No approved-drug candidate for viral disease is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
RCSB Protein Data Bank · entry 4I79 · 1.75 Å · ligand UNKNOWN ATOM OR ION (UNX). Experimental structure, not a prediction.
Ribavirin showed in vitro activity against both neuraminidase inhibitor-sensitive and -resistant H7N9 influenza viruses, with a 50% effective virus-inhibitory concentration of 0.01–0.02 mg/mL (3–4 nmol) on MDCK epithelial cells, and was safe in vitro at roughly 300 times that concentration. In a mouse model using the NAI-sensitive A/Anhui/1/2013 strain, all nine placebo-treated animals died with weight loss over 35%, while all mice given ribavirin or zanamivir twice daily survived despite losing around 30% of body weight. Lung virus titres at three days post-infection were ten-fold lower in both treatment groups than in the placebo group, and ribavirin-treated mice had lower titres than zanamivir-treated animals, though the difference was not statistically significant. The authors concluded ribavirin was comparable to zanamivir against H7N9 and supported its use against NAI-resistant infections, noting intranasal administration was efficacious without the side effects of oral or intravenous routes.
A separate study of 176 patients with chronic hepatitis C virus genotype 1 receiving 48 weeks of peg-interferon plus ribavirin found a sustained virological response in 83 patients (47.2%). A predictive formula using simple clinical data achieved an area under the receiver operating characteristic curve of 0.821 at week 4, 0.802 at week 12, and 0.891 at week 24, but only 0.570 at baseline, meaning prediction was not possible before treatment started. The formula at week 48 reached 0.871 in validation, and prediction by the formula was always superior to that by viral kinetics alone.
A 2009 review of picornavirus life cycles described how viral capsid proteins interact with host cell receptors and how viral and host factors participate in replication, translation, and the switch from translation to RNA replication, suggesting that understanding these interactions could inform design of novel antiviral agents. A 2017 review of patented virus-based RNA silencing agents and virus-derived expression vectors concluded that despite recent advances, these developments had yet to be proven effective in clinical and field trials. A 1964 commentary noted that clinically useful agents were available for certain viral infections and that established viral disease could respond to drug treatment, while doubting that a single approach would suit all viral disease.
What remains missing is direct clinical evidence for ribavirin against H7N9 in humans, since the mouse data used only one strain and the NAI-resistant mutant was not tested in vivo due to its reversion to sensitivity and lower replication. The hepatitis C predictive formula needs prospective validation in other cohorts before it can guide individual therapy. No trial has yet shown that the intranasal ribavirin route protects people exposed to infected poultry, and the gene therapy vectors reviewed have not passed efficacy testing in patients.
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Biomedical Science · 2009 · 197 citations · open access
Viral and host proteins involved in picornavirus life cycle
AbstractPicornaviruses cause several diseases, not only in humans but also in various animal hosts. For instance, human enteroviruses can cause hand-foot-and-mouth disease, herpangina, myocarditis, acute flaccid paralysis, acute hemorrhagic conjunctivitis, severe neurological complications, including brainstem encephalitis, meningitis and poliomyelitis, and even death. The interaction between the virus and the host is important for viral replication, virulence and pathogenicity. This article reviews studies of the functions of viral and host factors that are involved in the life cycle of picornavirus. The interactions of viral capsid proteins with host cell receptors is discussed first, and the mechanisms by which the viral and host cell factors are involved in viral replication, viral translation and the switch from translation to RNA replication are then addressed. Understanding how cellular proteins interact with viral RNA or viral proteins, as well as the roles of each in viral infection, will provide insights for the design of novel antiviral agents based on these interactions.
https://doi.org/10.1186/1423-0127-16-103Protein & Cell · 2016 · 12 citations · open access
Ribavirin is effective against drug-resistant H7N9 influenza virus infections
AbstractDear Editor, In February and March 2013, a novel influenza A (H7N9) virus emerged in China, causing an acute respiratory distress syndrome and occasionally multiple organ failure with high fatality rates in humans (Li et al., 2014). A total of 681 laboratory-confirmed cases and 275 deaths have been reported as of November 13th, 2015, with a fatality rate of 40% (http://www.who.int/influenza/human_animal_interface/HAI_Risk_Assessment/en/). H7N9 has been evolving and established amongst chickens in China over the past two years with occasional human infections (Lam et al., 2015; Su et al., 2015), thus posing a threat to public health. In the absence of an annually-updated effective vaccine, antiviral drugs constitute the first line of defense against H7N9 infections. H7N9 viruses already possess natural resistance to M2-ion channel blockers (amantadine and rimantadine) when it first emerged in 2013 (Gao et al., 2013). Therefore neuraminidase inhibitors (NAIs), which include oseltamivir (TamifluH), zanamivir (RelenzaH) and peramivir constitute the main antiviral drugs against H7N9 infections (Hu et al., 2013; Wu et al., 2013). However, treatment with NAIs against H7N9 infections has resulted in the emergence of drug-resistant mutant viruses, as soon as 1~9 days after administration (Gao et al., 2013; Hu et al., 2013). Moreover, the first H7N9 isolate (A/Shanghai/1/2013(H7N9), SH-H7N9) was resistant to oseltamivir (Gao et al., 2013). It is therefore necessary to investigate whether other classes of drugs can control H7N9 infections. A recent study shows that the RNA polymerase 2 (PB2) gene of the H7N9 virus is critical for virulence in mammals (Bi et al., 2015). Ribavirin is a well-characterized, broad-spectrum nucleoside inhibitor used to halt the synthesis and capping of viral RNA and mRNA, respectively, by the viral RNA-dependent RNA polymerase (Crotty et al., 2000). Ribavirin is approved for treating infections with Hepatitis C virus and respiratory syncytial virus (Graci and Cameron, 2006). Moreover, ribavirin is effective by itself or in combination with NAIs and/or M2-ion channel blockers against H1N1, H3N2 and H5N1 influenza infections (Smee et al., 2005; Ilyushina et al., 2008; Nguyen et al., 2009). Here, we want to investigate whether ribavirin is effective by itself against H7N9 virus infections, especially to virus mutants that have developed resistance to NAIs. To compare the efficacy of ribavirin to that of NAIs, zanamivir was used as a positive control. To determine the effectiveness of the ribavirin against H7N9 viruses in vitro, NAI-sensitive (A/Anhui/1/2013, AH-H7N9) and -resistant (SH-H7N9) viruses were used in this study. The 50% effective virus-inhibitory concentration (EC50) value was used to evaluate the antiviral functions of ribavirin. Serial two-fold dilutions of ribavirin were used to test the EC50 against AH-H7N9 and SH-H7N9 on Madin-Darby Canine Kidney (MDCK) epithelial cells, respectively. The results showed that ribavirin was effective against both AH-H7N9 and SH-H7N9 with an EC50 of 0.01~0.02 mg/mL (3~4 nmol) (Table 1), implying that ribavirin could be utilized against both NAI-sensitive and -resistant H7N9 viruses. In addition, the ribavirin at a dose of ~300 folds of the calculated EC50 is also safe in vitro without significant cytotoxicity. EC50 values of ribavirin against H7N9 virus EC50 values of ribavirin against H7N9 virus In vitro studies showed that the ribavirin is effective to both the NAI-sensitive (AH-H7N9) and -resistant (SH-H7N9) viruses. To further study antiviral function in vivo, the efficacy of ribavirin against H7N9 infection was then tested in a mouse animal model. To confirm the antiviral functions of ribavirin, zanamivir was selected as a positive drug control. The survival, percentage weight change and clinical symptoms in the animals after challenge were monitored over the course of the experiment (14 days). All animals infected with AH-H7N9 displayed ruffled fur, loss of activity and body weight loss beginning 2 days post-infection (d.p.i.). Mice treated with placebo did not survive and had weight loss of over 35% (Fig. 1A and 1B). Mice treated with ribavirin or zanamivir also experienced weight loss of up to around 30%, but all mice in each group gradually recovered and survived (Fig. 1A and 1B). In general, the clinical signs of mice in the ribavirin and zanamivir groups were milder than that of the placebo group. No significant changes were observed from mice in the mock-infection group. Efficacy of ribavirin in mice infected with AH-H7N9. Mice (n = 9) were given ribavirin, zanamivir or PBS (placebo) twice daily, respectively. Animals were inoculated i.n. with 10× LD50 of AH-H7N9 in 50 µL PBS at one day after the initiation of treatment, and an untreated group was mock-challenged with an equal volume of PBS as control. Survival and body weights were monitored daily over a 14-day observation period and expressed as percentages of the initial values (A). The mortality rate was calculated from the survival curve of each group (B). Five mice from each group were euthanized at 3 d.p.i. LVTs were quantified in MDCK cells, and expressed as log10 TCID50/0.1 mL (C). The data are presented as the mean ± SD. Statistical analysis on the LVTs were performed with a paired-sample t-test (*, P < 0.05; **, P < 0.01; ***, P < 0.001) Five mice from each group were euthanized at 3 d.p.i. and the lung virus titers (LVTs) were test in MDCK cells, with the results presented as 50% tissue culture infective dose (TCID50). The results showed that the LVTs from mice treated with either the ribavirin or zanamivir were 10-fold lower than that of the sterile phosphate-buffered saline (PBS) placebo group (P < 0.5) (Fig. 1C). Interestingly, ribavirin-treated mice displayed lower LVTs than that of zanamivir-treated animals, but the values were not statistically significant (P > 0.5) (Fig. 1C). In conclusion, ribavirin displayed antiviral activities comparable to zanamivir against H7N9 virus infections in vitro and in vivo, and the data support the use of ribavirin against NAI-resistant H7N9 virus infections. Since it had been shown in previous studies that SH-H7N9 containing the NAI-resistant K224 mutation (H3 numbering) on the neuraminidase (NA) gene reverts back to the NAI-sensitive R224 mutation in vivo (Yen et al., 2014), as well as the relatively lower replication ability in vitro compared to AH-H7N9 (the NAI-sensitive virus) (Wu et al., 2013), only AH-H7N9 was used for the studies in mice. Notably, administration of ribavirin via the intranasal (i.n.) route was still efficacious against severe influenza virus infections without any of the negative side effects associated with oral or intravenous administration (Gilbert and McLeay, 2008). The present study showed that the i.n. route is also effective in the case of ribavirin against H7N9 virus infection. Human infections with H7N9 mainly originate from contact with infected poultry or contaminated materials in live poultry markets (Gao, 2014), and administration of ribavirin into the nasal mucosa would be an effective strategy to mitigate the risk of H7N9 infections in humans. The online version of this article (doi:10.1007/s13238-016-0287-0) contains supplementary material, which is available to authorized users. This work was supported by the National Basic Research Program (973 Program) (Nos. 2013CB531502 and 2014CB542503) and the National Natural Science Foundation of China (Grant No. 31402196). Yi Shi is supported by the Excellent Young Scientist Program of the Chinese Academy of Sciences and the Youth Innovation Promotion Association CAS (2015078). Gary Wong is the recipient of a Banting Postdoctoral Fellowship from the Canadian Institutes of Health Research (CIHR) and the President's International Fellowship Initiative from the Chinese Academy of Sciences (CAS). Ribavirin (National Drug Approval No. H20043189) was obtained from Penglai Nuokang Pharmaceutical Co., Ltd. (Penglai city, Shandong Province, China). Zanamivir carboxylate was purchased from Shandong Xiya Chemical Industry Co., Ltd. (Shandong Province, China). Yuhai Bi, Gary Wong, Yingxia Liu, Lei Liu, George F Gao and Yi Shi declare that they have no conflict of interest. All institutional and national guidelines for the care and use of laboratory animals were followed. Supplemental Materials
https://doi.org/10.1007/s13238-016-0287-0PubMed · 2010 · 2 citations
On-treatment predictions of success in peg-interferon/ribavirin treatment using a novel formula.
AbstractAIM: To predict treatment success using only simple clinical data from peg-interferon plus ribavirin therapy for chronic hepatitis C. METHODS: We analyzed the clinical data of 176 patients with chronic hepatitis and hepatitis C virus genotype 1 who received 48 wk standard therapy, derived a predictive formula to assess a sustained virological response of the individual patient using a logistic regression model and confirmed the validity of this formula. The formula was constructed using data from the first 100 patients enrolled and validated using data from the remaining 76 patients. RESULTS: Sustained virological response was obtained in 83 (47.2%) of the patients and we derived formulae to predict sustained virological response at pretreatment and weeks 4, 12 and 24. The likelihood of sustained virological response could be predicted effectively by the formulae at weeks 4, 12 and 24 (the area under the curve of the receiver operating characteristic: 0.821, 0.802, and 0.891, respectively), but not at baseline (0.570). The formula at week 48 was also constructed and validation by test data achieved good prediction with 0.871 of the area under the curve of the receiver operating characteristic. Prediction by this formula was always superior to that by viral kinetics. CONCLUSION: These results suggested that our formula combined with viral kinetics provides a clear direction of therapy for each patient and enables the best tailored treatment.
https://doi.org/10.3748/wjg.v16.i1.89Recent Patents on Biotechnology · 2017 · 1 citations
Virus-Based RNA Silencing Agents and Virus-Derived Expression Vectors as Gene Therapy Vehicles
AbstractBACKGROUND: In consideration of recent developments in understanding the genomics and proteomics of viruses, the use of viral DNA / RNA sequences as well as their gene expression schemes, have found new in-roads towards the prognosis and therapy of diseases. Correspondingly, the sphere of the patenting scenario has expanded significantly. OBJECTIVES: The current review addresses patented inventions concerning the use of virus sequences as gene silencing machineries and inventions concerning the generation and application of viral sequences as expression vectors. Furthermore, this review also discusses the employment of these patents for clinical, agricultural and biotechnological applications. METHOD: Considering these objectives, the Delphion Research Intellectual Property Network database was searched using keywords such as "gene silencing", "engineered viruses" and "expression vectors" and descriptions of recent patents on the said topics were discussed. CONCLUSION: Despite several recent advances in the use of viruses as disease therapy vehicles and biotechnological vectors, these developments have yet to be proven effective in practice, in clinical and field trials.
https://doi.org/10.2174/1872208311666170301103722Clinical Infectious Diseases · 1998 · 0 citations
Pathophysiology of Viruses and Viral Diseases
AbstractAbstract Medical virology seeks to understand the pathogenesis and therapy of viral agents infectious for humans. Molecular detection systems, serology, electron microscopy, cell culture, and animal models have revealed an amazing diversity and specificity in the pathogenesis of viral infections. Every virus-host relationship has new lessons to teach us, and generalizations are becoming less and less possible as our analytic tools improve. However, certain broad themes have stood the test of time. This chapter will present a general overview of viral pathogenesis at the cell and organism level, introducing concepts developed in detail in discussions of individual agents and clinical syndromes.
https://doi.org/10.1093/oso/9780195081039.003.0004Expert Opinion on Drug Safety · 1993 · 0 citations
Etude et réalisation d'un système de détection électromagnétique de survie
AbstractEvery patient will experience adverse effects to differing degrees; a systematic approach to their management can be very helpful. Early recognition and intervention can help clinicians ensure that patients are able to complete therapy where possible and achieve the goal of viral eradication. Treatment with the next generation of antivirals will improve safety and efficacy.
https://doi.org/10.1517/14740338.2014.884068Postgraduate Medicine · 1964 · 0 citations
The Future for Drug Treatment of Viral Disease
AbstractClinically useful agents are now available for certain viral infections, and great hope can be based on the fact that established viral disease will respond to drug treatment. The belief that virus vaccines can be the only solution to viral disease may be weakening slightly. Some alternatives to vaccines might be in order. It seems unlikely that a single approach will be suitable against all viral disease.
https://doi.org/10.1080/00325481.1964.11695121Greater South Information System · 2018 · 0 citations · open access
Introduction
AbstractViruses have played a major role in 20th-century Biology and continue to serve as ideal tools for the dissection of the most intricate life processes. Initially, much of the early studies were focused on deciphering the nature of these unique entities, their interactions with hosts and pathogenesis. Much of what has been learnt proved applicable to understanding of the nature and structure of genes, how genes and genomes operate and how genetic information is replicated over generations. Scientists have since rapidly harnessed the biology of the viruses for the development of new tools and applications in molecular biology, medicine, and agriculture. It is interesting that the very traits employed by viruses to establish infection and induce disease in their hosts are now being manipulated for the production of vectors and biologics that are safe and efficacious. Indeed the convergence of biology, genetics, biochemistry, and physics has propelled the development of molecular biology and advanced the field of Virology, culminating with the realization that viruses are ancient, the most diverse and uncharacterized components of the major ecosystems on Earth, that might also have played a major part in the emergence and consequent structure of modern cellular life.
https://doi.org/10.60692/04rez-tg758Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works using Disease Ontology synonyms, resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
