scholarly journals Identification of Dietary Molecules as Therapeutic Agents to Combat COVID-19 Using Molecular Docking Studies

2020 ◽  
Author(s):  
Mohammad Faheem Khan ◽  
Mohsin Ali Khan ◽  
Zaw Ali Khan ◽  
Tanveer Ahamad ◽  
Waseem Ahmad Ansari
Keyword(s):  
Molecular Docking ◽  
Antiviral Agents ◽  
Epigallocatechin Gallate ◽  
World Health Organisation ◽  
Therapeutic Agents ◽  
Binding Energies ◽  
World Health ◽  
Major Constituent ◽  
Drug Candidate ◽  
Health Crisis

Abstract Recently, a new and fatal strain of coronavirus named as SARS-CoV-2 (Disease: COVID-19) appeared in Wuhan, China in December of 2019. Due to its fast growing human to human transmission and confirmed cases in nearly every country, it has been declared as pandemic by World Health Organisation (WHO) on 11 March 2020. Till now, there is no therapy such as vaccines and specific therapeutic agents available globally. Inspite of this, some protease inhibitors and antiviral agents namely lopinavir, ritonavir, remdisivir and chloroquine are under investigation and also implemented in several countries as therapeutic agents for the treatment of COVID-19. Seeing the health crisis across the world, it was our aim to find out a suitable drug candidate which could target SARS-CoV-2. For this purpose, molecular docking of 7 proteinsof SARS-CoV-2 was done with 18active constituents that have previously been reported to be antiviral or anti-SARS-CoV agents. The docking results of these 18 compounds were compared with 2 FDA approved drugs that have are currently being used in COVID 19, namely Remdesivir and Chloroquine. Our result revealed that among all, epigallocatechin gallate (EGCG), a major constituent of green tea, is the lead compound that could fit well into the binding sites of docked proteins of SARS-CoV-2. EGCG showed very strong molecular interactions with binding energies -9.30, -8.66, -8.38, -7.57, -7.26, -6.99 and -4.90 kcal/mole for6y2e, 6vw1, 6vww, 6lxt,6vsb, 6lu7 and 6lvnproteins of SARS-CoV-2, respectively.Therefore, EGCG as per our results, should be explored as a drug candidate for the treatment of COVID-19.

In-Silico Study to Identify Dietary Molecules as Potential SARS-CoV-2 Agents

2020 ◽  
Vol 17 ◽  
Author(s):  
Mohammad Faheem Khan ◽  
Mohsin Ali Khan ◽  
Zaw Ali Khan ◽  
Tanveer Ahamad ◽  
Waseem Ahmad Ansari
Keyword(s):  
Therapeutic Agent ◽  
Virus Disease ◽  
Antiviral Agents ◽  
World Health Organisation ◽  
Therapeutic Agents ◽  
Binding Energies ◽  
World Health ◽  
Therapeutic Drug ◽  
Lipinski’S Rule ◽  
Encoded Proteins

Background:: Recently, Corona Virus Disease-2019 (COVID-19), caused by fatal strain of coronavirus named Severe Acute Respiratory Syndrome-2 (SARS-CoV-2) has been declared as a pandemic by the World Health Organisation (WHO) on 11 March 2020. Globally, no therapy such as vaccines and specific therapeutic agents is available so far despite of some protease inhibitors and antiviral agents. Introduction:: Because of no therapeutic drug or vaccine against SARS-CoV-2 so far, phytomedicine may be developed as therapeutic agents in the prevention and treatment of current COVID-19 disease. Thus, the aim of this study was to find out a suitable therapeutic agent from selected 17 dietary molecules, which could target SARS-CoV-2 encoded proteins. Method:: In this study, 3D structures of selected dietary molecules were obtained from the PubChem database, which have previously reported for their antiviral and anti-inflammatory effects. Then, molecular docking analysis by using AutoDoc4 and AutoDockVina software was conducted to evaluate their anti-SARS-CoV-2 activity. Lipinski’s rule of five and druglikeness properties were also discussed with the help of Molinspiration and the OSIRIS property explorer methods. Results and Discussion:: Our result revealed that among all, epigallocatechin gallate (EGCG) (7) is a lead compound that could fit well into the binding sites of docked proteins of SARS-CoV-2. EGCG showed very strong molecular interactions with the free enzyme of main protease (6y2e), chimeric receptor-binding domain complexed with human ACE2 (6vw1), and NSP15 endoribonuclease (6vww) encoded proteins of SARS-CoV-2, by showing binding energies -9.30, -8.66, and -8.38, kcal/mole respectively. Conclusion:: In the present study, EGCG (7) is more active than three standard drugs that are currently being used in COVID 19, namely remdesivir and nafamostat. Therefore, EGCG (7), as per our results, might be explored as a therapeutic agent for the treatment of COVID-19.

Therapeutic agents for COVID-19: An Overview

2020 ◽  
Vol 15 ◽  
Author(s):  
Sreejan Manna ◽  
Mainak Mal ◽  
Manas Bhowmik ◽  
Dipika Mandal
Keyword(s):  
Clinical Trial ◽  
Antiviral Agents ◽  
Positive Outcome ◽  
Therapeutic Agents ◽  
World Health ◽  
Drug Candidate ◽  
Novel Coronavirus ◽  
Health Organization ◽  
Approved Drugs ◽  
Almost All

Background:: The pathological agent of Coronavirus disease 2019 (COVID-19), is a novel coronavirus termed as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has its origin in Wuhan, China from where it spread to other provinces in China and subsequently to other countries resulting in a pandemic worldwide. The virus is extremely contagious and causes pneumonia and respiratory failure. Since its emergence researchers around the world are trying to develop vaccines and find suitable drugs for the treatment of COVID-19. Objective:: To give an overview of the various therapeutic agents for COVID-19 such as vaccines and drugs that are in preclinical stage or under different stages of clinical trial. Results:: As per World Health Organization (WHO) there are 137 vaccines under development till date out of which few vaccines have successfully completed preclinical studies and reached clinical trial. According to present scenario, to date, only one coronavirus vaccine (sputnik-V) has been approved by the Ministry of Health of the Russian Federation. Till date, there are no United States Food and Drug Administration (USFDA) approved drugs to treat COVID-19 patients. However depending on patient’s condition, different drugs such as antiviral agents like Remdesivir, antimalarial drugs like Hydroxychloroquine, antibiotics like Azithromycin and corticosteroids like Dexamethasone are being applied and some of them have proved to be effective up to certain extent. Conclusion:: Although several vaccines for COVID-19 are under development and various drugs have been tried for its treatment, an ideal drug candidate or a vaccine is still lacking. Almost all the big pharmaceutical companies are associated with one or more research initiatives in order to develop vaccines and drugs. Many of them are going through clinical stages expecting a positive outcome by the end of 2020.

scholarly journals COVID-19: Needs assessment of the pharmacy profession and contributions so far across the Commonwealth

2020 ◽  
Author(s):  
Diane Ashiru-Oredope ◽  
Amy Chan ◽  
Omotayo Olaoye ◽  
Victoria Rutter ◽  
Zaheer-Ud-Din Babar ◽  
...  
Keyword(s):  
World Health Organisation ◽  
World Health ◽  
Learning Needs ◽  
Online Questionnaire ◽  
Health Crisis ◽  
General Anxiety ◽  
The Pacific ◽  
Pharmacy Profession ◽  
The World ◽  
The Impact

Abstract BackgroundThe declaration of COVID-19 a pandemic by the World Health Organisation on the 11March 2020 marked the beginning of a global health crisis of an unprecedented natureand scale. The approach taken by countries across the world varied widely, however,the delivery of frontline healthcare was consistently recognised as being central to thepandemic response. This study aimed to identify and explore the issues currentlyfacing pharmacy teams across Commonwealth countries during the COVID-19pandemic. The study also evaluates pharmacy professionals’ understanding of keyknowledge areas from the COVID-19 webinar hosted by the CommonwealthPharmacists’ Association ( CPA) on 5 th June 2020.MethodA quantitative survey-based approach was adopted, using a 32-item questionnairedeveloped from the literature on pharmacy and pandemic response. The survey washosted on Survey Monkey and pilot tested. The final survey was disseminated by CPAmember organisations. A 6-item online questionnaire was sent via email to allattendees of CPA's COVID-19 webinar. Descriptive statistics on frequency distributionsand percentages were used to analyse the responses. Data were analysed usingMicrosoft® Excel (2010).ResultsThere were 545 responses from pharmacy professionals across 31/54 commonwealthcountries in Africa, Asia, the Americas, Europe and the Pacific. Majority of therespondents reported being at least somewhat worried (90%) and more than 65% werevery worried or extremely about the impact of COVID-19 on them personally andprofessionally. Nearly two-thirds of respondents stated finding it somewhat difficult orvery difficult to work effectively during the pandemic. Challenges mostly faced bypharmacy professionals working remotely included; general anxiety about the impact ofCOVID-19 on their lives (12%), and difficulties in communicating with their co-workers(12%). Most pharmacy professionals had not previously been actively involved in aglobal health emergency (82%) nor obtained training on global/public healthemergency preparedness (62%). Between 45% to 97% of the COVID-19 webinarattendees provided the correct answers to post-webinar questions, suggesting someimprovement in knowledge.ConclusionOur study confirms pharmacy professional’s concerns about practice during apandemic and provides preliminary data on the challenges and learning needs of theprofession. The CPA has since acted on these findings, providing on-goingopportunities to develop and refine resources for the profession as the pandemicevolves. Pharmacy professionals have also demonstrated improved knowledge on themanagement of COVID-19 and resources available for professionals.

Screening of Potent Inhibitors Against 2019 Novel Coronavirus (Covid-19) from Alliumsativum and Allium cepa: An In Silico Approach

2020 ◽  
Vol 11 (1) ◽  
pp. 7981-7993
Keyword(s):  
Molecular Docking ◽  
Allium Cepa ◽  
In Silico ◽  
Treatment Options ◽  
Natural Compounds ◽  
Binding Energies ◽  
Drug Candidate ◽  
Molecular Docking Study ◽  
Standard Drug ◽  
Main Protease

The infection of the global COVID-19 pandemic and the absence of any possible treatment options warrants the use of all available resources to find effective drugs against this scourge. Various ongoing researches have been searching for the new drug candidate against COVID-19 infection. The research objective is based on the molecular docking study of inhibition of the main protease of COVID-19 by natural compounds found in Allium sativum and Allium cepa. Lipinski rule of five and Autodock 4.2 was used by using the Lamarckian Genetic Algorithm to perform Molecular docking to analyze the probability of docking. Further, ADME analysis was also performed by using SwissADME, which is freely available on the web. In the present study, we identified S-Allylcysteine sulfoxide (Alliin), S-Propyl cysteine, S-Allylcysteine, S-Ethylcysteine, S-Allylmercaptocysteine, S-Methylcysteine, S-propyl L-cysteine with binding energies (-5.24, -4.49, -4.99, -4.91, -4.79, -4.76, -5.0 kcal/mol) as potential inhibitor candidates for COVID-19. Out of 7 selected compounds, alliin showed the best binding efficacy with target protein 6LU7. In silico ADME analysis revealed that these compounds are expected to have a standard drug-like property as well. Our findings propose that natural compounds from garlic and onion can be used as potent inhibitors against the main protease of COVID-19, which could be helpful in combating the COVID-19 pandemic.

scholarly journals Molecular Docking and Dynamics Simulation Study of Hyrtios erectus Isolated Scalarane Sesterterpenes as Potential SARS-CoV-2 Dual Target Inhibitors

Biology ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 389
Author(s):  
Sameh S. Elhady ◽  
Reda F. A. Abdelhameed ◽  
Rania T. Malatani ◽  
Abdulrahman M. Alahdal ◽  
Hanin A. Bogari ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Md Simulation ◽  
Protein Complexes ◽  
Antiviral Agents ◽  
Binding Energies ◽  
Dynamics Simulation ◽  
Main Protease ◽  
Simulation Parameters ◽  
Molecular Docking And Dynamics ◽  
Dual Target

Presently, the world is under the toll of pandemic coronavirus disease-2019 (COVID-19) outbreak caused by SARS-CoV-2. Lack of effective and safe therapeutics has stressed the scientific community for developing novel therapeutics capable of alleviating and stopping this pandemic. Within the presented study, molecular docking, ADME properties and all-atom molecular dynamic (MD) simulation, along with two standard antiviral agents (lopinavir and benzopurpurin-4B), were applied to investigate 15 scalaranes sesterterpenes natural compounds, purified from the Red Sea marine sponge Hyrtios erectus, as potential COVID-19 dual-target inhibitors. Following multi-step docking within COVID-19 main protease and Nsp15 endoribonuclease cavities, nine promising drug-like compounds exhibited higher docking scores as well as better interactions with the target’s crucial residues than those of reference ligands. Compounds 2, 6, 11, and 15, were predicted to simultaneously subdue the activity of the two COVID-19 targets. Dynamics behavior of the best-docked molecules, compounds 15 and 6, within COVID-19 target pockets showed substantial stability of ligand-protein complexes as presented via several MD simulation parameters. Furthermore, calculated free-binding energies from MD simulation illustrated significant ligand’s binding affinity towards respective target pockets. All provided findings supported the utility of scalarane-based sesterterpenes, particularly compounds 15 and 6, as promising lead candidates guiding the development of effective therapeutics against SARS-CoV-2.

scholarly journals A threefold approach including quantum chemical, molecular docking and molecular dynamic studies to explore the natural compounds from Centaurea jacea as the potential inhibitors for COVID-19

2023 ◽  
Vol 83 ◽  
Author(s):  
S. Muhammad ◽  
M. F. Maqbool ◽  
A. G. Al-Sehemi ◽  
A. Iqbal ◽  
M. Khan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Molecular Dynamic ◽  
Bioactive Compounds ◽  
Quantum Chemical ◽  
Hydrophobic Interactions ◽  
Binding Energies ◽  
Perennial Herb ◽  
Drug Candidate ◽  
Aqueous Environment ◽  
Centaurea Jacea

Abstract In the current report, we studied the possible inhibitors of COVID-19 from bioactive constituents of Centaurea jacea using a threefold approach consisting of quantum chemical, molecular docking and molecular dynamic techniques. Centaurea jacea is a perennial herb often used in folk medicines of dermatological complaints and fever. Moreover, anticancer, antioxidant, antibacterial and antiviral properties of its bioactive compounds are also reported. The Mpro (Main proteases) was docked with different compounds of Centaurea jacea through molecular docking. All the studied compounds including apigenin, axillarin, Centaureidin, Cirsiliol, Eupatorin and Isokaempferide, show suitable binding affinities to the binding site of SARS-CoV-2 main protease with their binding energies -6.7 kcal/mol, -7.4 kcal/mol, -7.0 kcal/mol, -5.8 kcal/mol, -6.2 kcal/mol and -6.8 kcal/mol, respectively. Among all studied compounds, axillarin was found to have maximum inhibitor efficiency followed by Centaureidin, Isokaempferide, Apigenin, Eupatorin and Cirsiliol. Our results suggested that axillarin binds with the most crucial catalytic residues CYS145 and HIS41 of the Mpro, moreover axillarin shows 5 hydrogen bond interactions and 5 hydrophobic interactions with various residues of Mpro. Furthermore, the molecular dynamic calculations over 60 ns (6×106 femtosecond) time scale also shown significant insights into the binding effects of axillarin with Mpro of SARS-CoV-2 by imitating protein like aqueous environment. From molecular dynamic calculations, the RMSD and RMSF computations indicate the stability and dynamics of the best docked complex in aqueous environment. The ADME properties and toxicity prediction analysis of axillarin also recommended it as safe drug candidate. Further, in vivo and in vitro investigations are essential to ensure the anti SARS-CoV-2 activity of all bioactive compounds particularly axillarin to encourage preventive use of Centaurea jacea against COVID-19 infections.

scholarly journals A potential spice with multifunctional pharmacological properties can prevent COVID-19 disease

2021 ◽  
Vol 9 (6) ◽  
pp. 1840
Author(s):  
Subha Bose Banerjee
Keyword(s):  
Wide Spectrum ◽  
World Health Organisation ◽  
World Health ◽  
Replication Process ◽  
Health Crisis ◽  
Therapeutic Drugs ◽  
Global Pandemic ◽  
Therapeutic Properties ◽  
Novel Coronavirus ◽  
Pharmacologically Active

Novel coronavirus disease (COVID-19) is the major health crisis in the world. World Health Organisation has declared COVID-19 as a global pandemic. There are no effective drugs to treat COVID-19 infection. Till date include remdesivir, umifenovir, favipiravir, lopinavir/ritonavir, ribavirin, hydroxychloroquine, etc. are used to treat this disease. There is an urgent need for public health measures, not only to limit the spread of the virus, but also to implement preventive approaches to control severe COVID-19 disease. Most drugs on the market have shown unwanted symptoms and toxic effects related to these drugs. In this situation people are searching for safe herbal extracts and pharmacologically active molecules having numerous therapeutic properties. Garlic (Allium sativum L.; Family: Amaryllidaceae) is an aromatic herbaceous annual spice with numerous therapeutic properties. Garlic is one of the most efficient natural antibiotics against the wide spectrum of viruses and bacteria. Organosulfur (e.g. allicin and alliin) and flavonoid (e.g. quercetin) compounds are responsible for immunomodulatory effects of this healthy spice. The viral replication process is accelerated with the main structural protease of severe acute respiratory syndrome corona virus-2 (SARS-CoV-2). The formation of hydrogen bonds between this serine-type protease and garlic bioactives in the active site regions inhibits the COVID-19 outbreak. Intake of garlic and its derived-products in regular diet as an adjuvant therapy may minimise side effects and toxicity of the main therapeutic drugs of COVID-19 infection.

scholarly journals Molecular Docking Study of Quercetein Analogues for Treating Tumours

2019 ◽  
Vol 12 (4) ◽  
pp. 30-34
Author(s):  
S. Gejalakshmi ◽  
N. Harikrishnan
Keyword(s):  
Molecular Docking ◽  
Drug Discovery ◽  
Structural Diversity ◽  
Docking Study ◽  
Therapeutic Agents ◽  
Drug Candidate ◽  
Molecular Docking Study ◽  
Drug Candidates ◽  
Drug Compounds ◽  
Scientific Task

Drug discovery leading to robust and viable lead candidate’s remains a challenging scientific task, which is the transition from a screening hit to a drug candidate, requires expertise and experience. Natural products and their derivatives have been recognized for many years as a source of therapeutic agents and of structural diversity. The present research attempts to describe the utilization of compounds derived from natural resources as drug candidates, with a focus on the success of these resources in the process of finding and discovering new and effective drug compounds, an approach commonly referred to as ―natural product drug discovery

scholarly journals Natural xanthone compounds as promising drug candidates against COVID-19 - An integrated molecular docking and dynamics simulation study

2020 ◽  
Author(s):  
Shravan Kumar Gunda ◽  
Hima Kumari P ◽  
Gourav Choudhir ◽  
Anuj Kumar ◽  
P B. Kavi Kishor ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antiviral Agents ◽  
Binding Energies ◽  
Dynamics Simulation ◽  
Lipinski’S Rule ◽  
Drug Candidates ◽  
Main Protease ◽  
Lipinski’S Rule Of Five ◽  
Dynamics Simulations ◽  
Potential Inhibitors

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease2019 (COVID-19). SARS-CoV-2 is known for its high pathogenicity and transmission due to thepresence of polybasic cleavage sites. No specific drug is available for the treatment. To identifythe potential inhibitors, we have performed molecular docking against the SARS-CoV-2 mainprotease (6Y84) with fifteen important natural xanthone compounds. The docking results showedall the compounds exhibited good binding energies and interactions with the main protease. Thevalidation of representative docking complexes through molecular dynamics simulations showedthat xanthones binds with a higher binding affinity and lower free energy than the standardligand with Brasixanthone C and Brasixanthone B on 50 ns. Natural xanthone compounds havealso passed the Absorption, Distribution, Metabolism, and Excretion (ADME) property criteriaas well as Lipinski’s rule of five. The present integrated molecular docking and dynamicssimulations study unveil the use of xanthones as potential antiviral agents against SARS-CoV-2.

scholarly journals Molecular Docking Analysis of Chloroquine and Hydroxychloroquine and Design of Anti-SARS-CoV2 Protease Inhibitor

2020 ◽  
Vol 14 (10) ◽  
pp. 52
Author(s):  
Usman Abdulfatai ◽  
Adamu Uzairu ◽  
Gideon Adamu Shallangwa ◽  
Sani Uba
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Binding Energy ◽  
Binding Site ◽  
Docking Simulation ◽  
Binding Energies ◽  
Drug Candidate ◽  
Molecular Docking Study ◽  
Docking Analysis ◽  
Molecular Docking Analysis

In this present investigation, simulated molecular docking study of chloroquine and hydroxychloroquine compounds were investigated on the SARS-CoV2 enzyme to determine the types of amino acids responsible for the biochemical reaction at the binding site. A structure-based docking design technique was explored in designing a novel derivative of chloroquine for the treatment and management of new COVID 19 disease. To achieve this, the molecular docking simulation method was used to investigate the level of chloroquine and hydroxychloroquine (Drugs presently under clinical trial) interactions on SARS-CoV2 enzyme (a causative agent of COVID 19 disease). Chloroquine and hydroxychloroquine which has been debated as drugs for the management of COVID 19 were subjected to molecular docking analysis, and the binding energies generated were found to be -6.1 kcal/mol and -6.8 kcal/mol respectively. Moreover, novel 2-((4-((7-chloroquinolin-4 yl) amino)pentyl)((methylamino)methyl)amino) ethan-1-ol as an anti-SARS-CoV2 protease was designed through the structural modification of hydroxychloroquine. The binding energy of this drug candidate was found to be -6.9 kcal/mol. This novel drug was found to formed hydrogen and conventional interactions with the binding site of SARS-CoV2 protease through amino acids such as Glutamic acid (GLU166), Glycine (GLY143), Phenylalanine (PHE140), Asparagine (ASN142), Histidine (HIS163), His (HIS172, HIS41, HIS163), Leucine (LEU41, LEU27), Glycine (GLY143), Glutamine (GLN189), Methionine (MET49, MET165), Serine (SER 46), Cysteine (CYS145) and Threonine (THR25). With this binding energy, this new drug candidate could bind better to the human SARS-CoV2 protease’ binding site. This research provides a clue for other scientists on various ways of designing and identify the types of amino acids that may be responsible for biochemical action on SARS-CoV2 protease.

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