scholarly journals Modification of Remdesivir as a Better Inhibitor of COVID-19: A Computational Docking Study

2020 ◽  
Author(s):  
Mita Shikder ◽  
Kazi Ahsan Ahmed ◽  
Tasnin Al Hasib ◽  
Md. Lutful Kabir
Keyword(s):  
Rna Polymerase ◽  
Antiviral Drug ◽  
Antiviral Agent ◽  
Respiratory Illness ◽  
Docking Study ◽  
New Drugs ◽  
Computational Docking ◽  
Recent Success ◽  
Trial Basis ◽  
Docking Calculations

<div>Coronavirus (COVID-19) mediated infection is a highly contagious respiratory illness that was initially found in Wuhan city of Hubei Province in China. The ongoing pandemic of the novel SARS-CoV-2 virus is affecting global health. Despite the recent success in vaccination on a trial basis, there is no treatment of the infection. Thus, establishing an effective therapeutic measure is of apex priority among biologists and healthcare professionals. Re-purposing Remdesivir, a broad-spectrum antiviral agent that inhibits viral RNA polymerase, has been found effective for the treatment of COVID-19. In this study, modification of the existing drug Remdesivir was done. In logical drug designing and development, molecular recognition plays a central role in this sphere. The anti viral function of Remdesivir is achieved by binding to RNA polymerase enzyme. The protein 7BTF is an RNA-dependent RNA polymerase that plays a crucial role in coronavirus replication and transcription machinery and it appears to be the primary target of the antiviral drug Remdesivir. The study intend to design derivative compounds form Remdesivir to screen out the a better drug against the SARS-CoV-2 virus by inhibiting the targeted protein. The efficacy of these new drugs was also tested by molecular docking calculations. The drug derivatives were docked for binding affinity and non-bond interactions. Pharmacokinetic activities of the designed drugs are also predicted. All the drugs are non-carcinogenic and chemically reactive. In our study, modified compound D-I has exhibited the best performance among Remdesivir and it’s derivatives. This study might provide an insight into the potential of a Remdesivir derivative in treating SARS-CoV-2 infection<br></div>

scholarly journals Modification of Remdesivir as a Better Inhibitor of COVID-19: A Computational Docking Study

2020 ◽  
Author(s):  
Mita Shikder ◽  
Kazi Ahsan Ahmed ◽  
Tasnin Al Hasib ◽  
Md. Lutful Kabir
Keyword(s):  
Rna Polymerase ◽  
Antiviral Drug ◽  
Antiviral Agent ◽  
Respiratory Illness ◽  
Docking Study ◽  
New Drugs ◽  
Computational Docking ◽  
Recent Success ◽  
Trial Basis ◽  
Docking Calculations

<div>Coronavirus (COVID-19) mediated infection is a highly contagious respiratory illness that was initially found in Wuhan city of Hubei Province in China. The ongoing pandemic of the novel SARS-CoV-2 virus is affecting global health. Despite the recent success in vaccination on a trial basis, there is no treatment of the infection. Thus, establishing an effective therapeutic measure is of apex priority among biologists and healthcare professionals. Re-purposing Remdesivir, a broad-spectrum antiviral agent that inhibits viral RNA polymerase, has been found effective for the treatment of COVID-19. In this study, modification of the existing drug Remdesivir was done. In logical drug designing and development, molecular recognition plays a central role in this sphere. The anti viral function of Remdesivir is achieved by binding to RNA polymerase enzyme. The protein 7BTF is an RNA-dependent RNA polymerase that plays a crucial role in coronavirus replication and transcription machinery and it appears to be the primary target of the antiviral drug Remdesivir. The study intend to design derivative compounds form Remdesivir to screen out the a better drug against the SARS-CoV-2 virus by inhibiting the targeted protein. The efficacy of these new drugs was also tested by molecular docking calculations. The drug derivatives were docked for binding affinity and non-bond interactions. Pharmacokinetic activities of the designed drugs are also predicted. All the drugs are non-carcinogenic and chemically reactive. In our study, modified compound D-I has exhibited the best performance among Remdesivir and it’s derivatives. This study might provide an insight into the potential of a Remdesivir derivative in treating SARS-CoV-2 infection<br></div>

scholarly journals Molecular Docking Study on Some Isonicotinoyl Hydrazide Derivatives as Potential Inhibitors of COVID-19

2020 ◽  
Vol 9 (3) ◽  
pp. 1217-1224
Keyword(s):  
Molecular Docking ◽  
Active Sites ◽  
Antiviral Agent ◽  
Docking Study ◽  
Biologically Active ◽  
New Drugs ◽  
Molecular Docking Study ◽  
Docking Score ◽  
Protease Enzyme ◽  
Potential Inhibitors

Coronavirus (COVID-19) is more than a health disaster;it is the greatest challenge that the world confrontsnowadays. There is a race to slow the spread of this disease. Searching for an antiviral agent to stop COVID-19 is an essential demand since there is no approved drug for COVID-19 till now. Molecular docking is a powerful tool in predicting new drugs. In this study, Favpiravir (Avigan), Hydroxychloroquine, and a series of biologically active compounds derived from iso-nicotinoyl hydrazide have been chosen for molecular docking study. Molecular docking was carried out by theMolegro virtual docker program on proteaseenzyme of COVID-19.The results showed that all the studied molecules are located in the active sites of protease after molecular docking. The tested nicotinoyl hydrazide derivatives showed a higher ranking docking score than Favpiravir (Avigan). According to the docking score ranking rearrangement, Hydroxychloroquine comes the third, and Favpiravir comes the last among the tested compounds. N(2-iso-nicotinoyl hydrazine-carbonthioyl)benzamide(2) and the enol form of (E)-N-(1-phenylethylidene)-nicotinohydrazide(7) have shown the highest docking score (123.23 and -123.12 kcal/mol respectively) among the tested compounds. Ligands (2) and (7) are expected to be potential inhibitors of the main protease enzyme of coronavirus.

scholarly journals An evidence-based systematic review on emerging therapeutic and preventive strategies to treat novel coronavirus (SARS-CoV-2) during an outbreak scenario

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Anupama M. Gudadappanavar ◽  
Jyoti Benni
Keyword(s):  
Antiviral Drug ◽  
Drug Repurposing ◽  
Respiratory Illness ◽  
World Health ◽  
Recombinant Vaccines ◽  
Subunit Vaccines ◽  
Coronavirus Infection ◽  
Novel Coronavirus ◽  
Health Organization ◽  
Full Length Genome

AbstractA novel coronavirus infection coronavirus disease 2019 (COVID-19) emerged from Wuhan, Hubei Province of China, in December 2019 caused by SARS-CoV-2 is believed to be originated from bats in the local wet markets. Later, animal to human and human-to-human transmission of the virus began and resulting in widespread respiratory illness worldwide to around more than 180 countries. The World Health Organization declared this disease as a pandemic in March 2020. There is no clinically approved antiviral drug or vaccine available to be used against COVID-19. Nevertheless, few broad-spectrum antiviral drugs have been studied against COVID-19 in clinical trials with clinical recovery. In the current review, we summarize the morphology and pathogenesis of COVID-19 infection. A strong rational groundwork was made keeping the focus on current development of therapeutic agents and vaccines for SARS-CoV-2. Among the proposed therapeutic regimen, hydroxychloroquine, chloroquine, remdisevir, azithromycin, toclizumab and cromostat mesylate have shown promising results, and limited benefit was seen with lopinavir–ritonavir treatment in hospitalized adult patients with severe COVID-19. Early development of SARS-CoV-2 vaccine started based on the full-length genome analysis of severe acute respiratory syndrome coronavirus. Several subunit vaccines, peptides, nucleic acids, plant-derived, recombinant vaccines are under pipeline. This article concludes and highlights ongoing advances in drug repurposing, therapeutics and vaccines to counter COVID-19, which collectively could enable efforts to halt the pandemic virus infection.

scholarly journals Chikungunya and Zika Viruses: Co-Circulation and the Interplay between Viral Proteins and Host Factors

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 448
Author(s):  
Sineewanlaya Wichit ◽  
Nuttamonpat Gumpangseth ◽  
Rodolphe Hamel ◽  
Sakda Yainoy ◽  
Siwaret Arikit ◽  
...  
Keyword(s):  
Antiviral Drug ◽  
Virus Transmission ◽  
Antiviral Agent ◽  
Viral Proteins ◽  
Targeted Therapeutics ◽  
Limited Information ◽  
Mosquito Vectors ◽  
Host Proteins ◽  
Host Interactions ◽  
Viral Host Interactions

Chikungunya and Zika viruses, both transmitted by mosquito vectors, have globally re-emerged over for the last 60 years and resulted in crucial social and economic concerns. Presently, there is no specific antiviral agent or vaccine against these debilitating viruses. Understanding viral–host interactions is needed to develop targeted therapeutics. However, there is presently limited information in this area. In this review, we start with the updated virology and replication cycle of each virus. Transmission by similar mosquito vectors, frequent co-circulation, and occurrence of co-infection are summarized. Finally, the targeted host proteins/factors used by the viruses are discussed. There is an urgent need to better understand the virus–host interactions that will facilitate antiviral drug development and thus reduce the global burden of infections caused by arboviruses.

Selection of oxypeucedanin as a potential antagonist from molecular docking analysis of HSP90

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Joshua Oluwasegun Bamidele ◽  
George Oche Ambrose ◽  
Oluwaseun Suleiman Alakanse
Keyword(s):  
Molecular Docking ◽  
Liver Toxicity ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Docking Analysis ◽  
Computational Docking ◽  
Drug Candidates ◽  
Expression Rate ◽  
Client Proteins

AbstractHSP90 is observed as one of the copious molecular chaperones that play a key role in mediating appropriate folding, maturation, and firmness of many client proteins in cells. The expression rate of HSP90 in cancer cells is at a level of 2- to 10-fold higher than the 1- to 2-fold of its unstressed and healthy ones. To combat this, several inhibitors to HSP90 protein have been studied (such as geldanamycin and its derivative 17-AAG and 17-DMAG) and have shown some primary side effects including plague, nausea, vomiting, and liver toxicity, hence the search for the best-in-class inhibitor for this protein through in silico. This study is aimed at analyzing the inhibitory potency of oxypeucedanin-a furocoumarin derivations, which have been reported to have antipoliferative activity in human prostrate carcinoma DN145 cells, and three other drug candidates retrieved from the literature via computational docking studies. The results showed oxypeucedanin as the compound with the highest binding energy of −9.2 kcal/mol. The molecular docking study was carried out using PyRx, Auto Dock Vina option, and the target was validated to confirm the proper target and the docking procedure employed for this study.

scholarly journals Back to Nature: Combating Candida albicans Biofilm, Phospholipase and Hemolysin Using Plant Essential Oils

Antibiotics ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 81
Author(s):  
Ahmed M. El-Baz ◽  
Rasha A. Mosbah ◽  
Reham M. Goda ◽  
Basem Mansour ◽  
Taranum Sultana ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Essential Oils ◽  
Docking Study ◽  
New Drugs ◽  
Molecular Docking Study ◽  
Plant Essential Oils ◽  
Force Microscopy ◽  
Atomic Force ◽  
Afm Analysis ◽  
Phenotypic Methods

Candida albicans is the causative agent of fatal systemic candidiasis. Due to limitations of antifungals, new drugs are needed. The anti-virulence effect of plant essential oils (EOs) was evaluated against clinical C. albicans isolates including cinnamon, clove, jasmine and rosemary oils. Biofilm, phospholipase and hemolysin were assessed phenotypically. EOs were evaluated for their anti-virulence activity using phenotypic methods as well as scanning electron microscopy (SEM) and atomic force microscopy (AFM). Among the C. albicans isolates, biofilm, phospholipase and hemolysins were detected in 40.4, 86.5 and 78.8% of isolates, respectively. Jasmine oil showed the highest anti-biofilm activity followed by cinnamon, clove and rosemary oils. SEM and AFM analysis showed reduced adherence and roughness in the presence of EOs. For phospholipase, rosemary oil was the most inhibitory, followed by jasmine, cinnamon and clove oils, and for hemolysins, cinnamon had the highest inhibition followed by jasmine, rosemary and clove oils. A molecular docking study revealed major EO constituents as promising inhibitors of the Als3 adhesive protein, with the highest binding for eugenol, followed by 1,8-cineole, 2-phenylthiolane and cinnamaldehyde. In conclusion, EOs have a promising inhibitory impact on Candida biofilm, phospholipase and hemolysin production, hence EOs could be used as potential antifungals that impact virulence factors.

Determination of binding potential of HCV protease inhibitors against SARS-CoV-2 Papain-like protease with computational docking

2021 ◽  
Vol 18 ◽  
Author(s):  
Zihni Onur Çalışkaner
Keyword(s):  
Protease Inhibitors ◽  
Drug Repurposing ◽  
Docking Study ◽  
Binding Energies ◽  
Binding Potential ◽  
Computational Docking ◽  
In Silico Docking ◽  
Hcv Protease ◽  
Novel Coronavirus ◽  
Inhibitory Molecules

Background: SARS-CoV-2, a novel coronavirus that causes a pandemic respiratory disease, has recently emerged from China. Since it’s a life-threatening virus, investigation of curative medications along with protective vaccines still maintains its importance. Drug repurposing is a reasonable and immediate approach to combat SARS-CoV-2 infection by identifying inhibitory molecules from marketed drugs. PL protease (PLpro.) is one of the essential enzymes for the progression of SARS-CoV-2 replication and life cycle. Objective: We aimed to investigate the potential of 4 HCV protease inhibitors as probable repurposing drugs in Covid-19 treatment. Methods: In order to understand the possible binding affinity of HCV protease inhibitors, Boceprevir, Grazoprevir, Simeprevir, and Telaprevir, against to PLpro, we performed docking analysis in silico. Docking study was accomplished using AutoDock 4.2 software. Potential druggable pockets on PLpro were predicted by DoGSiteScorer tool in order to explore any overlapping with binding regions and these pockets. Results: This analysis demonstrated Boceprevir, Grazoprevir, Simeprevir and Telaprevir interacted by PLpro with binding energies (kcal/mol) of -4.97, -4.24, -6.98, -1.08, respectively. Asn109, one of the interacted residues with both Boceprevir and Simeprevir, is a neighbouring residue to catalytic Cys111. Additionally, Telaprevir notably interacted with catalytic His272 in the active site. Conclusion: Present study explains the binding efficiency and repurposing potential of certain HCV protease inhibitors against to SARS-CoV-2 PLpro enzyme. Docking sites and potential druggability of ligands were also crosschecked by the estimation of druggable pockets. Thereby our results can promote promising preliminary data for research on drug development in the fight of Covid-19.

scholarly journals Beyond members of the Flaviviridae family, sofosbuvir also inhibits chikungunya virus replication

2018 ◽  
Author(s):  
André C. Ferreira ◽  
Patrícia A. Reis ◽  
Caroline S. de Freitas ◽  
Carolina Q. Sacramento ◽  
Lucas Villas Bôas Hoelz ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Chikungunya Virus ◽  
Therapeutic Option ◽  
Antiviral Drug ◽  
Specific Treatment ◽  
Public Health Problem ◽  
Hepatoma Cells ◽  
Dependent Manner ◽  
Mice Model ◽  
Human Hepatoma Cells

AbstractChikungunya virus (CHIKV) causes a febrile disease associated with chronic arthralgia, which may progress to neurological impairment. Chikungunya fever (CF) is a consolidated public health problem, in tropical and subtropical regions of the world, where control of CHIKV vector, mosquitos of theAedesgenus, failed. Since there is no vaccine or specific treatment against CHIKV, infected patients receive only palliative care to alleviate pain and arthralgia. Thus, drug repurposing is necessary to identify antivirals against CHIKV. Recently, the structure and activity of CHIKV RNA polymerase was partially resolved, revealing similar aspects with the enzyme counterparner on other positive sense RNA viruses, such as members of the Flaviviridae family. We then evaluated if sofosbuvir, clinically approved against hepatitis C virus RNA polymerase, which also aims to dengue, Zika and yellow fever viruses replication, would inhibit CHIKV replication. Indeed, sofosbuvir was 5-times more selective in inhibiting CHIKV production in human hepatoma cells than ribavirin, a pan-antiviral drug. Although CHIKV replication in human induced pluripotent stem cell (iPS)-derived astrocytes was less sensitive to sofosbuvir’s, compared to hepatoma cells – this drug still impaired virus production and cell death in a MOI-dependent manner. Sofosbuvir also exhibited antiviral activityin vivo, by preventing CHIKV-induced paw oedeme in adult mice, at 20 mg/kg/day, and mortality on neonate mice model, at 40 and 80 mg/kg/day. Our data demonstrates that a prototypic alphavirus, CHIKV, is also susceptible to sofosbuvir. Since this is a clinically approved drug, it could pave the way to become a therapeutic option against CF.

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