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Scientific Reports May 2019Hepatitis C virus (HCV) is the major causative agent of chronic liver diseases, including liver cirrhosis and hepatocellular carcinoma. The recent development of highly...
Hepatitis C virus (HCV) is the major causative agent of chronic liver diseases, including liver cirrhosis and hepatocellular carcinoma. The recent development of highly effective direct-acting antivirals (DAAs) has revolutionized the treatment of HCV patients. However, these DAAs are exorbitantly expensive for the majority of HCV patients worldwide. Moreover, these drugs still show genotypic difference in cure rate and have some resistant-associated variants. Tylophorine, a natural compound derived from Tylophora indica plants, is known to have anti-inflammatory and anti-cancerous growth activities. In the present study, we showed that two tylophorine intermediates, 5-Oxo-1-[(2,3,6,7-tetramethoxy-9-phenanthrenyl) methyl]-L-proline (O859585) and 2,3,6,7-tetramethoxy-9-phenanthrenecarboxylic acid (T298875), displayed anti-HCV activity with an EC of 38.25 µM for T298875 and 29.11~35.3 µM for O859585 in various HCV genotypes. We demonstrated that O859585 efficiently blocked HCV attachment by neutralizing free viral particles without affecting other stages of the HCV life cycle and interferon stimulation. O859585 interrupted binding between HCV E2 and CD81. Of note, co-treatment of O859585 with either interferon alpha (IFNα) or sofosbuvir exerted either an additive or synergistic antiviral activity in HCV-infected cells with no measurable effect on cell viability. Most importantly, O859585 in combination with IFNα and sofosbuvir exhibited synergistic effects on anti-HCV activity in primary human hepatocytes. Collectively, these data suggest that O859585 may be a novel antiviral agent for HCV therapy.
Topics: Alkaloids; Antiviral Agents; Cell Line, Tumor; Cell Survival; Drug Synergism; Drug Therapy, Combination; HEK293 Cells; Hepacivirus; Hepatitis C, Chronic; Hepatocytes; Humans; Indolizines; Interferon-alpha; Phenanthrenes; Primary Cell Culture; Proline; Sofosbuvir; Tetraspanin 28; Tylophora; Viral Envelope Proteins; Virus Internalization
PubMed: 31086268
DOI: 10.1038/s41598-019-43783-6 -
Poultry Science May 2023Duck plague virus (DPV) is a typical DNA virus of waterfowl, it causes huge economic losses to the duck industry due to the higher mortality and lower egg production....
Duck plague virus (DPV) is a typical DNA virus of waterfowl, it causes huge economic losses to the duck industry due to the higher mortality and lower egg production. The disease is one of the frequent epidemics and outbreaks on duck farms because present vaccines could not provide complete immunity and there are no specific antiviral drugs available. Therefore, the development of antiviral drugs is urgently needed. In this study, we evaluated the antiviral activity of BX795, a specific kinase inhibitor of 3-phosphoinositide-dependent kinase 1 (PDK1), protein kinase B (AKT) and Tank binding kinase 1 (TBK1), against DPV in different duck cells. Our study demonstrated that BX795 reveals prominent antiviral activity in a dose-dependent manner in different types of duck cells. Time-addition and antiviral duration analysis uncovered that BX795 inhibits viral infection therapeutically and its antiviral activity lasts longer than 96 h. Further studies have shown that BX795 prevents cell-to-cell spread of the DPV rather than affects other stage of viral life cycle. Mechanistically, BX795 can inhibit DPV US3 kinase activity, reduce the phosphorylation of US3 substrates, and prevent the interaction between US3 and UL47. Taking together, our study demonstrated BX795, which disrupts the viral kinase activity, is a candidate antiviral agent for DPV.
Topics: Animals; Ducks; Chickens; Antineoplastic Agents; Antiviral Agents
PubMed: 36931072
DOI: 10.1016/j.psj.2023.102597 -
International Journal of Nanomedicine 2023The ongoing SARS-CoV-2 pandemic has affected public health, the economy, and society. This study reported a nanotechnology-based strategy to enhance the antiviral...
INTRODUCTION
The ongoing SARS-CoV-2 pandemic has affected public health, the economy, and society. This study reported a nanotechnology-based strategy to enhance the antiviral efficacy of the antiviral agent remdesivir (RDS).
RESULTS
We developed a nanosized spherical RDS-NLC in which the RDS was encapsulated in an amorphous form. The RDS-NLC significantly potentiated the antiviral efficacy of RDS against SARS-CoV-2 and its variants (alpha, beta, and delta). Our study revealed that NLC technology improved the antiviral effect of RDS against SARS-CoV-2 by enhancing the cellular uptake of RDS and reducing SARS-CoV-2 entry in cells. These improvements resulted in a 211% increase in the bioavailability of RDS.
CONCLUSION
Thus, the application of NLC against SARS-CoV-2 may be a beneficial strategy to improve the antiviral effects of antiviral agents.
Topics: Humans; SARS-CoV-2; Antiviral Agents; COVID-19; COVID-19 Drug Treatment; Lipids
PubMed: 37007987
DOI: 10.2147/IJN.S391462 -
Biometals : An International Journal on... Feb 2023SARS-CoV-2 is a highly infectious virus and etiologic agent of COVID-19, which is spread by respiratory droplets, aerosols, and contaminated surfaces. Copper is a known...
SARS-CoV-2 is a highly infectious virus and etiologic agent of COVID-19, which is spread by respiratory droplets, aerosols, and contaminated surfaces. Copper is a known antiviral agent, and has resulted in successful reduction of pathogens and infections by 83-99.9% when coated on surfaces in intensive care units. Additionally, copper has been shown to inactivate pathogens such as Coronavirus 226E, a close relative of SARS-CoV-2. Here, we examine the ability of two copper blends with differing compositions to inactivate SARS-CoV-2 virus at different time points. Copper Blend 2 (75.07% pure copper) was found to significantly reduce (over 50%) the viability of SARS-CoV-2 at 5 min of contact, with at least 98% reduction in recovered virus at 20 min (vs. plastic control). However, Copper Blend 1 (48.26% pure copper), was not found to significantly reduce viability of SARS-CoV-2 at any time point when compared to plastic. This may indicate that there is an important percentage of copper content in materials that is needed to effectively inactivate SARS-CoV-2. Overall, this study shows that over the course of 20 min, coatings made of copper materials can significantly reduce the recovery of infectious SARS-CoV-2 compared to uncoated controls, indicating the effective use of copper for viral inactivation on surfaces. Furthermore, it may suggest higher copper content has stronger antiviral properties. This could have important implications when short turnaround times are needed for cleaning and disinfecting rooms or equipment, especially in strained healthcare settings which are struggling to keep up with demand.
Topics: Humans; SARS-CoV-2; COVID-19; Copper; Antiviral Agents; Plastics
PubMed: 36474101
DOI: 10.1007/s10534-022-00473-7 -
MMWR. Morbidity and Mortality Weekly... Jan 2008Influenza is a major cause of morbidity and mortality in the United States, with an average of 36,000 deaths attributed to the disease annually. Patients with...
Influenza is a major cause of morbidity and mortality in the United States, with an average of 36,000 deaths attributed to the disease annually. Patients with influenza-like illness (ILI) often are evaluated by their primary-care physicians (PCPs). Antiviral therapy initiated within 48 hours of ILI symptom onset can shorten the course of influenza illness; antiviral therapy also is used as chemoprophylaxis for influenza, particularly in institutions and communities. Early laboratory diagnosis and knowing when influenza is circulating in the community can guide effective clinical management. To assess influenza-testing and antiviral-agent prescribing practices during the 2006-07 influenza season, personnel at four of 10 Emerging Infections Program (EIP) sites with influenza hospitalization surveillance surveyed PCPs. This report describes the results of that survey, which indicated that 69.0% of the PCPs administered influenza tests to patients who had ILI during the influenza season and 53.8% prescribed antiviral agents, including two (i.e., amantadine and rimantadine) no longer recommended by CDC. Health agencies, medical societies, and continuing medical education organizations should advance programs for physicians that increase awareness of recommendations regarding appropriate influenza testing and use of antiviral agents.
Topics: Antiviral Agents; Clinical Laboratory Techniques; Connecticut; Drug Utilization; Family Practice; Health Care Surveys; Humans; Influenza, Human; Minnesota; New Mexico; New York; Practice Patterns, Physicians'; Seasons
PubMed: 18219266
DOI: No ID Found -
Viruses Dec 2022Foot-and-mouth disease virus (FMDV), an economically important pathogen of cloven-hoofed livestock, is a positive-sense, single-stranded RNA virus classified in the...
Foot-and-mouth disease virus (FMDV), an economically important pathogen of cloven-hoofed livestock, is a positive-sense, single-stranded RNA virus classified in the family. RNA-dependent RNA polymerase (RdRp) of RNA viruses is highly conserved. Compounds that bind to the RdRp active site can block viral replication. Herein, we combined double virtual screenings and cell-based antiviral approaches to screen and identify potential inhibitors targeting FMDV RdRp (3D). From 5596 compounds, the blind- followed by focus-docking filtered 21 candidates fitting in the 3D active sites. Using the BHK-21 cell-based assay, we found that four compounds-NSC217697 (quinoline), NSC670283 (spiro compound), NSC292567 (nigericin), and NSC65850-demonstrated dose-dependent antiviral actions in vitro with the EC50 ranging from 0.78 to 3.49 µM. These compounds could significantly block FMDV 3D activity in the cell-based 3D inhibition assay with small IC50 values ranging from 0.8 nM to 0.22 µM without an effect on FMDV's main protease, 3C. The 3D inhibition activities of the compounds were consistent with the decreased viral load and negative-stranded RNA production in a dose-dependent manner. Conclusively, we have identified potential FMDV 3D inhibitors that bound within the enzyme active sites and blocked viral replication. These compounds might be beneficial for FMDV or other picornavirus treatment.
Topics: Animals; Foot-and-Mouth Disease Virus; Antiviral Agents; RNA-Dependent RNA Polymerase; Foot-and-Mouth Disease; Virus Replication
PubMed: 36680163
DOI: 10.3390/v15010124 -
Journal of Applied Microbiology Jan 2022Chitosan is an abundant organic polysaccharide, which can be relatively easily obtained by chemical modification of animal or fungal source materials. Chitosan and its... (Review)
Review
Chitosan is an abundant organic polysaccharide, which can be relatively easily obtained by chemical modification of animal or fungal source materials. Chitosan and its derivatives have been shown to exhibit direct antiviral activity, to be useful vaccine adjuvants and to have potential anti-SARS-CoV-2 activity. This thorough and timely review looks at the recent history of investigations into the role of chitosan and its derivatives as an antiviral agent and proposes a future application in the treatment of endemic SARS-CoV-2.
Topics: Adjuvants, Vaccine; Animals; Antiviral Agents; COVID-19; Chitosan; Humans; SARS-CoV-2
PubMed: 34218488
DOI: 10.1111/jam.15202 -
Journal of Infection and Chemotherapy :... Feb 2023Favipiravir, an antiviral agent with activity against SARS-CoV-2, was made available to hospitals in Japan for off-label use among COVID-19 patients between 2020 and... (Observational Study)
Observational Study
INTRODUCTION
Favipiravir, an antiviral agent with activity against SARS-CoV-2, was made available to hospitals in Japan for off-label use among COVID-19 patients between 2020 and 2021.
METHODS
A nationwide observational cohort study was conducted on patients who received favipiravir as part of clinical care between February 2020 and December 2021. Information was collected on demographics, comorbidities, severity of illness, use of favipiravir and other medications targeting COVID-19, adverse events, clinical status at 7 and 14 days and clinical outcome one month after admission to the hospital.
RESULTS
A total of 17,508 hospitalized patients who received favipiravir were registered from 884 hospitals. In terms of demographics, 55.9% were age ≥60 years, and 62.3% were male. At least one of the four surveyed comorbidities was present in 45.5% of the patients. The rates of clinical improvement at 7 and 14 days were 72.4% and 87.5%, 61.4% and 76.6%, and 45.4% and 59.5% for mild, moderate, and severe diseases, respectively. The case fatality rates within a month from hospitalization were 3.3%, 12.6%, and 29.1% for mild, moderate, and severe diseases, respectively. Significant correlations were observed between death and advanced age, male sex, moderate or severe disease, diabetes, cardiovascular diseases, and immunosuppression. Commonly reported adverse events included uric acid level increase or hyperuricemia (16.8%), liver function abnormalities (6.9%), and rash (1.0%).
CONCLUSIONS
Favipiravir was well tolerated among COVID-19 patients. The study provides insights into the use of this agent at hospitals across Japan in the early phase of the pandemic.
Topics: Humans; Male; Middle Aged; Female; COVID-19; SARS-CoV-2; Amides; Antiviral Agents; Cohort Studies; Treatment Outcome
PubMed: 36307058
DOI: 10.1016/j.jiac.2022.10.008 -
Indian Journal of Pharmacology 2023Novel SARS-CoV-2 (COVID-19) is affecting worldwide as declared pandemic by the WHO. Various repositioning and novel therapeutic agents are being evaluated under... (Review)
Review
Novel SARS-CoV-2 (COVID-19) is affecting worldwide as declared pandemic by the WHO. Various repositioning and novel therapeutic agents are being evaluated under different clinical setups; however, there is no promising therapeutic agent reported to date. Small molecules like peptides have their popularity as their specificity, delivery, and synthesizability as promising therapeutic agents. In this study, we have reviewed the published literature describing peptide designing, in silico binding mode, antiviral activity, preventive measures, and in vivo assessments. Here, we reported all the results which are promising against SARS-CoV-2 as therapeutic and preventive (vaccine candidates), and their status in the drug development process.
Topics: Humans; COVID-19; SARS-CoV-2; Peptidomimetics; Drug Repositioning; Antiviral Agents; Peptides
PubMed: 36960521
DOI: 10.4103/ijp.ijp_700_22 -
Theranostics 2017The influenza pandemic is a major threat to human health, and highly aggressive strains such as H1N1, H5N1 and H7N9 have emphasized the need for therapeutic strategies... (Review)
Review
The influenza pandemic is a major threat to human health, and highly aggressive strains such as H1N1, H5N1 and H7N9 have emphasized the need for therapeutic strategies to combat these pathogens. Influenza anti-viral agents, especially active small molecular inhibitors play important roles in controlling pandemics while vaccines are developed. Currently, only a few drugs, which function as influenza neuraminidase (NA) inhibitors and M2 ion channel protein inhibitors, are approved in clinical. However, the acquired resistance against current anti-influenza drugs and the emerging mutations of influenza virus itself remain the major challenging unmet medical needs for influenza treatment. It is highly desirable to identify novel anti-influenza agents. This paper reviews the progress of small molecular inhibitors act as antiviral agents, which include hemagglutinin (HA) inhibitors, RNA-dependent RNA polymerase (RdRp) inhibitors, NA inhibitors and M2 ion channel protein inhibitors etc. Moreover, we also summarize new, recently reported potential targets and discuss strategies for the development of new anti-influenza virus drugs.
Topics: Animals; Antiviral Agents; Drug Discovery; Humans; Orthomyxoviridae
PubMed: 28382157
DOI: 10.7150/thno.17071