150 results match your criteria plpro enzyme

Structural Insight into the Binding of Cyanovirin-N with the Spike Glycoprotein, M and PL of SARS-CoV-2: Protein-Protein Interactions, Dynamics Simulations and Free Energy Calculations.

Molecules 2021 Aug 24;26(17). Epub 2021 Aug 24.

Centre for Algal Biotechnology, Mangosuthu University of Technology, P.O. Box 12363, Durban 4026, South Africa.

The emergence of COVID-19 continues to pose severe threats to global public health. The pandemic has infected over 171 million people and claimed more than 3.5 million lives to date. Read More

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An overview of potential inhibitors targeting non-structural proteins 3 (PL and Mac1) and 5 (3CL/M) of SARS-CoV-2.

Comput Struct Biotechnol J 2021 24;19:4868-4883. Epub 2021 Aug 24.

Department of Physics, School of Science, Tianjin University, Tianjin 300072, China.

There is an urgent need to develop effective treatments for coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The rapid spread of SARS-CoV-2 has resulted in a global pandemic that has not only affected the daily lives of individuals but also had a significant impact on the global economy and public health. Although extensive research has been conducted to identify inhibitors targeting SARS-CoV-2, there are still no effective treatment strategies to combat COVID-19. Read More

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Co-crystallization and structure determination: An effective direction for anti-SARS-CoV-2 drug discovery.

Comput Struct Biotechnol J 2021 19;19:4684-4701. Epub 2021 Aug 19.

Key Laboratory of Green Natural Products and Pharmaceutical Intermediates in Colleges and Universities of Shandong Province, School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, PR China.

Safer and more-effective drugs are urgently needed to counter infections with the highly pathogenic SARS-CoV-2, cause of the COVID-19 pandemic. Identification of efficient inhibitors to treat and prevent SARS-CoV-2 infection is a predominant focus. Encouragingly, using X-ray crystal structures of therapeutically relevant drug targets (PL, M, RdRp, and S glycoprotein) offers a valuable direction for anti-SARS-CoV-2 drug discovery and lead optimization through direct visualization of interactions. Read More

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Evaluating Stability and Activity of SARS-CoV-2 PLpro for High-throughput Screening of Inhibitors.

Mol Biotechnol 2021 Aug 22. Epub 2021 Aug 22.

Protein Crystallography Section, Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, 400085, India.

Because of the essential roles of SARS-CoV-2 papain-like protease (PLpro) in the viral polyprotein processing and suppression of host immune responses, it is a crucial target for drug discovery against COVID-19. To develop robust biochemical methodologies for inhibitor screening against PLpro, extensive characterization of recombinant protein is important. Here we report cloning, expression, and purification of the recombinant SARS-CoV-2 PLpro, and explore various parameters affecting its stability and the catalytic activity. Read More

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Molecular modelling on SARS-CoV-2 papain-like protease: an integrated study with homology modelling, molecular docking, and molecular dynamics simulations.

SAR QSAR Environ Res 2021 Sep 16;32(9):699-718. Epub 2021 Aug 16.

Department of Biotechnology, Faculty of Biotechnology, Sumbawa University of Technology, Sumbawa, Indonesia.

SARS-CoV-2 PLpro was investigated as a therapeutic target for potent antiviral drugs due to its essential role in not only viral replication but also in regulating the inborn immune response. Several computational approaches, including homology modelling, molecular docking, and molecular dynamics (MD) studies, were employed to search for promising drugs in treating SARS-CoV-2. Eighty-one compounds, sub-structurally similar to the antiviral drug, were used as potential inhibitors of PLpro. Read More

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September 2021

The Promising Enzymes for Inhibitors Development against COVID-19.

Mini Rev Med Chem 2021 Aug 4. Epub 2021 Aug 4.

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, No.163 Xianlin Road, Nanjing 210023. China.

Since the outbreak of COVID-19, it has been an epidemic for nearly a year. COVID-19 has brought painful disasters to people all over the world. It not only threatens lives and health, but also induces economic crises. Read More

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Rilpivirine inhibits SARS-CoV-2 protein targets: A potential multi-target drug.

J Infect Public Health 2021 Jul 21. Epub 2021 Jul 21.

Texas Tech University Health Sciences Center, El Paso, TX, USA.

Background: COVID-19 disease caused by SARS-CoV-2 is lacking efficient medication although certain medications are used to relief its symptoms.

Objectives: We tested an FDA-approved antiviral medication namely rilpivirine to find a drug against SARS-CoV-2.

Methods: The inhibition of rilpivirine against multiple SARS-CoV-2 therapeutic targets was studied using in silico method. Read More

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Losartan Inhibits SARS-CoV-2 Replication in Vitro.

J Pharm Pharm Sci 2021 ;24:390-399

Alliance Retina Consultants, Inc.

Purpose: SARS-CoV-2 infection is associated with substantial mortality and high morbidity. This study tested the effect of angiotensin II type I receptor blocker, losartan, on SARS-CoV-2 replication and inhibition of the papain-like protease of the virus.

Methods: The dose-dependent inhibitory effect of losartan, in concentrations from 1μM to 100μM as determined by quantitative cell analysis combining fluorescence microscopy, image processing, and cellular measurements (Cellomics analysis) on SARS-CoV-2 replication was investigated in Vero E6 cells. Read More

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Biochemical characterization of protease activity of Nsp3 from SARS-CoV-2 and its inhibition by nanobodies.

PLoS One 2021 16;16(7):e0253364. Epub 2021 Jul 16.

MRC Protein Phosphorylation and Ubiquitylation Unit, Sir James Black Centre, School of Life Sciences, University of Dundee, Dundee, Scotland, United Kingdom.

Of the 16 non-structural proteins (Nsps) encoded by SARS CoV-2, Nsp3 is the largest and plays important roles in the viral life cycle. Being a large, multidomain, transmembrane protein, Nsp3 has been the most challenging Nsp to characterize. Encoded within Nsp3 is the papain-like protease domain (PLpro) that cleaves not only the viral polypeptide but also K48-linked polyubiquitin and the ubiquitin-like modifier, ISG15, from host cell proteins. Read More

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Multifunctional inhibitors of SARS-CoV-2 by MM/PBSA, essential dynamics, and molecular dynamic investigations.

J Mol Graph Model 2021 09 17;107:107969. Epub 2021 Jun 17.

Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, 247667, India. Electronic address:

The ongoing COVID-19 pandemic demands a novel approach to combat and identify potential therapeutic targets. The SARS-CoV-2 infection causes a hyperimmune response followed by a spectrum of diseases. Limonoids are a class of triterpenoids known to prevent the release of IL-6, IL-15, IL-1α, IL-1β via TNF and are also known to modulate PI3K/Akt/GSK-3β, JNK1/2, MAPKp38, ERK1/2, and PI3K/Akt/mTOR signaling pathways and could help to avoid viral infection, persistence, and pathogenesis. Read More

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September 2021

Mechanistic Aspects of Medicinal Plants and Secondary Metabolites against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

Curr Pharm Des 2021 Jul 5. Epub 2021 Jul 5.

Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Background And Objective: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a highly pathogenic virus, is responsible for a respiratory disease termed coronavirus disease 2019 (COVID-19). SARS-CoV-2 genome encodes various structural and non-structural proteins, which are necessary for viral entry and replication. Among these proteins, papain-like protease (PLpro), 3C-like protease (3CLpro), RNA-dependent RNA polymerase (RdRp), helicase, a serine protease, and spike protein are potential targets of herbal remedies and phytocompounds for inhibition of viral infection and replication. Read More

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Roles of existing drug and drug targets for COVID-19 management.

Metabol Open 2021 Sep 29;11:100103. Epub 2021 Jun 29.

Department of Pharmacology, School of Pharmacy, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia.

In December 2019, a highly transmissible, pneumonia epidemic caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), erupted in China and other countries, resulting in devastation and health crisis worldwide currently. The search and using existing drugs support to curb the current highly contagious viral infection is spirally increasing since the pandemic began. This is based on these drugs had against other related RNA-viruses such as MERS-Cov, and SARS-Cov. Read More

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September 2021

Antiviral Activity of Metabolites from Peruvian Plants against SARS-CoV-2: An In Silico Approach.

Molecules 2021 Jun 25;26(13). Epub 2021 Jun 25.

Vicerrectorado de Investigación, Universidad Católica de Santa María, Urb. San José s/n-Umacollo, Arequipa 04000, Peru.

(1) Background: The COVID-19 pandemic lacks treatments; for this reason, the search for potential compounds against therapeutic targets is still necessary. Bioinformatics tools have allowed the rapid in silico screening of possible new metabolite candidates from natural resources or repurposing known ones. Thus, in this work, we aimed to select phytochemical candidates from Peruvian plants with antiviral potential against three therapeutical targets of SARS-CoV-2. Read More

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Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of Nsp3 papain-like protease.

Biochem J 2021 07;478(13):2517-2531

Chromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.

The COVID-19 pandemic has emerged as the biggest life-threatening disease of this century. Whilst vaccination should provide a long-term solution, this is pitted against the constant threat of mutations in the virus rendering the current vaccines less effective. Consequently, small molecule antiviral agents would be extremely useful to complement the vaccination program. Read More

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screening of phytopolyphenolics for the identification of bioactive compounds as novel protease inhibitors effective against SARS-CoV-2.

J Biomol Struct Dyn 2021 Jun 28:1-17. Epub 2021 Jun 28.

R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India.

Due to the unavailability specific drugs or vaccines (FDA approved) that can cure COVID-19, the development of potent antiviral drug candidates/therapeutic molecules against COVID-19 is urgently required. This study was aimed at screening and study of polyphenolic phytochemical compounds in a rational way by virtual screening, molecular docking and molecular dynamics studies against SARS-CoV-2 main protease (Mpro) and papain-like protease (PLpro) enzymes. The objective of the study was to identify plant-derived polyphenolic compounds and/or flavonoid molecules as possible antiviral agents with protease inhibitory potential against SARS-CoV-2. Read More

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Phycobilins as Potent Food Bioactive Broad-Spectrum Inhibitors Against Proteases of SARS-CoV-2 and Other Coronaviruses: A Preliminary Study.

Front Microbiol 2021 10;12:645713. Epub 2021 Jun 10.

Meharry Medical College, Nashville, TN, United States.

In the 21st century, we have witnessed three coronavirus outbreaks: SARS in 2003, MERS in 2012, and the ongoing pandemic coronavirus disease 2019 (COVID-19). The search for efficient vaccines and development and repurposing of therapeutic drugs are the major approaches in the COVID-19 pandemic research area. There are concerns about the evolution of mutant strains (e. Read More

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Conformational Dynamics in the Interaction of SARS-CoV-2 Papain-like Protease with Human Interferon-Stimulated Gene 15 Protein.

J Phys Chem Lett 2021 Jun 10;12(23):5608-5615. Epub 2021 Jun 10.

Neutron Scattering Division, Oak Ridge National Laboratory, 1 Bethel Valley Road, Oak Ridge, Tennessee 37831, United States.

Papain-like protease (PLpro) from SARS-CoV-2 plays essential roles in the replication cycle of the virus. In particular, it preferentially interacts with and cleaves human interferon-stimulated gene 15 (hISG15) to suppress the innate immune response of the host. We used small-angle X-ray and neutron scattering combined with computational techniques to study the mechanism of interaction of SARS-CoV-2 PLpro with hISG15. Read More

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Computational prediction of nimbanal as potential antagonist of respiratory syndrome coronavirus.

Inform Med Unlocked 2021 28;24:100617. Epub 2021 May 28.

Department of Biochemistry, Faculty of Basic Medical Sciences, Ladoke Akintola University of Technology, Nigeria.

The high pathogenic nature of the Middle East Respiratory coronavirus (MER) and the associated high fatality rate demands an urgent attention from researchers. Because there is currently no approved drug for the management of the disease, research efforts have been intensified towards the discovery of a potent drug for the treatment of the disease. Papain Like protease (PLpro) is one of the key proteins involved in the viral replication. Read More

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Binding of SARS-CoV Covalent Non-Covalent Inhibitors to the SARS-CoV-2 Papain-Like Protease and Ovarian Tumor Domain Deubiquitinases.

Biomolecules 2021 05 28;11(6). Epub 2021 May 28.

Molecular Simulations and Design Group, Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstrasse 1, 39106 Magdeburg, Germany.

The urgent need for novel and effective drugs against the SARS-CoV-2 coronavirus pandemic has stimulated research worldwide. The Papain-like protease (PLpro), which is essential for viral replication, shares a similar active site structural architecture to other cysteine proteases. Here, we have used representatives of the Ovarian Tumor Domain deubiquitinase family OTUB1 and OTUB2 along with the PLpro of SARS-CoV-2 to validate and rationalize the binding of inhibitors from previous SARS-CoV candidate compounds. Read More

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Interplay of the ubiquitin proteasome system and the innate immune response is essential for the replication of infectious bronchitis virus.

Arch Virol 2021 Aug 26;166(8):2173-2185. Epub 2021 May 26.

Key Laboratory of Animal Virology of Ministry of Agriculture, Department of Veterinary Medicine, College of Animal Science, Zhejiang University, 866 Yuhangtang Road, Hangzhou, People's Republic of China.

Infectious bronchitis virus (IBV) is the only coronavirus known to infect poultry. The replication and pathogenesis of IBV are poorly understood, mainly because of the unavailability of a robust cell culture system. Here, we report that an active ubiquitin proteasome system (UPS) is necessary for efficient replication of IBV in Vero cells. Read More

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The SARS-CoV-2 SSHHPS Recognized by the Papain-like Protease.

ACS Infect Dis 2021 06 21;7(6):1483-1502. Epub 2021 May 21.

Center for Bio/molecular Science and Engineering (CBMSE), U.S. Naval Research Laboratory, 4555 Overlook Avenue, Washington, DC 20375, United States.

Viral proteases are highly specific and recognize conserved cleavage site sequences of ∼6-8 amino acids. Short stretches of homologous host-pathogen sequences (SSHHPS) can be found spanning the viral protease cleavage sites. We hypothesized that these sequences corresponded to specific host protein targets since >40 host proteins have been shown to be cleaved by Group IV viral proteases and one Group VI viral protease. Read More

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In silico Studies on the Interaction between Mpro and PLpro From SARS-CoV-2 and Ebselen, its Metabolites and Derivatives.

Mol Inform 2021 08 21;40(8):e2100028. Epub 2021 May 21.

Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria (UFSM), Santa Maria, 97105-900, RS, Brazil.

The COVID-19 pandemic caused by the SARS-CoV-2 has mobilized scientific attention in search of a treatment. The cysteine-proteases, main protease (Mpro) and papain-like protease (PLpro) are important targets for antiviral drugs. In this work, we simulate the interactions between the Mpro and PLpro with Ebselen, its metabolites and derivatives with the aim of finding molecules that can potentially inhibit these enzymes. Read More

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Unraveling the unbinding pathways of SARS-CoV-2 Papain-like proteinase known inhibitors by Supervised Molecular Dynamics simulation.

PLoS One 2021 19;16(5):e0251910. Epub 2021 May 19.

Department of Biology, Faculty of Science, Golestan University, Gorgan, Iran.

The COVID-19 disease has infected and killed countless people all over the world since its emergence at the end of 2019. No specific therapy for COVID-19 is not currently available, and urgent treatment solutions are needed. Recent studies have found several potential molecular targets, and one of the most critical proteins of the SARS-CoV-2 virus work machine is the Papain-like protease (Plpro). Read More

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Meticulous assessment of natural compounds from NPASS database for identifying analogue of GRL0617, the only known inhibitor for SARS-CoV2 papain-like protease (PLpro) using rigorous computational workflow.

Mol Divers 2021 May 18. Epub 2021 May 18.

Department of Microbiology & Biotechnology, University School of Sciences, Gujarat University, Ahmedabad, Gujarat, 380009, India.

The latest global outbreak of 2019 respiratory coronavirus disease (COVID-19) is triggered by the inception of novel coronavirus SARS-CoV2. If recent events are of any indicators of the epidemics of past, it is undeniable to state a fact that the SARS-CoV2 viral infection is highly transmissible with respect to its previously related SARS-CoV's. Papain-like protease (PLpro) is an enzyme that is required by the virus itself for replicating into the host system; and it does so by processing its polyproteins into a functional replicase complex. Read More

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Promising anti-SARS-CoV-2 drugs by effective dual targeting against the viral and host proteases.

Bioorg Med Chem Lett 2021 07 10;43:128099. Epub 2021 May 10.

Research Institute for Medical and Health Sciences, University of Sharjah, P.O. Box 27272, Sharjah, United Arab Emirates; College of Pharmacy, University of Sharjah, P.O. Box 27272, Sharjah, United Arab Emirates. Electronic address:

SARS-CoV-2 caused dramatic health, social and economic threats to the globe. With this threat, the expectation of future outbreak, and the shortage of anti-viral drugs, scientists were challenged to develop novel antivirals. The objective of this study is to develop novel anti-SARS-CoV-2 compounds with dual activity by targeting valuable less-mutated enzymes. Read More

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Reinforcing our defense or weakening the enemy? A comparative overview of defensive and offensive strategies developed to confront COVID-19.

Drug Metab Rev 2021 Jun 4:1-34. Epub 2021 Jun 4.

Department of Microbiology, Faculty of Basic Sciences, Lahijan Branch, Islamic Azad University (IAU), Lahijan, Guilan, Iran.

Developing effective strategies to confront coronavirus disease 2019 (COVID-19) has become one of the greatest concerns of the scientific community. In addition to the vast number of global mortalities due to COVID-19, since its outbreak, almost every aspect of human lives has changed one way or another. In the present review, various defensive and offensive strategies developed to confront COVID-19 are illustrated. Read More

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Development of potent and selective inhibitors targeting the papain-like protease of SARS-CoV-2.

Cell Chem Biol 2021 06 27;28(6):855-865.e9. Epub 2021 Apr 27.

Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China. Electronic address:

The COVID-19 pandemic has been disastrous to society and effective drugs are urgently needed. The papain-like protease domain (PLpro) of SARS-CoV-2 (SCoV2) is indispensable for viral replication and represents a putative target for pharmacological intervention. In this work, we describe the development of a potent and selective SCoV2 PLpro inhibitor, 19. Read More

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SARS-CoV-2 Papain-Like Protease Potential Inhibitors-In Silico Quantitative Assessment.

Int J Mol Sci 2021 Apr 12;22(8). Epub 2021 Apr 12.

Centre of New Technologies, University of Warsaw, Banacha 2c, 02-097 Warsaw, Poland.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes the papain-like protease (PLpro). The protein not only plays an essential role in viral replication but also cleaves ubiquitin and ubiquitin-like interferon-stimulated gene 15 protein (ISG15) from host proteins, making it an important target for developing new antiviral drugs. In this study, we searched for novel, noncovalent potential PLpro inhibitors by employing a multistep in silico screening of a 15 million compound library. Read More

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In search of RdRp and Mpro inhibitors against SARS CoV-2: Molecular docking, molecular dynamic simulations and ADMET analysis.

J Mol Struct 2021 Sep 21;1239:130488. Epub 2021 Apr 21.

L.M. College of Pharmacy, Navrangpura, Ahmedabad 380 009, Gujarat, India.

Corona Virus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome coronavirus (SARS CoV-2) has been declared a worldwide pandemic by WHO recently. The complete understanding of the complex genomic structure of SARS CoV-2 has enabled the use of computational tools in search of SARS CoV-2 inhibitors against the multiple proteins responsible for its entry and multiplication in human cells. With this endeavor, 177 natural, anti-viral chemical entities and their derivatives, selected through the critical analysis of the literatures, were studied using pharmacophore screening followed by molecular docking against RNA dependent RNA polymerase and main protease. Read More

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September 2021

Interactions between SARS coronavirus 2 papain-like protease and immune system: A potential drug target for the treatment of COVID-19.

Scand J Immunol 2021 Oct 10;94(4):e13044. Epub 2021 Aug 10.

Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Coronaviruses (CoVs) are a large family of respiratory viruses which can cause mild to moderate upper respiratory tract infections. Recently, new coronavirus named as Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified which is a major threat to public health. Innate immune responses play a vital role in a host's defence against viruses. Read More

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October 2021