scholarly journals Efficiency Improvements and Discovery of New Substrates for a SARS-CoV-2 Main Protease FRET Assay

2021 ◽  
Author(s):  
Tonko Dražić ◽  
Nikos Kühl ◽  
Mila M. Leuthold ◽  
Mira A. M. Behnam ◽  
Christian D. Klein
Keyword(s):  
Antiviral Drugs ◽  
Biochemical Assay ◽  
Assay Procedure ◽  
Pharmacological Targets ◽  
Main Protease ◽  
Assay Performance ◽  
The World ◽  
Huge Impact ◽  
Assay Protocol ◽  
Fret Pair

ABSTRACTThe COVID-19 pandemic, caused by the SARS-CoV-2 virus, has a huge impact on the world. Although several vaccines have recently reached the market, the development of specific antiviral drugs against SARS-CoV-2 is an important additional strategy in fighting the pandemic. One of the most promising pharmacological targets is the viral main protease (Mpro). Here, we present an optimized biochemical assay procedure for SARS-CoV-2 Mpro. We have comprehensively investigated the influence of different buffer components and conditions on the assay performance, and characterized six FRET substrates with a 2-Abz/Tyr(3-NO2) FRET pair. The substrates 2-AbzSAVLQSGTyr(3-NO2)R-OH, a truncated version of the established DABCYL/EDANS FRET substrate, and a new substrate 2-AbzVVTLQSGTyr(3-NO2)R-OH are promising candidates for screening and inhibitor characterization. In the latter substrate, the incorporation of Val at the position P5 improved the catalytic efficacy. Based on the obtained results, we present here a reproducible, reliable assay protocol using highly affordable buffer components.

scholarly journals Efficiency Improvements and Discovery of New Substrates for a SARS-CoV-2 Main Protease FRET Assay

2021 ◽  
pp. 247255522110206
Author(s):  
Tonko Dražić ◽  
Nikos Kühl ◽  
Mila M. Leuthold ◽  
Mira A. M. Behnam ◽  
Christian D. Klein
Keyword(s):  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Catalytic Efficiency ◽  
Assay Procedure ◽  
Pharmacological Targets ◽  
Main Protease ◽  
Assay Performance ◽  
The World ◽  
Huge Impact ◽  
Assay Protocol

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has a huge impact on the world. Although several vaccines have recently reached the market, the development of specific antiviral drugs against SARS-CoV-2 is an important additional strategy in fighting the pandemic. One of the most promising pharmacological targets is the viral main protease (Mpro). Here, we present an optimized biochemical assay procedure for SARS-CoV-2 Mpro. We have comprehensively investigated the influence of different buffer components and conditions on the assay performance and characterized Förster resonance energy transfer (FRET) substrates with a preference for 2-Abz/Tyr(3-NO2) FRET pairs. The substrates 2-AbzSAVLQSGTyr(3-NO2)R-OH, a truncated version of the established DABCYL/EDANS FRET substrate, and 2-AbzVVTLQSGTyr(3-NO2)R-OH are promising candidates for screening and inhibitor characterization. In the latter substrate, the incorporation of Val at position P5 improved the catalytic efficiency. Based on the obtained results, we present here a reproducible, reliable assay protocol using highly affordable buffer components.

scholarly journals Rapid structure-based identification of potential SARS-CoV-2 main protease inhibitors

2021 ◽  
Author(s):  
M Elizabeth Sobhia ◽  
G Siva Kumar ◽  
Srikanth Sivangula ◽  
Ketan Ghosh ◽  
Harmanpreet Singh ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Natural Product ◽  
Protease Inhibitors ◽  
High Throughput ◽  
Data Bank ◽  
Antiviral Drugs ◽  
Combinatorial Structure ◽  
Main Protease ◽  
The World

The COVID-19 outbreak has thrown the world into an unprecedented crisis. It has posed a challenge to scientists around the globe who are working tirelessly to combat this pandemic. We herein report a set of molecules that may serve as possible inhibitors of the SARS-CoV-2 main protease. To identify these molecules, we followed a combinatorial structure-based strategy, which includes high-throughput virtual screening, molecular docking and WaterMap calculations. The study was carried out using Protein Data Bank structures 5R82 and 6Y2G. DrugBank, Enamine, Natural product and Specs databases, along with a few known antiviral drugs, were used for the screening. WaterMap analysis aided in the recognition of high-potential molecules that can efficiently displace binding-site waters. This study may help the discovery and development of antiviral drugs against SARS-CoV-2.

Comparative docking of SARS-CoV-2 receptors antagonists from repurposing drugs

2020 ◽  
Author(s):  
Micael Davi Lima de Oliveira ◽  
Kelson Mota Teixeira de Oliveira
Keyword(s):  
World Health Organisation ◽  
World Health ◽  
Lung Cells ◽  
The Novel ◽  
High Modulation ◽  
Main Protease ◽  
The World ◽  
Novel Coronavirus ◽  
Viral Receptors ◽  
Theoretical Results

According to the World Health Organisation, until 16 June, 2020, the number of confirmed and notified cases of COVID-19 has already exceeded 7.9 million with approximately 434 thousand deaths worldwide. This research aimed to find repurposing antagonists, that may inhibit the activity of the main protease (Mpro) of the SARS-CoV-2 virus, as well as partially modulate the ACE2 receptors largely found in lung cells, and reduce viral replication by inhibiting Nsp12 RNA polymerase. Docking molecular simulations were performed among a total of 60 structures, most of all, published in the literature against the novel coronavirus. The theoretical results indicated that, in comparative terms, paritaprevir, ivermectin, ledipasvir, and simeprevir, are among the most theoretical promising drugs in remission of symptoms from the disease. Furthermore, also corroborate indinavir to the high modulation in viral receptors. The second group of promising drugs includes remdesivir and azithromycin. The repurposing drugs HCQ and chloroquine were not effective in comparative terms to other drugs, as monotherapies, against SARS-CoV-2 infection.

The chronicle of COVID-19: possible strategies to curb the pandemic

2020 ◽  
Vol 27 ◽  
Author(s):  
Rajesh Kumar ◽  
Seetha Harilal ◽  
Abdullah G. Al-Sehemi ◽  
Githa Elizabeth Mathew ◽  
Simone Carradori ◽  
...  
Keyword(s):  
Life Cycle ◽  
Research And Development ◽  
Vaccine Development ◽  
Therapeutic Strategies ◽  
Antiviral Drugs ◽  
Limited Data ◽  
Social Distancing ◽  
The World ◽  
Novel Virus ◽  
Day By Day

: COVID-19, an epidemic that emerged in Wuhan, has become a pandemic affecting worldwide and is in a rapidly evolving condition. Day by day, the confirmed cases and deaths are increasing many folds. SARS-CoV-2 is a novel virus; therefore, limited data are available to curb the disease. Epidemiological approaches, isolation, quarantine, social distancing, lockdown, and curfew are being employed to halt the spread of the disease. Individual and joint efforts all over the world are producing a wealth of data and information which are expected to produce therapeutic strategies against COVID-19. Current research focuses on the utilization of antiviral drugs, repurposing strategies, vaccine development as well as basic to advanced research about the organism and the infection. The review focuses on the life cycle, targets, and possible therapeutic strategies, which can lead to further research and development of COVID-19 therapy.

Identification of Main Protease of Coronavirus SARS-CoV-2 (Mpro)Inhibitors from Melissa officinalis

2020 ◽  
Vol 17 ◽  
Author(s):  
Olusola O. Elekofehinti ◽  
Opeyemi Iwaloye ◽  
Courage D. Famusiwa ◽  
Olanrewaju Akinseye ◽  
Joao B. T. Rocha
Keyword(s):  
Qsar Model ◽  
Computational Approach ◽  
Melissa Officinalis ◽  
Lead Compounds ◽  
Main Protease ◽  
The World ◽  
Recent Outbreak ◽  
Global Concern ◽  
Catalytic Dyad ◽  
Potential Therapeutic Intervention

Background: he recent outbreak of Coronavirus SARS-CoV-2 (Covid-19) which has rapidly spread around the world in about three months with tens of thousands of deaths recorded so far is a global concern. An urgent need for potential therapeutic intervention is of necessity. Mpro is an attractive druggable target for the development of anti-COVID-19 drug development. Compounds previously characterized from Melissa officinalis were queried against main protease of coronavirus SARS-CoV-2 using computational approach. Results: Melitric acid A and salvanolic acid A had higher affinity than lopinavir and ivermectin using both AutodockVina and XP docking algorithms. The computational approach was employed in the generation of QSAR model using automated QSAR, and in the docking of ligands from Melissa officinalis with SARS-CoV-2 Mpro inhibitors. The best model obtained was KPLS_Radial_28 (R2 = 0.8548 and Q2=0.6474, and was used in predicting the bioactivity of the lead compounds. Molecular mechanics based MM-GBSA confirmed salvanolic acid A as the compound with the highest free energy and predicted bioactivity of 4.777; it interacted with His-41 of the catalytic dyad (Cys145-His41) of SARS-CoV-2 main protease (Mpro), as this may hinder the cutting of inactive viral protein into active ones capable of replication. Conclusion: Salvanolic acid A can be further evaluated as potential Mpro inhibitor.

scholarly journals Laws and Emerging Technologies

Laws ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 46
Author(s):  
Esther Salmerón-Manzano
Keyword(s):  
Information Technologies ◽  
New Technologies ◽  
Legal Issues ◽  
The Other ◽  
Special Issue ◽  
Legal Challenges ◽  
The World ◽  
Huge Impact ◽  
New Challenges ◽  
The Way

New technologies and so-called communication and information technologies are transforming our society, the way in which we relate to each other, and the way we understand the world. By a wider extension, they are also influencing the world of law. That is why technologies will have a huge impact on society in the coming years and will bring new challenges and legal challenges to the legal sector worldwide. On the other hand, the new communications era also brings many new legal issues such as those derived from e-commerce and payment services, intellectual property, or the problems derived from the use of new technologies by young people. This will undoubtedly affect the development, evolution, and understanding of law. This Special Issue has become this window into the new challenges of law in relation to new technologies.

Southeast Asian Muslim Washathyyah in the Global Era

2015 ◽  
Vol 4 (1) ◽  
pp. 137-154
Author(s):  
Syahrin Harahap
Keyword(s):  
Southeast Asia ◽  
Significant Contribution ◽  
Main Idea ◽  
Global Village ◽  
Global Era ◽  
The People ◽  
The World ◽  
Huge Impact ◽  
Religious Aspects ◽  
The Universe

Globalization in the world has given the huge impact on the people, as the new condition of the world has brought the world to the globalism- a consciousness and understanding that the world is one. Globalization has also unified the people in a global village that covers all aspects of life such as economic, political, cultural, religious aspects. This paper will explore the concept of wa¡a¯iyyah which stresses on the moderation and accommodative way and its implementation in Southeast Asia. The main idea of the wa¡a¯iyyah or moderation in religious life is that it offers the importance of realizing the concept of Islamic blessing for all the Universe (Islam; Ra¥matan lil ±lam³n). Therefore, the main offer of the Muslim wa¡a¯iyyah movement is to focus on developing civilization, freedom, justice, prosperity and better future for all the people. It is the main capital of the Wa¡a¯iyyah in Southeast Asia to give the significant contribution to the globalization of the world.

scholarly journals The Rise of Container Tonnage and Port Developments in East Asia

2015 ◽  
Vol 1 (2) ◽  
pp. 189 ◽  
Author(s):  
Mariner Wang
Keyword(s):  
Economic Growth ◽  
International Trade ◽  
East Asia ◽  
Container Terminals ◽  
The World ◽  
Substantial Investment ◽  
Huge Impact

1990’s saw the robust expansion of international trade in East Asia generating a remarkable record high and sustained economic growth unmatched by any other region in the world. In line with this, container tonnage in the region has been ever increased annually. In light of this, the governments in the main ports of the region have plunged substantial investment in expanding and developing new container terminals to cope with the ever increased cargoes out/to the region. Though Lehman Shock in 2008 has given a huge impact on the container volumes in Asia, ports in the East Asia are seen to continue to handle the lion’s share of global container business. In 2013, the container throughput of East Asia accounted for 51.2 per cent out of that of the world, becoming the world container center.

scholarly journals A Computational and Literature-Based Evaluation for a Combination of Chiral Anti-CoV Drugs to Block and Eliminate SARS-CoV-2 Safely

2021 ◽  
Author(s):  
Mohd. Suhail
Keyword(s):  
Side Effects ◽  
Jc Virus ◽  
Computational Study ◽  
Human Cells ◽  
The Body ◽  
Binding Affinities ◽  
Chiral Drugs ◽  
Main Protease ◽  
The World ◽  
Second Wave

<p><a>It has been a great challenge for scientists to develop an anti-covid drug/vaccine with fewer side effects, since the coronavirus began. Of course, the prescription of chiral drugs (chloroquine or hydroxychloroquine) has been proved wrong because these chiral drugs neither kill the virus nor eliminate it from the body, but block SARS-CoV-2 from binding to human cells. Another hurdle in front of the world, is not only the positive test of the patient recovered from coronavirus but also the second wave of Covid 19. Hence, the word demands such a drug or drug combination which not only prevents the entry of SARS-CoV-2 in the human cell but also eliminates it or its material from the body completely. The presented computational study explains (i) why the prescription of chiral drugs was not satisfactory (ii) what types of modification can make their prescription satisfactory (iii) the mechanism of action of chiral drugs (chloroquine and hydroxychloroquine) to block SARS-CoV-2 from binding to human cells, and (iv) the strength of mefloquine to eliminate SARS-CoV-2. As the main protease (M<b><sup>pro</sup></b>) of microbes is considered as an effective target for drug design and development, the binding affinities of mefloquine with the main proteases (M<sup>pros</sup>) of JC virus and SARS-CoV-2, were calculated, and then compared to know the eliminating strength of mefloquine against SARS-CoV-2. The main protease (M<sup>pro</sup>) of JC virus was taken because mefloquine has already shown a tremendous result of eliminating it from the body. The current study includes the docking results and literature data in support of the prescription of a combination of S-(+)-hydroxychloroquine and (+) mefloquine. Besides, the presented study also confirms that the prescription of only hydroxychloroquine would not be so effective as in combined form with mefloquine.</a></p>

scholarly journals Neuroprotective Effects, Biological Activities and Therapeutic Potential of Phytochemicals: A Comprehensive Review

2020 ◽  
pp. 1-11
Author(s):  
Xi-jun Wang ◽  
Shi Qiu ◽  
Aihua Zhang ◽  
Jian-hua Miao ◽  
Hui Sun ◽  
...  
Keyword(s):  
Natural Products ◽  
Neurological Disorders ◽  
Chemical Biology ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Therapeutic Agents ◽  
Neuroprotective Effects ◽  
Alternative Medicines ◽  
Pharmacological Targets ◽  
The World

The incidence of neurological disorders is growing in the world together with an increased lifespan. Nowadays, there are still no effective treatments for neurodegenerative pathology, which make necessary to search for new therapeutic agents. Natural products, most of them used in phytochemicals from herbal medicine, are considered promising alternatives for the treatment of neurodegenerative diseases. Numerous herbs have been applied to neurodegenerative disease treatments as complementary and alternative medicines. In the 21st century, omics-coupled functional pharmacology was developed for neurodegenerative drug discovery from natural products. In this article, we firstly provide the latest understanding of neurological disorders on risk factors, category, diagnosis and treatment, and then specially present an overview of natural products in neuroprotective effects research from chemical biology to pharmacological targets, and also discuss the natural products application and future challenge.

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