scholarly journals Investigation of Anti-Coronavirus, Anti-HCV, Nucleotide Inhibitors, and Bioactive Molecules efficacy Against RNA-directed RNA polymerase of Nipah Virus: Molecular Docking Study

2021 ◽  
Author(s):  
Peter T. Habib
Keyword(s):  
Molecular Docking ◽  
Rna Polymerase ◽  
Nipah Virus ◽  
Docking Study ◽  
The Philippines ◽  
Bioactive Molecules ◽  
World Health ◽  
Energy Estimates ◽  
Toxicity Tests ◽  
Molecular Docking Study

Abstract The infections with the Nipah virus (NiV) are highly infectious and may lead to severe febrile encephalitis. High rates of mortality in southeastern Asia including Bengal, Malaysia, Papua New Guinea, Vietnam, Cambodia, Indonesia, Madagascar, the Philippines, Thailand, and India have been reported in NiV outbreaks. Considering the high risk of an epidemic, NiV was declared a priority pathogen by the World Health Organization (WHO). However, for the treatment of this infection, there is no effective therapy or approved FDA medicines. RNA-dependent polymerase RNA (RdRp) plays an important role in viral replication among the nine well-known proteins of NiV. Therefore, fourteen antiviral molecules have been computerized for NiV RNA-dependent RNA polymerase and demonstrated a potential inhibition effect against coronavirus (NiV-RdRp). A multi-step molecular docking process, followed by extensive analyzes of molecular binding interactions, binding energy estimates, synthetic accessibility assessments, and toxicity tests. Analysis reveals that Uprifosbuvir is the most suitable inhibitor for RdRp of Nipah Virus regarding the binding affinity and binding in the target cavity. Although, such studies need clinical confirmation.

scholarly journals Investigation of Anti-Coronavirus, Anti-HCV, Nucleotide Inhibitors, and Bioactive Molecules efficacy Against RNA-directed RNA polymerase of Nipah Virus: Molecular Docking Study

2021 ◽  
Author(s):  
Peter T. Habib
Keyword(s):  
Molecular Docking ◽  
Rna Polymerase ◽  
Nipah Virus ◽  
Docking Study ◽  
The Philippines ◽  
Bioactive Molecules ◽  
World Health ◽  
Energy Estimates ◽  
Toxicity Tests ◽  
Molecular Docking Study

Abstract The infections with the Nipah virus (NiV) are highly infectious and may lead to severe febrile encephalitis. High rates of mortality in southeastern Asia including Bengal, Malaysia, Papua New Guinea, Vietnam, Cambodia, Indonesia, Madagascar, the Philippines, Thailand, and India have been reported in NiV outbreaks. Considering the high risk of an epidemic, NiV was declared a priority pathogen by the World Health Organization (WHO). However, for the treatment of this infection, there is no effective therapy or approved FDA medicines. RNA-dependent polymerase RNA (RdRp) plays an important role in viral replication among the nine well-known proteins of NiV. Therefore, fourteen antiviral molecules have been computerized for NiV RNA-dependent RNA polymerase and demonstrated a potential inhibition effect against coronavirus (NiV-RdRp). A multi-step molecular docking process, followed by extensive analyzes of molecular binding interactions, binding energy estimates, synthetic accessibility assessments, and toxicity tests. Analysis reveals that Uprifosbuvir is the most suitable inhibitor for RdRp of Nipah Virus regarding the binding affinity and binding in the target cavity. Although, such studies need clinical confirmation.

scholarly journals Investigation of Anti-Coronavirus, Anti-HCV, Nucleotide Inhibitors, and Bioactive Molecules efficacy Against RNA-directed RNA polymerase of Nipah Virus: Molecular Docking Study

2021 ◽  
Vol 10 (1) ◽  
pp. 78
Author(s):  
Peter T. Habib
Keyword(s):  
Molecular Docking ◽  
Rna Polymerase ◽  
Nipah Virus ◽  
Docking Study ◽  
The Philippines ◽  
Bioactive Molecules ◽  
World Health ◽  
Energy Estimates ◽  
Molecular Docking Study ◽  
Rna Dependent Rna Polymerase

Introduction: The infections with the Nipah virus (NiV) are highly infectious and may lead to severe febrile encephalitis. High mortality rates in southeastern Asia, including Bengal, Malaysia, Papua New Guinea, Vietnam, Cambodia, Indonesia, Madagascar, the Philippines, Thailand, and India, have been reported in NiV outbreaks. Considering the high risk of an epidemic, NiV was declared a priority pathogen by the World Health Organization. However, for the treatment of this infection, there is no effective therapy or approved FDA medicines. RNA-dependent polymerase RNA (RdRp) plays an important role in viral replication among the nine well-known proteins of NiV.Material and Methods: Fourteen antiviral molecules have been computerized for NiV RNA-dependent RNA polymerase and demonstrated a potential inhibition effect against coronavirus (NiV-RdRp). A multi-step molecular docking process, followed by extensive analyzes of molecular binding interactions, binding energy estimates, synthetic accessibility assessments, and toxicity tests.Results: Molecular docking analysis reveals that Uprifosbuvir is the most suitable inhibitor for RdRp of Nipah Virus regarding the binding affinity and binding in the target cavity. Although, such studies need clinical confirmation.Conclusion: The role of anti-viral molecules as a ligand against RNA-dependent RNA polymerase is critical important in the current era. Computational tools such as molecular docking has proven its power in the analysis of molecules interaction. Our analysis reveals the Uprifosbuvir might be a candidate RdRp inhibitor. This study should further investigate the properties of the already identified anti-viral molecules followed by a pharmacological investigation of these in-silico findings in suitable models.

scholarly journals Putative Molecular Mechanisms of Neuroprotective Cerebrosides and Their Docking Studies on Acetyl Cholinesterase Enzyme Inhibition for the Treatment of Alzheimer’s Disease

2021 ◽  
Author(s):  
SHAIK IBRAHIM KHALIVULLA ◽  
Kokkanti Mallikarjuna
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Enzyme Inhibition ◽  
Docking Study ◽  
Tau Proteins ◽  
World Health ◽  
Molecular Docking Study ◽  
Ache Inhibitors ◽  
Catalytic Active Site

Abstract The Dementia disease is characterised by neuropsychiatric disturbances due to lack of proper synaptic communication between neurons causing the cognitive behavioural problems. The Alzheimer’s disease (AD) in elderly population is one of the several forms of Dementia. Recent data by World Health Organisation indicates that nearly 10 million people are getting dementia every year, of which 60-70% accounts for AD. The etiology of AD involves the formation of amyloid-β plaques and neurofibrillary Tau tangles in the brain resulting in the death of neural cells. There is no permanent solution for AD treatment, except the FDA approved drugs like galantamine, donepezil, rivastigmine and memantine that are normally associated with side effects. At this juncture, cerebrosides, the natural secondary metabolites identified from different taxa with potential neuroprotective effects offer a promising scope for the treatment of AD. In this paper, cerebrosides reported from all taxa are pooled up along with their functions and listed. The review of literature revealed that Cerebrosides can increase the cognitive functions by regulating or interacting with the N-methyl-d-aspartate (NMDA) calcium ion (Ca2+) channels at post-synaptic receptor; nitric oxide (NO); Bcl2, Bax, amyloid precursor (APP) and Tau proteins; brain-derived neurotrophic factor (BDNF) and cAMP- response element-binding proteins (CREB).This indicates that the Cerebrosides could be potential therapeutic agents for the protection of neurons involved in neurodegenerative disease like Alzheimer’s disease. The current neuroprotective drugs are AChE inhibitors; hence, in the present investigation, in silico molecular docking study on cerebrosides for the inhibition of AChE was assessed to find out their capacity to interact with an active catalytic site of AChE. The results of present investigation revealed that all 22 cerebrosides selected for this work interacted with catalytic active site of AChE measured in terms of Gibbs free binding energy. Of all the cerebrosides assessed, compound 6 exhibited strong interaction, followed by 15. This is the first report of molecular docking study on cerebrosides for AChE enzyme inhibition for treatment of Alzheimer’s disease. Nevertheless, detailed in vitro and in vivo, biochemical and molecular investigations are needed to bring them to useful form.

Novel 3-Substituted-2, 3-Dihydro-2-Thioxoquinazolin-4-(1H)-one derivative as Anticonvulsants: Synthesis, Molecular Docking and Pharmacological Screening

2020 ◽  
Vol 17 (6) ◽  
pp. 757-771 ◽  
Author(s):  
Nimisha jain ◽  
Pradeep Kumar Singour
Keyword(s):  
Molecular Docking ◽  
Anticonvulsant Activity ◽  
Type A ◽  
Docking Study ◽  
Aminobutyric Acid ◽  
World Health ◽  
Maximal Electroshock ◽  
Gamma Aminobutyric Acid ◽  
Molecular Docking Study ◽  
Acid Type

Background: According to the World Health Organization, 50 million people worldwide are suffering from epilepsy, making it one of the most common neurological diseases globally. 2,3 disubstituted quinazolinone-4-one derivatives endowed with various pharmacological activity, particularly having anticonvulsant action. Objectives: The aim of this study was to synthesize 3-Substituted-2,3-Dihydro-2-thioxoquinazolin- 4-(1H)-one derivative and evaluate for anticonvulsant activity and neurotoxicity in order to find an efficient, compound with lesser side effects. Methods: A novel series of 3-[4-(2-amino-5, 6-dihydro-4(substituted phenyl)-4H-1, 3-oxazin /thiazin-6yl) phenyl]-2, 3-dihyro-2-thioxoquinazolin-4(1H)-one derivatives (4a-4p) were synthesized. The structures of the synthesized compounds were assigned on the basis of spectral data (UV, IR, 1HNMR, 13CNMR and MS) and performed anticonvulsant activity against maximal electroshock test and Subcutaneous Pentylenetetrazole model. Neurotoxicity was assessed using a rotarod apparatus test. The molecular docking study was performed to assess their binding affinities towards Gamma-Aminobutyric Acid type A receptor. A quantitative estimate of drug-likeness was also performed, which calculates the molecular properties and screen the molecules based on drug-likeness rules. Results: Compounds 4b, 4e, 4j and 4m have shown the highest anticonvulsant activity against tonic seizure with decreased mean duration of tonic hind leg extension of 8.31, 7.35, 8.61 and 8.99 s, respectively in maximal electroshock model and increased onset time clonic convulsion duration of 94.45, 96.65, 93.51 and 91.86 s in Subcutaneous Pentylenetetrazole model. Molecular docking study revealed a better binding affinity with Gamma-Aminobutyric Acid type A receptor. Conclusion: The compound 4b and 4e emerged out as the pilot molecule with a better anticonvulsant activity without any neurotoxicity. The obtained results showed that compounds 4b and 4e could be useful as a template for future design, optimization, and investigation to produce more active analogs.

scholarly journals Naturally Occurring Anthraquinones as Potential Inhibitors of SARS-CoV-2 Main Protease: A Molecular Docking Study

2020 ◽  
Author(s):  
Sourav Das ◽  
Atanu Singha Roy
Keyword(s):  
Molecular Docking ◽  
Drug Targets ◽  
Docking Study ◽  
Docking Studies ◽  
World Health ◽  
Molecular Docking Study ◽  
Inhibitory Potential ◽  
Novel Coronavirus ◽  
Health Organization ◽  
Potential Inhibitors

<i>Background:</i> The novel coronavirus (COVID-19) has quickly spread throughout the globe, affecting millions of people. The World Health Organization (WHO) has recently declared this infectious disease as a pandemic. At present, several clinical trials are going on to identify possible drugs for treating this infection. SARS-CoV-2 M<sup>pro</sup> is one of the most critical drug targets for the blockage of viral replication. <i>Method:</i> The blind molecular docking analyses of natural anthraquinones with SARS-CoV-2 M<sup>pro</sup> were carried out in an online server, SWISSDOCK, which is based on EADock DSS docking software. <i>Results: </i>Blind molecular docking studies indicated that several<i> </i>natural antiviral anthraquinones could prove to be effective inhibitors for SARS-CoV-2 M<sup>pro</sup> of COVID-19 as they bind near the active site having the catalytic dyad, HIS41 and CYS145 through non-covalent forces. The anthraquinones showed less inhibitory potential as compared to the FDA approved drug, remdesivir.<i></i> <p><b><i>Conclusion:</i></b><i> </i>Among the natural anthraquinones<i>, </i>alterporriol Q could be the most potential inhibitor of SARS-CoV-2 M<sup>pro</sup> among the natural anthraquinones studied here, as its ∆<i>G</i> value differed from that of remdesivir only by 0.51 kcal/ mol. The uses of these alternate compounds might be favorable for the treatment of the COVID-19.</p>

scholarly journals Potential Phytochemical Inhibitors of the Coronavirus RNA Dependent RNA Polymerase: A Molecular Docking Study

2020 ◽  
Author(s):  
Ardra. P ◽  
Prachi Singh ◽  
Hariprasad VR ◽  
Babu UV ◽  
Mohamed Rafiq ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Rna Polymerase ◽  
Metal Ion ◽  
Docking Study ◽  
Nucleoside Triphosphate ◽  
Root Extract ◽  
Amino Acid Residues ◽  
Molecular Docking Study ◽  
Rna Dependent Rna Polymerase ◽  
Phytochemical Compounds

Abstract The COVID-19 disease that originated in China by the end of 2019 has now become a pandemic and has affected 216 countries as on 08 June 2020. RNA dependent RNA polymerase (RdRp), the core enzyme in the multiprotein replicase-transcriptase complex of coronaviruses, serves as a classical target for inhibiting the coronavirus infectivity. In this study we performed molecular docking of sixty-nine different phytochemical compounds from various herbs with RdRp of both SARS-CoV-2 and its predecessor SARS-CoV. Our results show that various phytochemical constituents from Withania somnifera root extract, Hyssopus officinalis and Camellia sinensis leaf extract have high binding affinity towards RdRps and are comparable to the small molecule drug remdesivir. Their binding interactions reveal that they bind to the amino acid residues involved in nucleoside triphosphate (NTP) entry and recognition site and metal ion cofactor chelating site of both SARS-CoV-2 and SARS-CoV. Hence they are different from the classical nucleotide analog inhibitors of RdRp. This study paves a quick platform for development of targeted therapy using phytochemicals for COVID-19 and other potential SARS coronavirus related outbreaks in future.

Petra/Osiris/Molinspiration and Molecular Docking Analyses of 3-Hydroxy-Indolin-2-one Derivatives as Potential Antiviral Agents

2019 ◽  
Vol 16 ◽  
Author(s):  
Taibi Ben Hadda ◽  
Vesna Rastija ◽  
Faisal AlMalki ◽  
Abderrahim Titi ◽  
Rachid Touzani ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Structural Parameters ◽  
Antiviral Agents ◽  
Chemical Properties ◽  
Docking Study ◽  
Bioactive Molecules ◽  
Geometrical Parameters ◽  
Molecular Docking Study ◽  
Catalytic Core ◽  
Hiv 1

Background: Studies on the interaction between bioactive molecules and HIV-1 virus has been the focus of recent research in the scope of medicinal chemistry and pharmacology. Objective: Investigating the structural parameters and physic-chemical properties of elucidating and identifying of the antiviral pharmacophore sites. Method: A mixed computational Petra/Osiris/Molinspiration/DFT (POM/DFT) based model has been developed for the identification of physico-chemical parameters governing the bioactivity of 22 3-hydroxy-indolin-2-one derivatives of diacetyl-L-tartaric acid and aromatic amines containing combined antiviral/antitumor/antibacterial pharmacophore sites. Molecular docking study was carried out with HIV-1 integrase (pdb ID: 5KGX) in order to provide information about interactions in the binding site of enzyme. Results: The POM analyses of physic-chemical properties and geometrical parameters of compounds 3a-5j, show that they are bearing a two combined (O,O)-pockets leading to a special platform which able to coordinate two transition metals. The increased activity of series 3a-5j, as compared to standard drugs, contains an (Osp2,O sp3,O sp2)-pharmacophore site. The increase of bioactivity from 4b (R1, R2 = H, H) to 3d (R1, R2 = 4-Br, 2-OCH3) could be attributed to the existence of pi-charge transfer from para-bromo-phenyl to its amid group (COδ---NHδ+). Similar to the indole-based reference ligand (pdb: 7SK), compound 3d forms hydrogen bonding interactions between the residues Glu170, Thr174 and His171 of HIV-1 integrase in catalytic core domain of enzyme. Conclusion: Study confirmed the importance of oxygen atoms, especially from the methoxy group of the phenyl ring, and electrophilic amide nitrogen atom for formation of interactions.

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