scholarly journals Antiviral therapy: current concepts and practices.

1992 ◽  
Vol 5 (2) ◽  
pp. 146-182 ◽  
Author(s):  
B Bean
Keyword(s):  
Antiviral Therapy ◽  
Respiratory Infections ◽  
Antiviral Agents ◽  
Antiviral Drugs ◽  
Virus Infections ◽  
Immunodeficiency Virus ◽  
Viral Respiratory Infections ◽  
Toxic Drugs ◽  
Viral Respiratory

Drugs capable of inhibiting viruses in vitro were described in the 1950s, but real progress was not made until the 1970s, when agents capable of inhibiting virus-specific enzymes were first identified. The last decade has seen rapid progress in both our understanding of antiviral therapy and the number of antiviral agents on the market. Amantadine and ribavirin are available for treatment of viral respiratory infections. Vidarabine, acyclovir, ganciclovir, and foscarnet are used for systemic treatment of herpesvirus infections, while ophthalmic preparations of idoxuridine, trifluorothymidine, and vidarabine are available for herpes keratitis. For treatment of human immunodeficiency virus infections, zidovudine and didanosine are used. Immunomodulators, such as interferons and colony-stimulating factors, and immunoglobulins are being used increasingly for viral illnesses. While resistance to antiviral drugs has been seen, especially among AIDS patients, it has not become widespread and is being intensely studied. Increasingly, combinations of agents are being used: to achieve synergistic inhibition of viruses, to delay or prevent resistance, and to decrease dosages of toxic drugs. New approaches, such as liposomes carrying antiviral drugs and computer-aided drug design, are exciting and promising prospects for the future.

scholarly journals COVID-19 mitigation strategies were associated with decreases in other respiratory virus infections

2021 ◽  
Author(s):  
Sinha Pranay ◽  
Katherine Reifler ◽  
Michael Rossi ◽  
Manish Sagar
Keyword(s):  
Respiratory Virus ◽  
Respiratory Infections ◽  
Respiratory Viruses ◽  
Mitigation Strategies ◽  
Virus Infections ◽  
Time Period ◽  
Viral Respiratory Infections ◽  
Respiratory Virus Infections ◽  
Viral Respiratory

Abstract Detection of diverse respiratory viruses in Boston was around 80% lower after practices were instituted to limit COVID-19 spread compared to the same time period during the previous five years. Continuing the strategies that lower COVID-19 dissemination may be useful in decreasing the incidence of other viral respiratory infections.

scholarly journals Viral Determinants of Resistance to Treatment in Patients with Hepatitis C

2007 ◽  
Vol 20 (1) ◽  
pp. 23-38 ◽  
Author(s):  
Anette Wohnsland ◽  
Wolf Peter Hofmann ◽  
Christoph Sarrazin
Keyword(s):  
Hepatitis C ◽  
Antiviral Therapy ◽  
Phase 1 ◽  
Treatment Success ◽  
Antiviral Agents ◽  
Antiviral Drugs ◽  
Immune Defense ◽  
Phenotypic Resistance

SUMMARY Chronic hepatitis C virus (HCV) infection affects more than 170 million persons worldwide and is responsible for the development of liver cirrhosis in many cases. Standard treatment with pegylated alpha interferon (IFN-α) in combination with the nucleoside analogue ribavirin leads to a sustained virologic response in approximately half of the patients. IFN-α is classified as an indirect treatment, as it interacts with the host's immune response. The mechanism of action of ribavirin is still unknown. The benefit of triple therapy by adding other antiviral agents, e.g., amantadine, is controversial. Currently, new direct antiviral drugs (HCV protease/polymerase inhibitors) are being evaluated in phase 1/phase 2 trials. Phenotypic resistance to antiviral therapy has been attributed to amino acid variations within distinct regions of the HCV polyprotein. While sensitivity to IFN-α-based antiviral therapy in vivo is clearly correlated with the number of mutations within the HCV NS5A protein, the underlying functional mechanisms for this association are unknown. In turn, in vitro, several mechanisms to circumvent the host immune defense or to block treatment-induced antiviral activities have been described for different HCV proteins. By the introduction of direct antiviral drugs, hepatitis C therapy now is entering a new era in which the development of resistance may become the most important parameter for treatment success or failure.

scholarly journals Severe viral respiratory infections in children with IFIH1 loss-of-function mutations

2017 ◽  
Vol 114 (31) ◽  
pp. 8342-8347 ◽  
Author(s):  
Samira Asgari ◽  
Luregn J. Schlapbach ◽  
Stéphanie Anchisi ◽  
Christian Hammer ◽  
Istvan Bartha ◽  
...  
Keyword(s):  
Respiratory Infections ◽  
In Vitro Assays ◽  
Severe Illness ◽  
Healthy Children ◽  
Loss Of Function ◽  
Life Threatening ◽  
Syncytial Virus ◽  
Viral Respiratory Infections ◽  
Viral Respiratory

Viral respiratory infections are usually mild and self-limiting; still they exceptionally result in life-threatening infections in previously healthy children. To investigate a potential genetic cause, we recruited 120 previously healthy children requiring support in intensive care because of a severe illness caused by a respiratory virus. Using exome and transcriptome sequencing, we identified and characterized three rare loss-of-function variants in IFIH1, which encodes an RIG-I-like receptor involved in the sensing of viral RNA. Functional testing of the variants IFIH1 alleles demonstrated that the resulting proteins are unable to induce IFN-β, are intrinsically less stable than wild-type IFIH1, and lack ATPase activity. In vitro assays showed that IFIH1 effectively restricts replication of human respiratory syncytial virus and rhinoviruses. We conclude that IFIH1 deficiency causes a primary immunodeficiency manifested in extreme susceptibility to common respiratory RNA viruses.

scholarly journals Iota-carrageenan prevents the replication of SARS-CoV-2 on an in vitro respiratory epithelium model

2021 ◽  
Author(s):  
Augusto Varese ◽  
Ana Ceballos ◽  
Carlos Palacios ◽  
Juan Manuel Figueroa ◽  
Andrea Vanesa Dugour
Keyword(s):  
Sodium Chloride ◽  
Antiviral Activity ◽  
Nasal Spray ◽  
Respiratory Infections ◽  
Respiratory Epithelium ◽  
Model Cell ◽  
Human Use ◽  
Viral Respiratory Infections ◽  
Viral Respiratory

AbstractThere are, except for remdesivir, no approved antivirals for the treatment or prevention of SARS-CoV-2 infections. Iota-carrageenan formulated into a nasal spray has already been proven safe and effective in viral respiratory infections. We explored this antiviral activity in Calu-3, a human respiratory model cell line. A formula of iota-carrageenan and sodium chloride, as a nasal spray, already approved for human use, effectively inhibited SARS-CoV-2 infection in vitro, providing a more substantial reference for further clinical studies or developments.

scholarly journals Griffithsin-Modified Electrospun Fibers as a Delivery Scaffold To Prevent HIV Infection

2016 ◽  
Vol 60 (11) ◽  
pp. 6518-6531 ◽  
Author(s):  
Tiffany N. Grooms ◽  
Hung R. Vuong ◽  
Kevin M. Tyo ◽  
Danial A. Malik ◽  
Lee B. Sims ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Antiviral Agents ◽  
Electrospun Fibers ◽  
Virus Infections ◽  
Sexually Transmitted ◽  
Treatment Regimens ◽  
Potent Inhibition ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACTDespite current prophylactic strategies, sexually transmitted infections (STIs) remain significant contributors to global health challenges, spurring the development of new multipurpose delivery technologies to protect individuals from and treat virus infections. However, there are few methods currently available to prevent and no method to date that cures human immunodeficiency virus (HIV) infection or combinations of STIs. While current oral and topical preexposure prophylaxes have protected against HIV infection, they have primarily relied on antiretrovirals (ARVs) to inhibit infection. Yet continued challenges with ARVs include user adherence to daily treatment regimens and the potential toxicity and antiviral resistance associated with chronic use. The integration of new biological agents may avert some of these adverse effects while also providing new mechanisms to prevent infection. Of the biologic-based antivirals, griffithsin (GRFT) has demonstrated potent inhibition of HIV-1 (and a multitude of other viruses) by adhering to and inactivating HIV-1 immediately upon contact. In parallel with the development of GRFT, electrospun fibers (EFs) have emerged as a promising platform for the delivery of agents active against HIV infection. In the study described here, our goal was to extend the mechanistic diversity of active agents and electrospun fibers by incorporating the biologic GRFT on the EF surface rather than within the EFs to inactivate HIV prior to cellular entry. We fabricated and characterized GRFT-modified EFs (GRFT-EFs) with different surface modification densities of GRFT and demonstrated their safety and efficacy against HIV-1 infectionin vitro. We believe that EFs are a unique platform that may be enhanced by incorporation of additional antiviral agents to prevent STIs via multiple mechanisms.

scholarly journals Umifenovir and coronavirus infections: a review of research results and clinical practice

2020 ◽  
Vol 92 (11) ◽  
pp. 91-97
Author(s):  
I. A. Leneva ◽  
N. Y. Pshenichnaya ◽  
V. A. Bulgakova
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Antiviral Therapy ◽  
Respiratory Infections ◽  
Clinical Investigation ◽  
Meta Analysis ◽  
Antiviral Agent ◽  
Antiviral Drugs ◽  
Virus Elimination

Coronaviruses are known to cause acute respiratory infections. Antiviral therapy, including for COVID-19, is based on clinical practice, experimental data and trial results. The purpose of this review is to: provide and systematize actual preclinical data, clinical trials results and clinical practice for antiviral agent umifenovir (Arbidol). Databases Scopus, Web of Science, RSCI and medRxiv were used for publication searching from 2004. A meta-analysis of clinical trials results was performed. Umifenovir is antiviral agent, it belongs to fusion inhibitors, interacts with SARS-CoV-2 spike protein. Umifenovir the impede the trimerization of spike glycoprotein and inhibit host cell adhesion, at the level of the coronaviruses S-protein of interaction with ACE2 receptor. Preclinical studies in vitro and on animals show umifenovir activity against a number of coronaviruses, including SARS-CoV, MERS-CoV, SARS-CoV-2, and others. Umifenovir, in combination with other antiviral drugs, symptomatic or traditional medicine, was used in China to treat patients with COVID-19, resulting in reduced mortality, virus elimination, the frequency of more severe course and complications in middle severity. However, antiviral therapy for the treatment of severe patients, with ARDS, did not lead to improved outcomes. In comparative clinical studies, umifenovir showed similar effectiveness with other antiviral drugs, and lower frequency of adverse reactions. Therapy with umifenovir, led to an increase percentage of patients with negative results of PCR tests on days 714 (I2=69.8%, RR 0.48, 95% CI 0.190.76; p=0.001). The efficacy and safety of antivirals against SARS-CoV-2 still requires clinical investigation. Moderate forms of COVID-19 could be effectively treated by antivirals, but severe forms of COVID-19, characterized by pulmonary immunopathology, require different approaches to treatment.

scholarly journals For an Application of Protease Inhibitor for the Treatment of Viral Respiratory Infections - Acceptable Concentrations of a Protease Inhibitor Nafamostat and Ammonium Chloride for Direct Administration to the Respiratory Epithelium of Mice

2021 ◽  
Author(s):  
Satoko Nakagomi
Keyword(s):  
Adverse Effects ◽  
Protease Inhibitor ◽  
Viral Infection ◽  
Viral Entry ◽  
Respiratory Infections ◽  
Inbred Mice ◽  
Respiratory Epithelium ◽  
Viral Respiratory Infections ◽  
Viral Respiratory

Abstract Many enveloped respiratory viruses, including SARS-CoV-2, require host proteases for the infection, and in-vitro studies have demonstrated that protease inhibitors suppress viral infection. However, no application of inhibitors for the treatment of viral respiratory infections have been reported. This is because no method has been established to efficiently deliver inhibitors to the respiratory epithelium. This study explores methods to safely deliver a protease inhibitor nafamostat by assessing whether adverse effects occur when nafamostat is administered directly to the respiratory epithelium.To observe the effect of direct respiratory administration on organisms, inbred mice were intranasally administered the inhibitor solutions under anesthesia. 200µM nafamostat at 20µL/day for 1 week could be administered without any adverse effects. Since 1µM nafamostat is known to suppress the viral entry to cell in vitro, 200µM nafamostat is expected to show enough inhibitory effect also in mice.Ammonium chloride (NH4Cl) is also known to block the viral entry via endosome. The present study has demonstrated that 74mM NH4Cl could be also administered in the same manner. Since the NH4Cl solution at 50mM is known to efficiently suppress the entry of SARS-CoV-2 via endosome in vitro, NH4Cl may be also available to treat viral infection in vivo.Results of the present study encourage the research to apply nafamostat and also NH4Cl for the treatment of respiratory viral infection, including COVID-19.

scholarly journals Combination of CCR5 and CXCR4 Inhibitors in Therapy of Human Immunodeficiency Virus Type 1 Infection: In Vitro Studies of Mixed Virus Infections

2000 ◽  
Vol 74 (19) ◽  
pp. 9328-9332 ◽  
Author(s):  
Stefano Rusconi ◽  
Simona La Seta Catamancio ◽  
Paola Citterio ◽  
Elisabetta Bulgheroni ◽  
Francesco Croce ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Opposite Effect ◽  
Antiviral Agents ◽  
Virus Infections ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT We studied the combined anti-human immunodeficiency virus type 1 (HIV-1) effects of a derivative of stroma-derived factor 1β (SDF-1β), Met-SDF-1β, and a modified form of RANTES, aminooxypentane (AOP)-RANTES. The antiviral agents were tested singly or in combination at 95 and 99% virus inhibitory concentrations. Clinical R5 and X4 HIV-1 isolates were used. AOP-RANTES inhibited R5 but not X4 viruses, whereas Met-SDF-1β had the opposite effect. Combinations of these compounds inhibited mixed infections with R5 and X4 viruses (95 to 99%), whereas single drugs were less inhibitory (32 to 61%). Combinations of R5 and X4 inhibitors are promising and deserve further evaluation.

scholarly journals Translational Modeling of Chloroquine and Hydroxychloroquine Dosimetry in Human Airways for Treating Viral Respiratory Infections

2022 ◽  
Author(s):  
Aditya R. Kolli ◽  
Florian Calvino-Martin ◽  
Julia Hoeng
Keyword(s):  
Respiratory Tract ◽  
Cell Lines ◽  
Respiratory Infections ◽  
Systemic Exposure ◽  
Human Airway ◽  
Dosing Regimens ◽  
Viral Respiratory Infections ◽  
Viral Respiratory

Abstract Purpose Chloroquine and hydroxychloroquine are effective against respiratory viruses in vitro. However, they lack antiviral efficacy upon oral administration. Translation of in vitro to in vivo exposure is necessary for understanding the disconnect between the two to develop effective therapeutic strategies. Methods We employed an in vitro ion-trapping kinetic model to predict the changes in the cytosolic and lysosomal concentrations of chloroquine and hydroxychloroquine in cell lines and primary human airway cultures. A physiologically based pharmacokinetic model with detailed respiratory physiology was used to predict regional airway exposure and optimize dosing regimens. Results At their reported in vitro effective concentrations in cell lines, chloroquine and hydroxychloroquine cause a significant increase in their cytosolic and lysosomal concentrations by altering the lysosomal pH. Higher concentrations of the compounds are required to achieve similar levels of cytosolic and lysosomal changes in primary human airway cells in vitro. The predicted cellular and lysosomal concentrations in the respiratory tract for in vivo oral doses are lower than the in vitro effective levels. Pulmonary administration of aerosolized chloroquine or hydroxychloroquine is predicted to achieve high bound in vitro-effective concentrations in the respiratory tract, with low systemic exposure. Achieving effective cytosolic concentrations for activating immunomodulatory effects and adequate lysosomal levels for inhibiting viral replication could be key drivers for treating viral respiratory infections. Conclusion Our analysis provides a framework for extrapolating in vitro effective concentrations of chloroquine and hydroxychloroquine to in vivo dosing regimens for treating viral respiratory infections. Graphical abstract

Sign in / Sign up

Export Citation Format

Share Document