A Systems Approach to Study Immuno- and Neuro-Modulatory Properties of Antiviral Agents

Žusinaite, Eva; Ianevski, Aleksandr; Niukkanen, Diana; Poranen, Minna M.; Bjørås, Magnar; Afset, Jan Egil; Tenson, Tanel; Velagapudi, Vidya; Merits, Andres; Kainov, Denis E.

doi:10.3390/v10080423

Cited by 11 publications

(8 citation statements)

References 58 publications

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“…IFNα induces transcription of IFIT1, IFIT2, and IFIT3, as well as of OASL and OAS2, which recognize viral RNA and catalyze RNase L-mediated RNA degradation, respectively. Remdesivir, EIDD-2801, NITD008, ribavirin, sofosbuvir, pimodivir, and lamivudine, also inhibit viral RNA transcription [53,54,60,64]. Therefore, these antiviral agents and IFNα target the same step of viral replication to achieve synergy.…”

Section: Discussionmentioning

confidence: 99%

Synergistic Interferon-Alpha-Based Combinations for Treatment of SARS-CoV-2 and Other Viral Infections

Ianevski

Yao

Žusinaite

et al. 2021

Viruses

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Background: There is an urgent need for new antivirals with powerful therapeutic potential and tolerable side effects. Methods: Here, we tested the antiviral properties of interferons (IFNs), alone and with other drugs in vitro. Results: While IFNs alone were insufficient to completely abolish replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), IFNα, in combination with remdesivir, EIDD-2801, camostat, cycloheximide, or convalescent serum, proved to be more effective. Transcriptome and metabolomic analyses revealed that the IFNα–remdesivir combination suppressed SARS-CoV-2-mediated changes in Calu-3 cells and lung organoids, although it altered the homeostasis of uninfected cells and organoids. We also demonstrated that IFNα combinations with sofosbuvir, telaprevir, NITD008, ribavirin, pimodivir, or lamivudine were effective against HCV, HEV, FLuAV, or HIV at lower concentrations, compared to monotherapies. Conclusions: Altogether, our results indicated that IFNα can be combined with drugs that affect viral RNA transcription, protein synthesis, and processing to make synergistic combinations that can be attractive targets for further pre-clinical and clinical development against emerging and re-emerging viral infections.

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Section: Discussionmentioning

confidence: 99%

Synergistic Interferon-Alpha-Based Combinations for Treatment of SARS-CoV-2 and Other Viral Infections

Ianevski

Yao

Žusinaite

et al. 2021

Viruses

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“…Many of these drugs have side effects which can only be revealed in clinical studies or long-term post-market monitoring and can be challenging and time-consuming to identify. Here, we used in silico and in vitro approaches [ 24 ] to study the effects of 45 commonly prescribed medicines on FLUAV–host cell interaction. By simultaneously leveraging drug–target interaction studies, drug toxicity/efficacy tests, transcriptomics, and metabolomics, we were able to observe drug-induced transcriptional and metabolomic changes in the context of both FLUAV and mock infection.…”

Section: Discussionmentioning

confidence: 99%

Active Components of Commonly Prescribed Medicines Affect Influenza A Virus–Host Cell Interaction: A Pilot Study

Ianevski

Yao

Žusinaite

et al. 2021

Viruses

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Background: Every year, millions of people are hospitalized and thousands die from influenza A virus (FLUAV) infection. Most cases of hospitalizations and death occur among the elderly. Many of these elderly patients are reliant on medical treatment of underlying chronic diseases, such as arthritis, diabetes, and hypertension. We hypothesized that the commonly prescribed medicines for treatment of underlying chronic diseases can affect host responses to FLUAV infection and thus contribute to the morbidity and mortality associated with influenza. Therefore, the aim of this study was to examine whether commonly prescribed medicines could affect host responses to virus infection in vitro. Methods: We first identified 45 active compounds from a list of commonly prescribed medicines. Then, we constructed a drug–target interaction network and identified the potential implication of these interactions for FLUAV–host cell interplay. Finally, we tested the effect of 45 drugs on the viability, transcription, and metabolism of mock- and FLUAV-infected human retinal pigment epithelial (RPE) cells. Results: In silico drug–target interaction analysis revealed that drugs such as atorvastatin, candesartan, and hydroxocobalamin could target and modulate FLUAV–host cell interaction. In vitro experiments showed that at non-cytotoxic concentrations, these compounds affected the transcription and metabolism of FLUAV- and mock-infected cells. Conclusion: Many commonly prescribed drugs were found to modulate FLUAV–host cell interactions in silico and in vitro and could therefore affect their interplay in vivo, thus contributing to the morbidity and mortality of patients with influenza virus infections.

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“…To date, 86 different drugs have been approved for the treatment of 17 viral infections [67]. However, some drugs have serious side effects, including nausea, insomnia, vomiting, allergic reactions, behavior disorders, cardiovascular complications, and dependency [68]. Opening new therapeutic windows, decreasing the side effects while maintaining their efficacy, is a key action.…”

Section: The Role Of Dendritic Materials Against Viral Infectionsmentioning

confidence: 99%

Dendrimers and Dendritic Materials: From Laboratory to Medical Practice in Infectious Diseases

et al. 2020

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Infectious diseases are one of the main global public health risks, predominantly caused by viruses, bacteria, fungi, and parasites. The control of infections is founded on three main pillars: prevention, treatment, and diagnosis. However, the appearance of microbial resistance has challenged traditional strategies and demands new approaches. Dendrimers are a type of polymeric nanoparticles whose nanometric size, multivalency, biocompatibility, and structural perfection offer boundless possibilities in multiple biomedical applications. This review provides the reader a general overview about the uses of dendrimers and dendritic materials in the treatment, prevention, and diagnosis of highly prevalent infectious diseases, and their advantages compared to traditional approaches. Examples of dendrimers as antimicrobial agents per se, as nanocarriers of antimicrobial drugs, as well as their uses in gene transfection, in vaccines or as contrast agents in imaging assays are presented. Despite the need to address some challenges in order to be used in the clinic, dendritic materials appear as an innovative tool with a brilliant future ahead in the clinical management of infectious diseases and many other health issues.

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A Systems Approach to Study Immuno- and Neuro-Modulatory Properties of Antiviral Agents

Cited by 11 publications

References 58 publications

Synergistic Interferon-Alpha-Based Combinations for Treatment of SARS-CoV-2 and Other Viral Infections

Synergistic Interferon-Alpha-Based Combinations for Treatment of SARS-CoV-2 and Other Viral Infections

Active Components of Commonly Prescribed Medicines Affect Influenza A Virus–Host Cell Interaction: A Pilot Study

Dendrimers and Dendritic Materials: From Laboratory to Medical Practice in Infectious Diseases

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