-
Cold Spring Harbor Perspectives in... Aug 2019Novel hepeviruses have been recovered from many different animal species in recent years, increasing the diversity known to exist among the , which now include two... (Review)
Review
Novel hepeviruses have been recovered from many different animal species in recent years, increasing the diversity known to exist among the , which now include two genera, and Multiple viral genotypes in the species are able to replicate and cause acute hepatitis E in humans, and thus represent an important public health problem in industrialized as well as developing countries. Although hepatitis E virus (HEV) infections typically result in acute and self-limited hepatitis, immunocompromised and transplant patients are vulnerable to prolonged infections and to chronic hepatitis. Cell culture systems have been established for several HEV strains and offer new opportunities for the study of HEV biology. Similarly, a variety of new small animal models have been developed, using either nonhuman hepeviruses in their cognate hosts as surrogates for human HEV, or human HEV infection of immunodeficient mice with chimeric livers engrafted with human hepatocytes. These new models provide several advantages over previous nonhuman primate models of hepatitis E infection and will facilitate studies of pathogenicity, cross-species infection, mechanisms of virus replication, and vaccine and antiviral agent development. This article reviews the current understanding of small animal models for HEV.
Topics: Animals; Antiviral Agents; Chickens; Disease Models, Animal; Ferrets; Gerbillinae; Hepatitis E; Hepatitis E virus; Mice; Rabbits; Rats; Tupaiidae; Viral Hepatitis Vaccines
PubMed: 29735581
DOI: 10.1101/cshperspect.a032581 -
Drug Design, Development and Therapy 2022The aim of this report is to review the literature and shed light on the uncertainties surrounding the use of antiviral agents in general and remdesivir in COVID-19... (Review)
Review
The aim of this report is to review the literature and shed light on the uncertainties surrounding the use of antiviral agents in general and remdesivir in COVID-19 patients. This review evaluated a battery of antiviral compounds and their effectiveness in the treatment of COVID-19 since the beginning of the pandemic. Remdesivir is the only antiviral approved by the EMA and FDA for the treatment of SARS-CoV-2 infection. This work extensively reviews remdesivir data generated from clinical trials and observational studies, paying attention to the most recent data, and focusing on outcomes to give readers a more comprehensive understanding of the results. This review also discusses the recommendations issued by official bodies during the pandemic in the light of the current knowledge. The use of remdesivir in the treatment of SARS-CoV-2 infection is justified because a virus is the causative agent that triggers the inflammatory responses and its consequences. More trials are needed to improve the management of this disease.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Humans; SARS-CoV-2; Virus Replication; COVID-19 Drug Treatment
PubMed: 35370401
DOI: 10.2147/DDDT.S356951 -
Food and Environmental Virology Jun 2022The use of natural resources for the prevention and treatment of diseases considered fatal to humanity has evolved. Several medicinal plants have nutritional and... (Review)
Review
The use of natural resources for the prevention and treatment of diseases considered fatal to humanity has evolved. Several medicinal plants have nutritional and pharmacological potential in the prevention and treatment of viral infections, among them, turmeric, which is recognized for its biological properties associated with curcuminoids, mainly represented by curcumin, and found mostly in rhizomes. The purpose of this review was to compile the pharmacological activities of curcumin and its analogs, aiming at stimulating their use as a therapeutic strategy to treat infections caused by RNA genome viruses. We revisited its historical application as an anti-inflammatory, antioxidant, and antiviral agent that combined with low toxicity, motivated research against viruses affecting the population for decades. Most findings concentrate particularly on arboviruses, HIV, and the recent SARS-CoV-2. As one of the main conclusions, associating curcuminoids with nanomaterials increases solubility, bioavailability, and antiviral effects, characterized by blocking the entry of the virus into the cell or by inhibiting key enzymes in viral replication and transcription.
Topics: Antiviral Agents; Curcumin; Diarylheptanoids; Humans; RNA; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35352306
DOI: 10.1007/s12560-022-09514-3 -
Molecules (Basel, Switzerland) Mar 2023Pesticides are essential for the development of agriculture. It is urgent to develop green, safe and efficient pesticides. Bisindole alkaloids have unique and concise...
Pesticides are essential for the development of agriculture. It is urgent to develop green, safe and efficient pesticides. Bisindole alkaloids have unique and concise structures and broad biological activities, which make them an important leading skeleton in the creation of new pesticides. In this work, we synthesized bisindole alkaloid barakacin in a simple seven-step process, and simultaneously designed and synthesized a series of its derivatives. Biological activity research indicated that most of these compounds displayed good antiviral activities against tobacco mosaic virus (TMV). Among them, compound exerted a superior inhibitory effect in comparison to commercially available antiviral agent ribavirin, and could be expected to become a novel antiviral candidate. Molecular biology experiments and molecular docking research found that the potential target of compound was TMV coat protein (CP). These compounds also showed broad-spectrum anti-fungal activities against seven kinds of plant fungi.
Topics: Antiviral Agents; Structure-Activity Relationship; Molecular Docking Simulation; Fungicides, Industrial; Ribavirin; Tobacco Mosaic Virus; Alkaloids; Drug Design
PubMed: 37049795
DOI: 10.3390/molecules28073032 -
Cytometry. Part B, Clinical Cytometry Jan 2021With the morbidity and mortality associated with the COVID-19 pandemic that we are witnessing this year, the risks posed by emerging viral diseases to global health are... (Review)
Review
With the morbidity and mortality associated with the COVID-19 pandemic that we are witnessing this year, the risks posed by emerging viral diseases to global health are all too obvious. This pandemic highlights the importance of antiviral drug discovery, which targets emerging viral pathogens, as well as existing pathogenic viruses that undergo continuous evolution. Drug discovery and development is a long and resource intensive process; however, the use of biomarkers can accelerate clinical development of antivirals by providing information regarding diagnosis of specific viral infections, status of infection, potential safety parameters, and antiviral responses. In clinical practice, many of the biomarkers initially utilized to support clinical development are also used for patient care. While viral load is a standard and essential biomarker used to detect the desired viral suppression induced by an antiviral agent, it has become apparent that additional biomarkers, whether related to the virus, the host or as a consequence of the drug's mechanistic effects, are also important for monitoring clinical outcomes associated with an antiviral therapy. This review summarizes the biomarkers used in the clinical development (as well as in clinical practice, where appropriate) of antiviral therapies for hepatitis C virus, hepatitis B virus, human immunodeficiency virus, and severe acute respiratory syndrome coronavirus 2.
Topics: Animals; Antiviral Agents; Biomarkers; COVID-19; Clinical Trials as Topic; Humans; SARS-CoV-2; Virus Diseases; COVID-19 Drug Treatment
PubMed: 34542933
DOI: 10.1002/cyto.b.21974 -
Molecules (Basel, Switzerland) Oct 2022A series of oxazinyl flavonoids were synthesized on the basis of flavone. The structures of all target compounds were characterized by H NMR, C NMR, and HRMS. The effect...
A series of oxazinyl flavonoids were synthesized on the basis of flavone. The structures of all target compounds were characterized by H NMR, C NMR, and HRMS. The effect of the different substituent on the N-position of oxazinyl flavonoids against tobacco mosaic virus (TMV) activities and plant pathogen activities was systematically investigated. In vivo anti-TMV activity showed that most of the compounds showed moderate-to-excellent antiviral activities against TMV at 500 μg/mL. Compounds , , -, and - showed better antiviral activities than ribavirin (a commercially available antiviral agent) and apigenin. In particular, compounds and even displayed slightly higher activities than ningnanmycin, which were expected to become new antiviral candidates. Antiviral mechanism research by molecular docking exhibited that compounds and could interact with TMV CP and inhibit virus assembly. Then, the antifungal activities of these compounds against six kinds of plant pathogenic fungi were tested, and the results showed that these oxazinyl flavonoids had broad-spectrum fungicidal activities. Compounds exhibited antifungal activity of up to 91% against and might become a candidate drug for new fungicides.
Topics: Antiviral Agents; Ribavirin; Fungicides, Industrial; Antifungal Agents; Structure-Activity Relationship; Flavonoids; Molecular Docking Simulation; Apigenin; Molecular Structure; Alkaloids; Tobacco Mosaic Virus; Fungi; Drug Design
PubMed: 36296469
DOI: 10.3390/molecules27206875 -
Future Medicinal Chemistry May 2022In the last two decades, the world has witnessed the emergence of zoonotic corona viruses (CoVs), which cause mild to severe respiratory diseases in humans. Human...
In the last two decades, the world has witnessed the emergence of zoonotic corona viruses (CoVs), which cause mild to severe respiratory diseases in humans. Human coronaviruses (HCoVs), mainly from the alpha-CoV and beta-CoV genera, have evolved to be highly pathogenic, such as SARS-CoV-2 causing the COVID-19 pandemic. These coronaviruses carry functional enzymes necessary for the virus life cycle, which represent attractive antiviral targets. We aimed to therapeutically target the main protease (Mpro) of HCoV-NL63 and HCoV-229E (from alpha-CoV genus) and HCoV-OC43 and SARS-CoV-2 (from beta-CoV genus). Through virtual screening, we identified an FDA-approved drug dyphylline, a xanthine derivate, that binds to the catalytic dyad residues; histidine and cystine of the Mpro structures. Importantly, dyphylline dose-dependently inhibited the viral replication in cell culture models infected with the viruses. Our findings support the repurposing of dyphylline as a pan-coronavirus antiviral agent.
Topics: Antiviral Agents; Drug Repositioning; Dyphylline; Humans; Pandemics; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35387498
DOI: 10.4155/fmc-2021-0311 -
The Journal of Antimicrobial... Oct 2022Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the aetiological agent of coronavirus disease 2019 (COVID-19) and a devastating worldwide health concern....
OBJECTIVES
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the aetiological agent of coronavirus disease 2019 (COVID-19) and a devastating worldwide health concern. Development of safe and effective treatments is not only important for interventions during the current pandemic, but also for providing general treatment options moving forward. We have developed ensitrelvir, an antiviral compound that targets the 3C-like protease of SARS-CoV-2. In this study, a delayed-treatment mouse model was used to clarify the potential in vivo efficacy of ensitrelvir.
METHODS
Female BALB/cAJcl mice of different ages were infected with the SARS-CoV-2 gamma strain (hCoV-19/Japan/TY7-501/2021) or mouse-adapted SARS-CoV-2 MA-P10 and then 24 h post-infection orally administered various doses of ensitrelvir or vehicle. Viral titres and RNA levels in the lungs were quantified using VeroE6/TMPRSS2 cells and RT-qPCR, respectively. Body weight loss, survival, lung weight, cytokine/chemokine production, nucleocapsid protein expression and lung pathology were evaluated to investigate the in vivo efficacy of ensitrelvir.
RESULTS
Based on infectious viral titres and viral RNA levels in the lungs of infected mice, ensitrelvir reduced viral loads in a dose-dependent manner. The antiviral efficacy correlated with increased survival, reduced body weight loss, reduced pulmonary lesions and suppression of inflammatory cytokine/chemokine levels.
CONCLUSIONS
This was the first evaluation of the in vivo anti-SARS-CoV-2 efficacy of ensitrelvir in a delayed-treatment mouse model. In this model, ensitrelvir demonstrated high antiviral potential and suppressed lung inflammation and lethality caused by SARS-CoV-2 infection. The findings support the continued clinical development of ensitrelvir as an antiviral agent to treat patients with COVID-19.
Topics: Animals; Female; Mice; Antiviral Agents; Chemokines; Cytokines; Disease Models, Animal; Lung; SARS-CoV-2; Weight Loss; COVID-19 Drug Treatment
PubMed: 35914182
DOI: 10.1093/jac/dkac257 -
Cells Jul 2022Respiratory infections with newly emerging zoonotic viruses such as SARS-CoV-2, the etiological agent of COVID-19, often lead to the perturbation of the human innate and... (Review)
Review
Respiratory infections with newly emerging zoonotic viruses such as SARS-CoV-2, the etiological agent of COVID-19, often lead to the perturbation of the human innate and adaptive immune responses causing severe disease with high mortality. The responsible mechanisms are commonly virus-specific and often include either over-activated or delayed local interferon responses, which facilitate efficient viral replication in the primary target organ, systemic viral spread, and rapid onset of organ-specific and harmful inflammatory responses. Despite the distinct replication strategies, human infections with SARS-CoV-2 and highly pathogenic avian influenza viruses demonstrate remarkable similarities and differences regarding the mechanisms of immune induction, disease dynamics, as well as the long-term sequelae, which will be discussed in this review. In addition, we will highlight some important lessons about the effectiveness of antiviral and immunomodulatory therapeutic strategies that this pandemic has taught us.
Topics: Animals; Antiviral Agents; COVID-19; Humans; Inflammation; Pandemics; SARS-CoV-2
PubMed: 35883640
DOI: 10.3390/cells11142198 -
Current Allergy and Asthma Reports Jan 2021Told from the viewpoint of rheumatologists, this review tells the story of hydroxychloroquine and its swift ascent to become a household name as a therapeutic strategy... (Review)
Review
PURPOSE OF REVIEW
Told from the viewpoint of rheumatologists, this review tells the story of hydroxychloroquine and its swift ascent to become a household name as a therapeutic strategy against the novel SARS-CoV-2 virus. This review describes the history, mechanisms, pharmacokinetics, therapeutic applications, and safety profile of hydroxychloroquine as an immunomodulatory and antiviral agent. It also summarizes the major studies that launched and assessed the use of hydroxychloroquine against COVID-19 infection.
RECENT FINDINGS
More recent literature calls into question the long-held dogma that endolysosomal alkalinization is the primary mode of action of hydroxychloroquine. Ongoing uncertainty about the multiple potential mechanisms contributing to the therapeutic effect of hydroxychloroquine in rheumatic and viral disease led to a natural avenue for exploration in the treatment of COVID-19. Taken as a whole, the literature does not support utilizing hydroxychloroquine to treat or prevent infection from the SARS-CoV-2 virus. This is, at least in part, due to the wide variability in hydroxychloroquine pharmacokinetics between patients and difficulty achieving adequate target tissue concentrations of hydroxychloroquine without encountering unacceptable toxicities. Hydroxychloroquine continues to be a routinely prescribed, well-tolerated, effective, and low-cost treatment for rheumatic disease. Its therapeutic versatility has led to frequent repurposing for other conditions, most recently as an investigative treatment against the SARS-CoV-2 virus. Despite overall negative findings, the intense study of hydroxychloroquine against COVID-19 infection has enhanced our overall understanding of how hydroxychloroquine operates in autoimmune disease and beyond.
Topics: Animals; Antiviral Agents; Humans; Hydroxychloroquine; Rheumatologists; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 33475900
DOI: 10.1007/s11882-020-00983-9