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 Antiviral Agents for the Prevention and Treatment of Herpes Simplex Virus Type-1 Infection in Clinical Oncology: A Network Meta-Analysis

2020 ◽  
Vol 17 (23) ◽  
pp. 8891
Author(s):  
Farah Wasim Aribi Al-Zoobaee ◽  
Loo Yee Shen ◽  
Sajesh K. Veettil ◽  
Divya Gopinath ◽  
Mari Kannan Maharajan ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Viral Infections ◽  
Meta Analysis ◽  
Antiviral Agents ◽  
Antiviral Agent ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Assessment Development ◽  
Simplex Virus

Cancer therapy may be complicated and compromised by viral infections, including oral herpes simplex virus (HSV) infection. This network meta-analysis aimed to identify the best antiviral agent to prevent or treat oral HSV infection in patients being treated for cancer. A search was conducted for trials published since inception until the 10th of May 2020 in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. A network meta-analysis was performed on the data from randomized controlled trials that assessed antiviral agents for preventive or therapeutic activity vs. placebo, no treatment or any other active intervention in patients being treated for cancer. The agents were ranked according to their effectiveness in the prevention of oral HSV using surface under the cumulative ranking (SUCRA). Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to assess the certainty of the evidence. In total, 16 articles were included. The pooled relative risk (RR) to develop oral HSV infection in the acyclovir group was 0.17 (95% CI: 0.10, 0.30), compared to 0.22 (95% CI: 0.06, 0.77) in the valacyclovir group. Acyclovir ranked highest for the prevention of oral HSV followed by valacyclovir. Subgroup analysis with different acyclovir regimens revealed that the best regimens in terms of HSV-1 prevention were 750 mg/m2 acyclovir administered intravenously followed by 1600 mg per day orally. Acyclovir (250 mg/m2 per day) administered intravenously was the least effective against the prevention of oral HSV.

scholarly journals Has Ivermectin Virus-Directed Effects against SARS-CoV-2? Rationalizing the Action of a Potential Multitarget Antiviral Agent

2020 ◽  
Author(s):  
Antonio Francés-Monerris ◽  
Cristina Garcia-Iriepa ◽  
Isabel Iriepa ◽  
Cecilia Hognon ◽  
Tom Miclot ◽  
...  
Keyword(s):  
Wide Spectrum ◽  
Antiviral Agents ◽  
Antiviral Agent ◽  
Host Immune System ◽  
Structural Protein ◽  
Cell Infection ◽  
Viral Proteases ◽  
Potent Inhibition ◽  
Dynamics Simulations

The novel SARS-CoV-2 coronavirus is causing a devastating pandemic in 2020, threatening public health in many countries. An unprecedented rapid and global response has been set in motion to identify efficient antiviral agents against SARS-CoV-2, mostly relying on the repurposing of drugs presenting or not previously known antiviral activity. Ivermectin is an approved drug used as antiparasitic in humans and animals with well documented broad-spectrum antiviral properties that emerge from host-directed effects. Recent results reported by Wagstaff and coworkers (Antiviral Research <b>2020</b>, <i>178</i>, 104787) show a potent inhibition of SARS-CoV-2 replication <i>in vitro </i>by ivermectin, and clinical trials with human volunteers have already started. However, the mode of action of ivermectin is still largely unknown, especially at the molecular level. Here, we employ advanced molecular dynamics simulations to assess the influence of ivermectin on several key viral protein targets, with the aim to reveal the molecular bases of antiviral mechanisms against SARS-CoV-2. Interestingly, we show that ivermectin could be regarded as a multitarget agent, inhibiting different viral functions. These include blocking the recognition by the SARS-CoV-2 Receptor Binding Domain (RBD) of the Angiotensin-Converting Enzyme 2 (ACE2), the interactions with the two viral proteases 3CL<sup>pro</sup> and PL<sup>pro</sup>, and the SARS Unique Domain (SUD) non-structural protein. Hence, the wide spectrum of actions involving i) the interference with cell infection, ii) the inhibition of viral replication, and iii) elusion of the host immune system, could point to an unprecedented synergy between host- and virus-directed effects explaining the high anti-SARS-CoV-2 activity observed for this compound.

scholarly journals Natural products as anti-COVID-19 agents: An in silico study

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Chandan Sarkar ◽  
Sarmin Jamaddar ◽  
Milon Mondal ◽  
Abul Bashar Ripon Khalipha ◽  
Muhammad Torequl Islam ◽  
...  
Keyword(s):  
In Silico ◽  
Rna Virus ◽  
Antiviral Agents ◽  
Antiviral Agent ◽  
Docking Study ◽  
Asiatic Acid ◽  
Molecular Docking Study ◽  
Viral Protease ◽  
In Silico Study ◽  
To Come

Background: The coronavirus disease 2019 (COVID-19) is a life threatening viral infection caused by a positivestrand RNA virus belonging to Coronaviridae family called severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2). This virus has infected millions of peoples, and caused hundreds of thousands of deaths around the world. Unfortunately, to date, there is no specific cure for SARS-CoV-2 infection, although researchers are working tirelessly to come up with a drug against this virus. Recently, the main viral protease has been discovered, and is regarded as an appropriate target for antiviral agents in the search for treatment of SARS-CoV-2 infection, due to its role in polyproteins processing during coronavirus replication. Methodology: This investigation (an in silico study) explores the effectiveness of 16 natural compounds from a literature survey against the protease of SARS-CoV-2 in an attempt to identify a promising antiviral agent through a molecular docking study. Results: Among the 16 compounds studied, apigenin, alpha-hederin, and asiatic acid exhibited significant docking performance and interacted with several amino acid residues of the main protease of SARS-CoV-2. Conclusion: In summary, apigenin, alpha-hederin, and asiatic acid protease inhibitors may be effective potential antiviral agents against the main viral protease (Mpro) to combat SARS-CoV-2.

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.

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.

Zinc Oxide Nanoparticles as a Potential Agent for Antiviral Drug Delivery Development; A Systematic Literature Review

2021 ◽  
Vol 17 ◽  
Author(s):  
Mahda sadat Nasrollahzadeh ◽  
Razieh Ghodsi ◽  
Farzin Hadizadeh ◽  
Mahdi Faal Maleki ◽  
Mohammad Mashreghi ◽  
...  
Keyword(s):  
Zinc Oxide ◽  
Metal Oxide ◽  
Viral Infections ◽  
Relevant Literature ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
Antiviral Agent ◽  
Human Studies ◽  
Inclusion Criteria ◽  
Zno Nps

: Viral infection is a worldwide health problem, which has negatively affected global activity in recent years. There is no specific medication for most viral infections, and the treatments are based on symptom management. Nanoparticles (NPs) in recent years have shown promising antibacterial and antiviral properties, among which metal oxide NPs have shown superiority. In the present study, we aimed to systematically review all available literature supporting the efficiency of zinc oxide (ZnO) NPs in the treatment of viral infections. For this purpose, a systematic literature search was performed in scientific literature databases including PubMed, Scopus, Web of Science, Science Direct, Ovid, Embase, and Google Scholar by using “viral infections”, “antiviral effects,” and “ZnO NPs” in addition to all their equivalent terms as keywords. Due to the lack of human studies, no strict inclusion criteria were defined, and all available relevant literature were included. A total of 14 documents that fully met the inclusion criteria were retrieved and used for data synthesis. The results showed that ZnO NPs, due to some specific physiochemical properties, can be a promising approach in developing antiviral agents and nanovaccines, especially against RNA viruses, such as human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus. The most probable antiviral mechanistic pathways of ZnO NPs were blocking the virus entry into the cells and deactivation of the virus through virostatic potential. Based on the findings of the included studies, it is suggested that ZnO NPs and other metal oxide-based NPs may be a potential antiviral agent; however, further human studies are required to confirm such efficiency in clinical practice.

scholarly journals Has Ivermectin Virus-Directed Effects against SARS-CoV-2? Rationalizing the Action of a Potential Multitarget Antiviral Agent

2020 ◽  
Author(s):  
Antonio Francés-Monerris ◽  
Cristina Garcia-Iriepa ◽  
Isabel Iriepa ◽  
Cecilia Hognon ◽  
Tom Miclot ◽  
...  
Keyword(s):  
Wide Spectrum ◽  
Antiviral Agents ◽  
Antiviral Agent ◽  
Host Immune System ◽  
Structural Protein ◽  
Cell Infection ◽  
Viral Proteases ◽  
Potent Inhibition ◽  
Dynamics Simulations

The novel SARS-CoV-2 coronavirus is causing a devastating pandemic in 2020, threatening public health in many countries. An unprecedented rapid and global response has been set in motion to identify efficient antiviral agents against SARS-CoV-2, mostly relying on the repurposing of drugs presenting or not previously known antiviral activity. Ivermectin is an approved drug used as antiparasitic in humans and animals with well documented broad-spectrum antiviral properties that emerge from host-directed effects. Recent results reported by Wagstaff and coworkers (Antiviral Research <b>2020</b>, <i>178</i>, 104787) show a potent inhibition of SARS-CoV-2 replication <i>in vitro </i>by ivermectin, and clinical trials with human volunteers have already started. However, the mode of action of ivermectin is still largely unknown, especially at the molecular level. Here, we employ advanced molecular dynamics simulations to assess the influence of ivermectin on several key viral protein targets, with the aim to reveal the molecular bases of antiviral mechanisms against SARS-CoV-2. Interestingly, we show that ivermectin could be regarded as a multitarget agent, inhibiting different viral functions. These include blocking the recognition by the SARS-CoV-2 Receptor Binding Domain (RBD) of the Angiotensin-Converting Enzyme 2 (ACE2), the interactions with the two viral proteases 3CL<sup>pro</sup> and PL<sup>pro</sup>, and the SARS Unique Domain (SUD) non-structural protein. Hence, the wide spectrum of actions involving i) the interference with cell infection, ii) the inhibition of viral replication, and iii) elusion of the host immune system, could point to an unprecedented synergy between host- and virus-directed effects explaining the high anti-SARS-CoV-2 activity observed for this compound.

Exposure of protein VP7 on the surface of bluetongue virus

1990 ◽  
Vol 48 (3) ◽  
pp. 600-601
Author(s):  
A.D. Hyatt
Keyword(s):  
Bluetongue Virus ◽  
Structural Proteins ◽  
Major Constituent ◽  
Outer Coat ◽  
Virus Particles ◽  
Antibody Recognition ◽  
The Core ◽  
The Family ◽  
Electron Microscopical ◽  
Physical Accessibility

Bluetongue virus (BTV) is the type species os the genus orbivirus in the family Reoviridae. The virus has a fibrillar outer coat containing two major structural proteins VP2 and VP5 which surround an icosahedral core. The core contains two major proteins VP3 and VP7 and three minor proteins VP1, VP4 and VP6. Recent evidence has indicated that the core comprises a neucleoprotein center which is surrounded by two protein layers; VP7, a major constituent of capsomeres comprises the outer and VP3 the inner layer of the core . Antibodies to VP7 are currently used in enzyme-linked immunosorbant assays and immuno-electron microscopical (JEM) tests for the detection of BTV. The tests involve the antibody recognition of VP7 on virus particles. In an attempt to understand how complete viruses can interact with antibodies to VP7 various antibody types and methodologies were utilized to determine the physical accessibility of the core to the external environment.

scholarly journals A possible interaction between favipiravir and methotrexate: Drug-induced hepatotoxicity in a patient with osteosarcoma

2021 ◽  
pp. 107815522110313
Author(s):  
Emre Demir ◽  
Osman Sütcüoğlu ◽  
Beril Demir ◽  
Oktay Ünsal ◽  
Ozan Yazıcı
Keyword(s):  
Drug Interactions ◽  
Toxic Hepatitis ◽  
Antiviral Agents ◽  
Antiviral Agent ◽  
Aldehyde Oxidase ◽  
Chemotherapeutic Agents ◽  
High Dose ◽  
Drug Induced ◽  
Metastatic Osteosarcoma ◽  
Grade 3

Introduction Favipiravir is an antiviral agent that is recently used for SARS-CoV2 infection. The drug-drug interactions of favipiravir especially with chemotherapeutic agents in a patient with malignancy are not well known. Case report The patient diagnosed with metastatic osteosarcoma was given high dose methotrexate treatment, and favipiravir was started on the third day of the treatment with suspicion of SARS-CoV2 infection. Grade 3 hepatotoxicity developed after favipiravir. Management & outcome: The acute viral hepatitis panel and autoimmune liver disease panel were negative. The ultrasound of the abdomen was unremarkable for any hepatobiliary pathology. The all viral and hepatobiliary possible etiological factors were ruled out. The patient’s liver enzymes increased just after (12 hours later) the initiation of favipiravir, and we diagnosed toxic hepatitis caused by favipiravir-methotrexate interaction. Therefore, methylprednisolone 1 mg/kg dose was started for a presumed diagnosis of toxic hepatitis. Hepatotoxicity completely regressed after favipiravir was discontinued. Discussion Favipiravir may inhibit methotrexate elimination by inhibiting aldehyde oxidase and its sequential use may cause hepatotoxicity in this case. The clinicians should keep in mind possible drug interactions while using new antiviral agents against SARS-CoV2 like favipiravir.

scholarly journals Nanobiocide Based-Silver Nanomaterials Upon Coronaviruses: Approaches for Preventing Viral Infections

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Kamyar Khoshnevisan ◽  
Hassan Maleki ◽  
Hadi Baharifar
Keyword(s):  
Viral Entry ◽  
Viral Infections ◽  
Respiratory Infections ◽  
Antiviral Agents ◽  
Long Term Stability ◽  
Silver Nanomaterials ◽  
Inhibitory Mechanisms ◽  
Low Toxicity ◽  
Nano Graphene

Abstract The effectiveness of silver nanomaterials (AgNMs), as antiviral agents, has been confirmed in humans against many different types of viruses. Nanobiocides-based AgNMs can be effectively applied to eliminate coronaviruses (CoVs), as the cause of various diseases in animals and humans, particularly the fatal human respiratory infections. Mostly, these NMs act effectively against CoVs, thanks to the NMs’ fundamental anti-viral structures like reactive oxygen species (ROS), and photo-dynamic and photo-thermal abilities. Particularly, the antiviral activity of AgNMs is clarified under three inhibitory mechanisms including viral entry limitation, attachment inhibition, and viral replication limitation. It is believed that nanobiocide with other possible materials such as TiO2, silica and, carbon NMs exclusively nano-graphene materials can emerge as a more effective disinfectant for long-term stability with low toxicity than common disinfectants. Nanobiocides also can be applied for the prevention and treatment of viral infections specifically against COVID-19. Graphic Abstract

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