Protease inhibitors as potential antiviral agents for the treatment of picornaviral infections

2001 ◽  
pp. 229-253 ◽  
Author(s):  
Q. May Wang
Keyword(s):  
Protease Inhibitors ◽  
Antiviral Agents

scholarly journals Protease Inhibitors as Antiviral Agents

1998 ◽  
Vol 11 (4) ◽  
pp. 614-627 ◽  
Author(s):  
A. K. Patick ◽  
K. E. Potts
Keyword(s):  
Protease Inhibitors ◽  
Viral Infections ◽  
Critical Role ◽  
Antiviral Agents ◽  
Antiviral Agent ◽  
Structural Proteins ◽  
Viral Protease ◽  
Virus Particles ◽  
Viral Proteases ◽  
Viral Polyprotein

SUMMARY Currently, there are a number of approved antiviral agents for use in the treatment of viral infections. However, many instances exist in which the use of a second antiviral agent would be beneficial because it would allow the option of either an alternative or a combination therapeutic approach. Accordingly, virus-encoded proteases have emerged as new targets for antiviral intervention. Molecular studies have indicated that viral proteases play a critical role in the life cycle of many viruses by effecting the cleavage of high-molecular-weight viral polyprotein precursors to yield functional products or by catalyzing the processing of the structural proteins necessary for assembly and morphogenesis of virus particles. This review summarizes some of the important general features of virus-encoded proteases and highlights new advances and/or specific challenges that are associated with the research and development of viral protease inhibitors. Specifically, the viral proteases encoded by the herpesvirus, retrovirus, hepatitis C virus, and human rhinovirus families are discussed.

scholarly journals Computer-aided identification of a series of novel ligands showing high potency as hepatitis C virus NS3/4A protease inhibitors

2021 ◽  
Vol 45 (1) ◽  
Author(s):  
Stephen Ejeh ◽  
Adamu Uzairu ◽  
Gideon Adamu Shallangwa ◽  
Stephen E. Abechi
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Binding Energy ◽  
Protease Inhibitor ◽  
Protease Inhibitors ◽  
Antiviral Agents ◽  
High Potency ◽  
Direct Acting Antiviral ◽  
Direct Acting ◽  
Direct Acting Antiviral Agents

Abstract Background Hepatitis C virus (HCV) is a global medical condition that causes several life-threatening chronic diseases in the liver. The conventional interferon-free treatment regimens are currently in use by a blend of direct-acting antiviral agents (DAAs) aiming at the viral NS3 protease. However, major concerns may be the issue of DAA-resistant HCV strains and the limited availability to the DAAs due to their high price. Due to this crisis, the developments of a new molecule with high potency as an NS3/4A protease inhibitor of the hepatitis-C virus remain a high priority for medical research. This study aimed to use in-silico methods to identify high potent molecule as an NS3/4A protease inhibitor and investigating the binding energy of the identified molecule in comparison with approved direct-acting antiviral agents (Telaprevir, Simeprevir, and Voxilaprevir) through molecular docking. Results The model obtained by in-silico method have the following statistical records, coefficient of determination (r2) of 0.7704, cross-validation (q2LOO = 0.6914); external test set (r2(pred) = 0.7049) and Y-randomization assessment (cR2p = 0.7025). The results from the model were used to identify 12 new potential human HCV NS3/4A protease inhibitors, and it was observed that the identified molecule is well-fixed when docked with the receptor and was found to have the lowest binding energy of − 10.7, compared to approved direct-acting antiviral agents (Telaprevir, Simeprevir, and Voxilaprevir) with − 9.5, − 10.0, − 10.5 binding energy, respectively. Conclusion The binding affinity (− 10.7) of the newly identified molecule docked with 3D structures of HCV NS3/4a protease/helicase (PDB ID: 4A92) was found to be better than that of Telaprevir, Simeprevir, and Voxilaprevir (approved direct-acting antiviral agents) which are − 9.5, − 10.0, and − 10.5, respectively. Hence, a novel molecule was identified showing high potency as HCV NS3/4a protease inhibitors.

Alphavirus capsid protease inhibitors as potential antiviral agents for Chikungunya infection

2020 ◽  
Vol 179 ◽  
pp. 104808 ◽  
Author(s):  
Benazir Fatma ◽  
Ravi Kumar ◽  
Vedita Anand Singh ◽  
Sanketkumar Nehul ◽  
Rajesh Sharma ◽  
...  
Keyword(s):  
Protease Inhibitors ◽  
Antiviral Agents

Successful treatment of resistant HCV in a patient with Child-Pugh B cirrhosis using sofosbuvir and glecaprevir/pibrentasvir

2020 ◽  
Vol 13 (7) ◽  
pp. e232931
Author(s):  
Munim Islam ◽  
Sarah Nicholas ◽  
Rhys Oakley ◽  
Brendan Healy
Keyword(s):  
Liver Transplantation ◽  
Protease Inhibitors ◽  
Successful Treatment ◽  
Treatment Options ◽  
Antiviral Agents ◽  
Effective Treatment Option ◽  
Direct Acting Antiviral ◽  
Almost All ◽  
Direct Acting ◽  
Direct Acting Antiviral Agents

Treatments for hepatitis C are now well tolerated with very high rates of sustained virological response and almost all patients have a suitable and effective treatment option. However, treatment options remain limited for a minority of patients and are limited for patients with Child-Pugh B or C cirrhosis due to the risk of decompensation with protease inhibitors. We present a case of successful treatment with glecaprevir/pibrentasvir (Maviret) and sofosbuvir in a patient with Child-Pugh B cirrhosis and resistant virus who had failed three previous attempts of treatment including two courses of direct acting antiviral agents and in whom liver transplantation was deemed unsuitable. We propose that the balance of risks favours a trial of treatment with protease inhibitors in some circumstances in patients with Child-Pugh B cirrhosis where no other suitable alternatives including treatment post liver transplantation are available/appropriate.

scholarly journals Antiviral Drug Discovery: Norovirus Proteases and Development of Inhibitors

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 197 ◽  
Author(s):  
Kyeong-Ok Chang ◽  
Yunjeong Kim ◽  
Scott Lovell ◽  
Athri Rathnayake ◽  
William Groutas
Keyword(s):  
Protease Inhibitors ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
Cysteine Proteases ◽  
Life Forms ◽  
Biological Processes ◽  
Macrocyclic Compounds ◽  
Viral Proteases ◽  
Wide Range ◽  
Immunodeficiency Virus

Proteases are a major enzyme group playing important roles in a wide variety of biological processes in life forms ranging from viruses to mammalians. The aberrant activity of proteases can lead to various diseases; consequently, host proteases have been the focus of intense investigation as potential therapeutic targets. A wide range of viruses encode proteases which play an essential role in viral replication and, therefore, constitute attractive targets for the development of antiviral therapeutics. There are numerous examples of successful drug development targeting cellular and viral proteases, including antivirals against human immunodeficiency virus and hepatitis C virus. Most FDA-approved antiviral agents are peptidomimetics and macrocyclic compounds that interact with the active site of a targeted protease. Norovirus proteases are cysteine proteases that contain a chymotrypsin-like fold in their 3D structures. This review focuses on our group’s efforts related to the development of norovirus protease inhibitors as potential anti-norovirus therapeutics. These protease inhibitors are rationally designed transition-state inhibitors encompassing dipeptidyl, tripeptidyl and macrocyclic compounds. Highly effective inhibitors validated in X-ray co-crystallization, enzyme and cell-based assays, as well as an animal model, were generated by launching an optimization campaign utilizing the initial hit compounds. A prodrug approach was also explored to improve the pharmacokinetics (PK) of the identified inhibitors.

Antiviral agents against COVID-19: structure-based design of specific peptidomimetic inhibitors of SARS-CoV-2 main protease

RSC Advances ◽  
2020 ◽  
Vol 10 (66) ◽  
pp. 40244-40263
Author(s):  
Vladimir Frecer ◽  
Stanislav Miertus
Keyword(s):  
Protease Inhibitors ◽  
Antiviral Agents ◽  
Main Protease ◽  
Peptidomimetic Inhibitors

Structure-based design of SARS-CoV-2 main protease inhibitors identified hydantoin, benzothiazine and cresol moieties as promising residues of new peptidomimetic inhibitors.

scholarly journals Time to Hit Opioids Early and Hard

2019 ◽  
Vol 2 (1) ◽  
pp. 01-02
Author(s):  
Ronald Moss
Keyword(s):  
Chronic Disease ◽  
Protease Inhibitors ◽  
Paradigm Shift ◽  
Turning Point ◽  
Antiviral Agents ◽  
Lessons Learned ◽  
Opioid Epidemic ◽  
Hiv Epidemic

A turning point in the HIV epidemic was the introduction of protease inhibitors. It was clear to some that treatment of HIV infected individuals with these potent antiviral agents was needed as early as possible, and with this paradigm shift, HIV became a livable chronic disease (1). There are some lessons learned from the HIV epidemic relevant to the current synthetic opioid epidemic.

Protease Inhibitors of the Sulfonamide Type: Anticancer, Antiinflammatory, and Antiviral Agents

ChemInform ◽  
2003 ◽  
Vol 34 (48) ◽  
Author(s):  
Claudiu T. Supuran ◽  
Angela Casini ◽  
Andrea Scozzafava
Keyword(s):  
Protease Inhibitors ◽  
Antiviral Agents

Evaluation of the Binding Affinity of Anti-Viral Drugs against Main Protease of SARS-CoV-2 through a Molecular Docking Study

2020 ◽  
Vol 20 ◽  
Author(s):  
Milon Mondal ◽  
Chandan Sarkar ◽  
Sarmin Jamaddar ◽  
Abul Bashar Ripon Khalipha ◽  
Muhammad Torequl Islam ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Protease Inhibitors ◽  
Binding Affinity ◽  
Rna Virus ◽  
Antiviral Treatment ◽  
Antiviral Agents ◽  
Docking Study ◽  
Multiple Organ ◽  
Molecular Docking Study ◽  
Viral Protease

Background: Coronavirus disease 2019 (COVID-19) is a life intimidating viral infection caused by a positive sense RNA virus belonging to the Coronaviridae family, named severe acute respiratory distress syndrome coronavirus 2 (SARA-CoV-2). Since its outbreak in December 2019, the pandemic has spread to more than 200 countries, infected more than 26 million, and claimed the lives of more than 800,000 people. As a disease, COVID-19 can lead to severe and occasionally fatal respiratory problems in humans. Infection with this virus is associated with fever, cough, dyspnea, and muscle aches, and it may progress to pneumonia, multiple organ failure, and death. To date, there is no specific antiviral treatment against this virus. However, the main viral protease has been recently discovered and it is regarded as an appropriate target for antiviral agents in the search for treatment of COVID-19, due to its pivotal role in polyproteins processing during viral replication. Aim: Consequently, this study intends to evaluate the effectiveness of FDA-approved anti-viral drugs against SARA-CoV-2 through a molecular docking study. Methods: AutoDock Vina in PyRx platform was used for docking analysis against the main viral protease (Mpro) (PDB ID 6LU7), and Computed Atlas of Surface Topography of proteins (CASTp 3.0) was applied for detecting and characterizing cavities, pockets, and channels of this protein structure. Results: Results revealed that among the conventional antiviral drugs, the protease inhibitors, lopinavir, amprenavir, indinavir, maraviroc, saquinavir, and daclatasvir showed high binding affinity and interacted with amino acid residues of the binding site. Conclusion: In conclusion, protease inhibitors may be effective potential antiviral agents against Mpro to combat SARSCoV-2.

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