scholarly journals Exploring the SARS-CoV-2 Proteome in the Search of Potential Inhibitors via Structure-Based Pharmacophore Modeling/Docking Approach

Computation ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 77
Author(s):  
Giulia Culletta ◽  
Maria Rita Gulotta ◽  
Ugo Perricone ◽  
Maria Zappalà ◽  
Anna Maria Almerico ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Drug Repurposing ◽  
Pharmacophore Modeling ◽  
World Health ◽  
Quality Model ◽  
Experimental Drugs ◽  
Docking Approach ◽  
Health Organization ◽  
Potential Inhibitors ◽  
Pharmacophore Models

To date, SARS-CoV-2 infectious disease, named COVID-19 by the World Health Organization (WHO) in February 2020, has caused millions of infections and hundreds of thousands of deaths. Despite the scientific community efforts, there are currently no approved therapies for treating this coronavirus infection. The process of new drug development is expensive and time-consuming, so that drug repurposing may be the ideal solution to fight the pandemic. In this paper, we selected the proteins encoded by SARS-CoV-2 and using homology modeling we identified the high-quality model of proteins. A structure-based pharmacophore modeling study was performed to identify the pharmacophore features for each target. The pharmacophore models were then used to perform a virtual screening against the DrugBank library (investigational, approved and experimental drugs). Potential inhibitors were identified for each target using XP docking and induced fit docking. MM-GBSA was also performed to better prioritize potential inhibitors. This study will provide new important comprehension of the crucial binding hot spots usable for further studies on COVID-19. Our results can be used to guide supervised virtual screening of large commercially available libraries.

scholarly journals ABBV-744 as a potential inhibitor of SARS-CoV-2 main protease enzyme against COVID-19

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zeynab Fakhar ◽  
Shama Khan ◽  
Suliman Y. AlOmar ◽  
Afrah Alkhuriji ◽  
Aijaz Ahmad
Keyword(s):  
Virtual Screening ◽  
Drug Repurposing ◽  
Pharmacophore Modeling ◽  
Binding Energies ◽  
Active Inhibitor ◽  
Lead Compounds ◽  
Protease Enzyme ◽  
Main Protease ◽  
Dynamics Simulations ◽  
Potential Inhibitors

AbstractA new pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide and become pandemic with thousands new deaths and infected cases globally. To address coronavirus disease (COVID-19), currently no effective drug or vaccine is available. This necessity motivated us to explore potential lead compounds by considering drug repurposing approach targeting main protease (Mpro) enzyme of SARS-CoV-2. This enzyme considered to be an attractive drug target as it contributes significantly in mediating viral replication and transcription. Herein, comprehensive computational investigations were performed to identify potential inhibitors of SARS-CoV-2 Mpro enzyme. The structure-based pharmacophore modeling was developed based on the co-crystallized structure of the enzyme with its biological active inhibitor. The generated hypotheses were applied for virtual screening based PhaseScore. Docking based virtual screening workflow was used to generate hit compounds using HTVS, SP and XP based Glide GScore. The pharmacological and physicochemical properties of the selected lead compounds were characterized using ADMET. Molecular dynamics simulations were performed to explore the binding affinities of the considered lead compounds. Binding energies revealed that compound ABBV-744 binds to the Mpro with strong affinity (ΔGbind −45.43 kcal/mol), and the complex is more stable in comparison with other protein–ligand complexes. Our study classified three best compounds which could be considered as promising inhibitors against main protease SARS-CoV-2 virus.

scholarly journals ABBV-744 and Onalespid as Potential Inhibitors of SARS-CoV-2 main Protease Enzyme: A Promising Therapeutics in COVID-19?

2020 ◽  
Author(s):  
Zeynab Fakhar ◽  
Shama Khan ◽  
Aijaz Ahmad
Keyword(s):  
Virtual Screening ◽  
Drug Repurposing ◽  
Pharmacophore Modeling ◽  
Binding Studies ◽  
Active Inhibitor ◽  
Lead Compounds ◽  
Protease Enzyme ◽  
Main Protease ◽  
Dynamics Simulations ◽  
Potential Inhibitors

Abstract A new pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide and become pandemic with thousands new deaths and infected cases globally. To address coronavirus disease (COVID-19), currently no effective drug or vaccine is available. This necessity motivated us to explore potential lead compounds by considering drug repurposing approach targeting main protease (Mpro) enzyme of SARS-CoV-2. This enzyme considered to be an attractive drug target as it contributes significantly in mediating viral replication and transcription. Herein, comprehensive computational investigations were performed to identify potential inhibitors of SARS-CoV-2 Mpro enzyme. The structure-based pharmacophore modeling was developed based on the co-crystallized structure of the enzyme with its biological active inhibitor. The generated hypotheses were applied for virtual screening based PhaseScore. Docking based virtual screening work-flow was used to generate hit compounds using HTVS, SP and XP based Glide GScore. The pharmacological and physicochemical properties of the best hit compounds were characterized using ADMET. Molecular dynamics simulations were performed to explore the binding affinities of the considered compounds. Binding studies revealed that compound ABBV-744 binds to the Mpro with strong affinity (Gbind -45.43 kcal/mol), and the complex is more stable in comparison with other protein-ligand complexes. Our study classified three best compounds which could be considered as promising inhibitors against main protease SARS-CoV-2 virus.

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 Virtual Screening of Leishmanial Pyridoxal Kinase Enzyme Inhibitors by Repurposed Anti-Trypanosomal Libraries Reveals Two Core Scaffolds

2020 ◽  
Author(s):  
sanad alfadhel
Keyword(s):  
Virtual Screening ◽  
World Health Organization ◽  
Enzyme Inhibitors ◽  
World Health ◽  
Newly Diagnosed ◽  
Pyridoxal Kinase ◽  
The World ◽  
Protozoal Infection ◽  
Health Organization ◽  
Toxic Drugs

Leishmania is an intracellular protozoal infection, and it is classified as a neglected disease by the World Health Organization (WHO). Annually more than 2 million newly diagnosed cases were treated with highly toxic drugs. Leishmanial pyridoxal kinase enzyme (LPDxK) is an essential and druggable target. DNDI1103666 is the most promising lead as a potential inhibitor for LPDxK

scholarly journals COVID-19 Drug Discovery Using Intensive Approaches

2020 ◽  
Vol 21 (8) ◽  
pp. 2839 ◽  
Author(s):  
Ayumu Asai ◽  
Masamitsu Konno ◽  
Miyuki Ozaki ◽  
Chihiro Otsuka ◽  
Andrea Vecchione ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Rna Viruses ◽  
Drug Repurposing ◽  
Global Scale ◽  
Therapeutic Agents ◽  
Clinical Development ◽  
World Health ◽  
Antiviral Therapies ◽  
The World ◽  
Health Organization

Since the infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in China during December 2019, the coronavirus disease 2019 (COVID-19) has spread on a global scale, causing the World Health Organization (WHO) to issue a warning. While novel vaccines and drugs that target SARS-CoV-2 are under development, this review provides information on therapeutics which are under clinical trials or are proposed to antagonize SARS-CoV-2. Based on the information gained from the responses to other RNA coronaviruses, including the strains that cause severe acute respiratory syndrome (SARS)-coronaviruses and Middle East respiratory syndrome (MERS), drug repurposing might be a viable strategy. Since several antiviral therapies can inhibit viral replication cycles or relieve symptoms, mechanisms unique to RNA viruses will be important for the clinical development of antivirals against SARS-CoV-2. Given that several currently marketed drugs may be efficient therapeutic agents for severe COVID-19 cases, they may be beneficial for future viral pandemics and other infections caused by RNA viruses when standard treatments are unavailable.

scholarly journals Amodiaquine as COVID-19 Mpro Inhibitor: A Theoretical Study

2020 ◽  
Author(s):  
bnacharya Acharya
Keyword(s):  
Molecular Docking ◽  
Theoretical Study ◽  
Pharmacophore Modeling ◽  
World Health ◽  
Clinical Tests ◽  
Therapeutic Approaches ◽  
Global Pandemic ◽  
Screening And Identification ◽  
Health Organization ◽  
Approved Drugs

<div> <div> <div> <p>COVID-19 is caused by severe respiratory syndrome –coronavirus 2 (SARS CoV-2). This has been declared as a global pandemic by World Health Organization (WHO). Currently only supportive care is available for treatment of patients. However availability of direct therapeutic approaches would greatly benefit the patient care and reduce death among COVID- 19 patients. Repurposing of approved drugs against COVID-19 would be a faster method to identify direct therapeutics against COVID-19. This study describes screening and identification of Amodiaquine a known antimalarial as COVID-19 Mpro inhibitor by pharmacophore modeling and molecular docking. Amodiaquine may be repurposed as COVID-19 drug after thorough clinical tests. </p> </div> </div> </div>

scholarly journals Insights on Epidemiology, Pathogenesis, Diagnosis and Possible Treatment of COVID-19 infection

2020 ◽  
Author(s):  
SHASHANK KUMAR MAURYA ◽  
Amit Bhattacharya ◽  
Pooja Shukla ◽  
RAJNIKANT MISHRA
Keyword(s):  
Drug Repurposing ◽  
Review Article ◽  
World Health ◽  
Specific Drug ◽  
Clinical Practices ◽  
Indian Government ◽  
The World ◽  
Health Organization ◽  
And Control ◽  
Primary Transmission

COVID-19, SARS-CoV-2 virus of the coronavirus family, created worldwide infectious outbreak affecting millions of people across the globe showing mild to severe symptoms of pneumonia and acute respiratory distress. Absence of precise information on primary transmission, diagnosis, prognosis, and therapeutics for patients with COVID-19 makes prevention and control tough. Treatment of millions of COVID19 patients without any specific drug is one of the biggest challenge, many existing antiviral drugs are in use as an alternative treatment and hunting is still on the way to develop COVID19 specific drug and vaccine. Being the world second largest populated country, fluctuating climatic condition at every 4 months, India is also at the high risk for spread of COVID19 infection. This review article has been intended to discuss biology of COVID-19, mechanism of COVID-19 infection in humans, epidemiology, possible effect of COVID19 infection on pregnancy, nervous system, individuals diabetes and cardiovascular disease, drug repurposing strategy as an alternative line of treatment and clinical practices recommended by World Health Organization (WHO) and other government agencies followed by situation and measures taken by Indian government to minimize the spread of COVID19 in India.

scholarly journals Computational Molecular Docking and Virtual Screening Revealed Promising SARS-CoV-2 Drugs

2020 ◽  
Author(s):  
Maryam Hosseini ◽  
Wanqiu Chen ◽  
Charles Wang
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Virtual Screening ◽  
Clinical Studies ◽  
Inhibitory Effect ◽  
Docking Approach ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Potential Inhibitors ◽  
Computational Molecular Docking

The pandemic of novel coronavirus disease 2019 (COVID-19) is rampaging the world with more than 1.4 million of confirmed cases and more than 85,000 of deaths across world by April 9th, 2020. There is an urgent need to identify effective drugs to fight against the virus. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the family of coronaviruses consisting of four structural and 16 non-structured proteins. Three non-structural proteins such as main protease, papain like protease, and RNA-dependent RNA polymerase are believed to play a crucial role in the virus replication. We applied a computational ligand-receptor binding modeling and performed a comprehensive virtual screening on the FDA-approved drugs against these three SARS-CoV-2 proteins using AutoDock Vina. Our computational studies indicated that Simeprevir, Ledipasvir, Idarubicin, Saquinavir, Ledipasivir, Partitaprevir, Glecaprevir, and Velpatasvir are all promising inhibitors, which displayed a lower binding energy (higher inhibitory effect) than Remdesivir, Lopinavir, and Ritonavir. However, we found that chloroquine and hydroxychloroquine, which showed efficacy in treating the COVID-19 in recent clinical studies, had high binding energy with all three proteins, suggesting they may work through a different mechanism. We also identified several novel drugs as potential inhibitors against SARS-CoV-2, including antiviral Raltegravir; antidiabetic Amaryl; antibiotics Retapamulin, Rifimixin, and Rifabutin; antiemetic Fosaprepitant and Netupitant. In summary, our computational molecular docking approach and virtual screening identified some promising candidate SARS-CoV-2 drugs that may be considered for further clinical studies.

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