Protein Kinase ◽  
Lead Compounds ◽  
Dependent Protein

Abstract Objective To screen ideal lead compounds with potential inhibition of 3-phosphoinositi-dependent protein kinase 1 (PDK1) from ZINC15 database, which is beneficial to drug design and improvement.Methods The Discovery Studio 4.5 computer-aided virtual screening technique was used to screen potential inhibitors of PDK1. Libdock was used for virtual screening and scoring of candidate compounds, ADME module was used for physical and chemical properties and toxicity analysis, and CDOCKER module was used for molecular docking analysis. The binding affinity of ligand-PDK1 was studied through molecular docking, and the stability of ligand-PDK1 in the natural environment was analyzed through molecular dynamics simulation.Results Two natural compounds ZINC00000157721 and ZINC000034189841 were screened from ZINC15 database. These two compounds have no CYP2D6 inhibition, easy to pass the blood-brain barrier, no hepatotoxicity, high binding affinity with PDK1, higher stability in the natural environment than positive drug BX-795, and stable existence.Conclusions The results show that ZINC00000157721 and ZINC000034189841 are ideal and safe lead compounds and have a potential inhibitory effect on PDK1. These compounds are safe candidates and may provide the basis and premise for the design and optimization of specific PDK1 inhibitors.

scholarly journals Simeprevir and Eltrombopag as Potential Inhibitors of SARS-CoV2 Proteases: A Molecular Docking and Virtual Screening Approach to Combat COVID-19

2020 ◽  
Author(s):  
Ananta Swargiary ◽  
AKALESH Verma ◽  
Manita Daimari ◽  
Mritunjoy Kumar Roy
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Binding Affinities ◽  
Screening Approach ◽  
Approved Drugs ◽  
Potential Inhibitors ◽  
Fda Approved Drugs ◽  
Virtual Screening Approach

The present study investigates the binding affinities of 61 FDA approved drugs against two key proteases of SARS-COV2, 3-chymotrypsin-like protease and papain-like protease. We also investigates the ADMET properties of the top 10 besting binding drugs to understand the drug likeness property.

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