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Molecular Pharmaceutics Jun 2021The ongoing pandemic of global concern has killed about three million humans and affected around 151 million people worldwide, as of April 30, 2021. Although recently... (Review)
Review
The ongoing pandemic of global concern has killed about three million humans and affected around 151 million people worldwide, as of April 30, 2021. Although recently approved vaccines for COVID-19 are engendering hope, finding new ways to cure the viral pandemic is still a quest for researchers worldwide. Major pandemics in history have been of viral origin, such as SARS, MERS, H1NI, Spanish flu, and so on. A larger emphasis has been on discovering potential vaccines, novel antiviral drugs, and agents that can mitigate the viral infection symptoms; however, a relatively new area, RNA interference (RNAi), has proven effective as an antiviral agent. The RNAi phenomenon has been largely exploited to cure cancer, neurodegenerative diseases, and some rare diseases. The U.S. Food and Drug Administration has recently approved three siRNA products for human use that garner significant hope in siRNA therapeutics for coronaviruses. There have been some commentaries and communications addressing this area. We have summarized and illustrated the significance and the potential of the siRNA therapeutics available as of April 30, 2021 to combat the ongoing viral pandemic and the emerging new variants such as B.1.1.7 and B.1.351. Numerous successful studies and several investigations to address the clinical application of siRNA therapeutics provide great hope in this field. This seminal Review describes the significance of siRNA-based therapy to treat diverse viral infections in addition to the current coronavirus challenge. In addition, we have thoroughly reviewed the patents approved for coronaviruses, the major challenges in siRNA therapy, and the potential approaches to address them, followed by innovation and prospects.
Topics: Antiviral Agents; COVID-19; Clinical Trials as Topic; Drug Approval; Drug Evaluation, Preclinical; History, 20th Century; History, 21st Century; Humans; Mutation; Pandemics; Patents as Topic; RNA, Small Interfering; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 33945284
DOI: 10.1021/acs.molpharmaceut.0c01239 -
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 -
Journal of Drugs in Dermatology : JDD Jul 2023
Topics: Humans; Antiviral Agents; Nitric Oxide; Dermatologists
PubMed: 37410052
DOI: No ID Found -
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 -
Anti-inflammatory & Anti-allergy Agents... 2023The role of herbal medicines in the treatment of viruses and the identification of potential antiviral drugs has been the focus of researchers for decades. The control... (Review)
Review
The role of herbal medicines in the treatment of viruses and the identification of potential antiviral drugs has been the focus of researchers for decades. The control and treatment of viral diseases are very important due to the evolution of viruses and the emergence of new viruses compared to other pathogens such as fungi and bacteria. (AM) is a significant medicinal plant. The potential use of this plant and its chemical components in the treatment of inflammatory illnesses and viral diseases has been vigorously researched recently. polysaccharides (APS) make up the majority of AM's ingredients. The main mechanisms of the antiviral effect of APS have been investigated in some studies. The results of these studies show that APS can exert its antiviral effect by enhancing type I IFN signaling, inhibiting the expression of Bax and Caspase-3 proteins in the apoptosis pathway, and other antiviral mechanisms such as anti-inflammatory activities. The most well-known inflammatory products of APS's antiviral effects are B-cell proliferation, antibody products, nuclear factor-kappa B (NF-κB), and IL(s). Although it has a known effectiveness, there are some limitations to this substance's use as medicine. The use of nanotechnology is removing these limitations and its ability to be used as an anti-virus agent. The purpose of this review is to emphasize the role of AM, especially APS, in controlling inflammatory pathways in the treatment of viral infections. With the emergence of these herbal medications, a new path has been opened in the control and treatment of viral infections.
Topics: Astragalus propinquus; Signal Transduction; Anti-Inflammatory Agents; Plants, Medicinal; Antiviral Agents; Virus Diseases; Polysaccharides
PubMed: 38115620
DOI: 10.2174/0118715230280333231207114927 -
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 -
Expert Opinion on Pharmacotherapy Dec 2022The pathogenesis of severe COVID-19 is due, in part, to dysregulation of the human immune system in response to SARS-CoV-2 infection. Immune cells infected with...
INTRODUCTION
The pathogenesis of severe COVID-19 is due, in part, to dysregulation of the human immune system in response to SARS-CoV-2 infection. Immune cells infected with SARS-CoV-2 can trigger a hyperinflammatory response of both the adaptive and innate immune system that has been associated with severe disease, hospitalization, and death, and better treatment options are urgently needed.
AREAS COVERED
A mainstay of therapy for COVID-19 involves an antiviral agent, remdesivir, in combination with a systemic corticosteroid, dexamethasone.
EXPERT OPINION
The addition of a second immunomodulator, such as an interleukin-6 inhibitor or a Janus kinase inhibitor, has been associated with clinical benefit in a subset of patients with moderate-to-severe disease, but their use remains controversial. This manuscript reviews what is known about the approach to treatment of severe COVID-19 and examines how immunomodulators such as infliximab and abatacept may alter clinical management and COVID-19 research in the years ahead based on the results of randomized, controlled trials.
Topics: Humans; SARS-CoV-2; Antiviral Agents; Hospitalization; COVID-19 Drug Treatment
PubMed: 36271630
DOI: 10.1080/14656566.2022.2140041 -
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