Mono- and combinational drug therapies for global viral pandemic preparedness

Ianevski, Aleksandr; Yao, Rouan; Simonsen, Ronja M.; Myhre, Vegard; Ravlo, Erlend; Kaynova, Gerda Dominyka; Žusinaite, Eva; White, Judith M.; Polyak, Stephen J.; Oksenych, Valentyn; Windisch, Marc P.; Pan, Qiuwei; Lastauskienė, Eglė; Vitkauskienė, Astra; Matukevičius, Algimantas; Tenson, Tanel; Bjørås, Magnar; Kainov, Denis E.

doi:10.1016/j.isci.2022.104112

Cited by 27 publications

(33 citation statements)

References 79 publications

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“…We showed that synergistic combinations of the virus-directed rupintrivir and pleconaril require lower concentration of drugs than monotherapies to inhibit EV1 replication in vitro and thus could have fewer side effects in vivo. We also confirmed our previous hypothesis that combination of virus-directed drugs could have more benefits than combinations of virus-and host-, or only host-directed antivirals [7].…”

Section: Discussionsupporting

confidence: 90%

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Novel Synergistic Anti-Enteroviral Drug Combinations

Ianevski¹,

Žusinaite²,

Tenson³

et al. 2022

Preprint

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Background: Enterovirus infections affect people around the world, causing a range of illnesses, from mild fevers to severe, potentially fatal conditions. There are no approved vaccines or treatments for enterovirus infections. Methods: We have tested our library of broad-spectrum antiviral agents (BSAs) against echovirus 1 (EV1) in human adenocarcinoma alveolar basal epithelial A549 cells. We also tested combinations of the most active compounds against EV1 in A549 and human immortalized retinal pigment epithelium RPE cells. Results: We confirmed anti-enteroviral activities of pleconaril, rupintrivir, cycloheximide, vemurafenib, remdesivir, emetine, and anisomycin and identified novel synergistic rupintrivir-vemurafenib, vemurafenib-pleconaril and rupintrivir-pleconaril combinations against EV1 infection. Conclusions: Because rupintrivir, vemurafenib, and pleconaril require lower concentrations to inhibit enterovirus replication in vitro when combined, their combinations may have fewer side effects in vivo and therefore should be further studied in pre- and clinical trials.

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Section: Discussionsupporting

confidence: 90%

“…Previously, our group has extensively reviewed and identified >250 approved, investigational, and experimental BSAs [7,9]. We made a database to summarize information on the BSAs (https://drugvirus.info/).…”

Section: Resultsmentioning

confidence: 99%

Novel Synergistic Anti-Enteroviral Drug Combinations

Ianevski¹,

Žusinaite²,

Tenson³

et al. 2022

Preprint

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“…To date, there are hundreds of known BSAs and BCCs, and the landscape of BSA and BCC activities and virus coverage will be further interrogated and expanded ( 3 , 4 ). However, new solutions are urgently needed to identify the most promising hits out of thousands of potential BSAs and BCCs to prioritize their development during the critical period between the emergence of new viruses and the development of virus-specific vaccines, drugs, and therapeutic antibodies ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

DrugVirus.info 2.0: an integrative data portal for broad-spectrum antivirals (BSA) and BSA-containing drug combinations (BCCs)

Ianevski

Simonsen

Myhre

et al. 2022

Nucleic Acids Research

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Viruses can cross species barriers and cause unpredictable outbreaks in man with substantial economic and public health burdens. Broad-spectrum antivirals, (BSAs, compounds inhibiting several human viruses), and BSA-containing drug combinations (BCCs) are deemed as immediate therapeutic options that fill the void between virus identification and vaccine development. Here, we present DrugVirus.info 2.0 (https://drugvirus.info), an integrative interactive portal for exploration and analysis of BSAs and BCCs, that greatly expands the database and functionality of DrugVirus.info 1.0 webserver. Through the data portal that now expands the spectrum of BSAs and provides information on BCCs, we developed two modules for (i) interactive analysis of users’ own antiviral drug and combination screening data and their comparison with published datasets, and (ii) exploration of the structure–activity relationship between various BSAs. The updated portal provides an essential toolbox for antiviral drug development and repurposing applications aiming to identify existing and novel treatments of emerging and re-emerging viral threats.

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“…This burden is due to the ability of viruses to be transmitted from wild and domestic animals to humans, resulting in unpredictable outbreaks. The current strategy for the viral outbreak management is heavily reliant on vaccines and antiviral treatments [1]. While the development of novel vaccines and monoclonal neutralizing antibodies is often long, laborious, and unprofitable, polyclonal neutralizing antibodies remain effective disease management option [2].…”

Section: Introductionmentioning

confidence: 99%

Norwegian Platform for Production of Antiviral Chicken Egg Yolk Immunoglobulins for Viral Pandemics Preparedness

Evensen¹,

Sanson²,

Ianevski³

et al. 2022

Preprint

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Background: Some viruses cause outbreaks which require immediate attention. Neutralizing antibodies could be developed for viral outbreak management. However, development of monoclonal antibodies is often long, laborious, and unprofitable. Here we report a Norwegian platform for development of chicken polyclonal neutralizing antibodies with powerful therapeutic potential. Methods: Layers were immunized twice with 14-day interval using purified RBD of SARS-CoV-2. Eggs were harvested 14 days after the second immunization. Polyclonal IgY antibodies were extracted. Binding of anti-RBD IgY to RBD was measured by indirect ELISA. Neutralization capacity of anti-RBD IgYs was measured in Vero-E6 cells infected with SARS-CoV-2-mCherry strain using fluorescence and cell viability assay. In addition, the effect of IgYs on the expression of SARS-CoV-2 and host cytokine genes in lungs of Syrian Golden hamsters was examined using qRT-PCR. Results: Anti-RBD IgYs efficiently bind RBD of S protein of SARS-CoV-2 in situ, neutralize the virus in vitro, and lower viral RNA amplification without significant alteration of virus-mediated immune gene expression in vivo. Conclusions: Altogether, our results indicated that chicken polyclonal IgYs can be attractive targets for pre-clinical and clinical development for rapid management of outbreaks of emerging and re-emerging viruses.

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Mono- and combinational drug therapies for global viral pandemic preparedness

Cited by 27 publications

References 79 publications

Novel Synergistic Anti-Enteroviral Drug Combinations

Novel Synergistic Anti-Enteroviral Drug Combinations

DrugVirus.info 2.0: an integrative data portal for broad-spectrum antivirals (BSA) and BSA-containing drug combinations (BCCs)

Norwegian Platform for Production of Antiviral Chicken Egg Yolk Immunoglobulins for Viral Pandemics Preparedness

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