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Article ; Online: Broad-Spectrum Antivirals and Antiviral Drug Combinations.

Oksenych, Valentyn / Kainov, Denis E

2022 Volume 14, Issue 2

Abstract: Viral diseases consistently pose a substantial economic and public health burden worldwide [ ... ]. ...

Abstract	Viral diseases consistently pose a substantial economic and public health burden worldwide [...].
MeSH term(s)	Antiviral Agents/pharmacology ; Humans ; Virus Diseases/drug therapy ; Virus Diseases/virology ; Virus Physiological Phenomena ; Viruses/classification ; Viruses/drug effects ; Viruses/genetics
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2022-02-01
Publishing country	Switzerland
Document type	Editorial ; Introductory Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14020301
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: DNA Damage Response.

Oksenych, Valentyn / Kainov, Denis E

Biomolecules

2021 Volume 11, Issue 1

Abstract: DNA in our cells is constantly modified by internal and external factors [ ... ]. ...

Abstract	DNA in our cells is constantly modified by internal and external factors [...].
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; DNA Damage ; DNA Repair/genetics ; Disease Models, Animal ; Epistasis, Genetic/drug effects ; Humans ; Mice
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2021-01-19
Publishing country	Switzerland
Document type	Editorial ; Introductory Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom11010123
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Novel Synergistic Anti-Enteroviral Drug Combinations

Ianevski, Aleksandr / Zusinaite, Eva / Tenson, Tanel / Oksenych, Valentyn / Wang, Wei / Afset, Jan Egil / Bjørås, Magnar / Kainov, Denis E.

Viruses. 2022 Aug. 25, v. 14, no. 9

2022

Abstract: 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 treatments for enterovirus infections. Methods: We have tested our library of ...

Abstract	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 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 cocktails may have fewer side effects in vivo and, therefore, should be further explored in preclinical and clinical trials against EV1 and other enterovirus infections.
Keywords	Enterovirus ; adenocarcinoma ; cycloheximide ; emetine ; epithelium ; humans
Language	English
Dates of publication	2022-0825
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v14091866
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Seven classes of antiviral agents

Ianevski, Aleksandr / Ahmad, Shahzaib / Anunnitipat, Kraipit / Oksenych, Valentyn / Zusinaite, Eva / Tenson, Tanel / Bjørås, Magnar / Kainov, Denis E.

Cell. Mol. Life Sci.. 2022 Dec., v. 79, no. 12 p.605-605

2022

Abstract: The viral epidemics and pandemics have stimulated the development of known and the discovery of novel antiviral agents. About a hundred mono- and combination antiviral drugs have been already approved, whereas thousands are in development. Here, we ... ...

Abstract	The viral epidemics and pandemics have stimulated the development of known and the discovery of novel antiviral agents. About a hundred mono- and combination antiviral drugs have been already approved, whereas thousands are in development. Here, we briefly reviewed 7 classes of antiviral agents: neutralizing antibodies, neutralizing recombinant soluble human receptors, antiviral CRISPR/Cas systems, interferons, antiviral peptides, antiviral nucleic acid polymers, and antiviral small molecules. Interferons and some small molecules alone or in combinations possess broad-spectrum antiviral activity, which could be beneficial for treatment of emerging and re-emerging viral infections.
Keywords	antiviral properties ; humans ; nucleic acids ; peptides
Language	English
Dates of publication	2022-12
Size	p. 605.
Publishing place	Springer International Publishing
Document type	Article ; Online
Note	Review
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-022-04635-1
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Novel Synergistic Anti-Enteroviral Drug Combinations.

Ianevski, Aleksandr / Zusinaite, Eva / Tenson, Tanel / Oksenych, Valentyn / Wang, Wei / Afset, Jan Egil / Bjørås, Magnar / Kainov, Denis E

Viruses

2022 Volume 14, Issue 9

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Anisomycin/therapeutic use ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Cycloheximide/therapeutic use ; Drug Combinations ; Emetine ; Enterovirus Infections ; Humans ; Picornaviridae ; Vemurafenib/therapeutic use
Chemical Substances	Antiviral Agents ; Drug Combinations ; Vemurafenib (207SMY3FQT) ; Anisomycin (6C74YM2NGI) ; Cycloheximide (98600C0908) ; Emetine (X8D5EPO80M)
Language	English
Publishing date	2022-08-25
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14091866
Database	MEDical Literature Analysis and Retrieval System OnLINE

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

Ianevski, Aleksandr / Simonsen, Ronja M / Myhre, Vegard / Tenson, Tanel / Oksenych, Valentyn / Bjørås, Magnar / Kainov, Denis E

Nucleic acids research

2022 Volume 50, Issue W1, Page(s) W272–W275

Abstract: 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) ... ...

Abstract	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.
MeSH term(s)	Humans ; Antiviral Agents/pharmacology ; Drug Combinations ; Drug Development ; Viruses/drug effects ; Databases, Pharmaceutical ; Software ; Internet
Chemical Substances	Antiviral Agents ; Drug Combinations
Language	English
Publishing date	2022-05-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkac348
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Article ; Online: Seven classes of antiviral agents.

Ianevski, Aleksandr / Ahmad, Shahzaib / Anunnitipat, Kraipit / Oksenych, Valentyn / Zusinaite, Eva / Tenson, Tanel / Bjørås, Magnar / Kainov, Denis E

Cellular and molecular life sciences : CMLS

2022 Volume 79, Issue 12, Page(s) 605

Abstract	The viral epidemics and pandemics have stimulated the development of known and the discovery of novel antiviral agents. About a hundred mono- and combination antiviral drugs have been already approved, whereas thousands are in development. Here, we briefly reviewed 7 classes of antiviral agents: neutralizing antibodies, neutralizing recombinant soluble human receptors, antiviral CRISPR/Cas systems, interferons, antiviral peptides, antiviral nucleic acid polymers, and antiviral small molecules. Interferons and some small molecules alone or in combinations possess broad-spectrum antiviral activity, which could be beneficial for treatment of emerging and re-emerging viral infections.
MeSH term(s)	Humans ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Antiviral Agents/chemistry ; Interferons ; Virus Diseases/drug therapy
Chemical Substances	Antiviral Agents ; Interferons (9008-11-1)
Language	English
Publishing date	2022-11-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-022-04635-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 195: Show issues

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Article ; Online: The combination of pleconaril, rupintrivir, and remdesivir efficiently inhibits enterovirus infections in vitro, delaying the development of drug-resistant virus variants.

Ianevski, Aleksandr / Frøysa, Irene Trøen / Lysvand, Hilde / Calitz, Carlemi / Smura, Teemu / Schjelderup Nilsen, Hans-Johnny / Høyer, Erling / Afset, Jan Egil / Sridhar, Adithya / Wolthers, Katja C / Zusinaite, Eva / Tenson, Tanel / Kurg, Reet / Oksenych, Valentyn / Galabov, Angel S / Stoyanova, Adelina / Bjørås, Magnar / Kainov, Denis E

Antiviral research

2024 Volume 224, Page(s) 105842

Abstract: Enteroviruses are a significant global health concern, causing a spectrum of diseases from the common cold to more severe conditions like hand-foot-and-mouth disease, meningitis, myocarditis, pancreatitis, and poliomyelitis. Current treatment options for ...

Abstract	Enteroviruses are a significant global health concern, causing a spectrum of diseases from the common cold to more severe conditions like hand-foot-and-mouth disease, meningitis, myocarditis, pancreatitis, and poliomyelitis. Current treatment options for these infections are limited, underscoring the urgent need for effective therapeutic strategies. To find better treatment option we analyzed toxicity and efficacy of 12 known broad-spectrum anti-enterovirals both individually and in combinations against different enteroviruses in vitro. We identified several novel, synergistic two-drug and three-drug combinations that demonstrated significant inhibition of enterovirus infections in vitro. Specifically, the triple-drug combination of pleconaril, rupintrivir, and remdesivir exhibited remarkable efficacy against echovirus (EV) 1, EV6, EV11, and coxsackievirus (CV) B5, in human lung epithelial A549 cells. This combination surpassed the effectiveness of single-agent or dual-drug treatments, as evidenced by its ability to protect A549 cells from EV1-induced cytotoxicity across seven passages. Additionally, this triple-drug cocktail showed potent antiviral activity against EV-A71 in human intestinal organoids. Thus, our findings highlight the therapeutic potential of the pleconaril-rupintrivir-remdesivir combination as a broad-spectrum treatment option against a range of enterovirus infections. The study also paves the way towards development of strategic antiviral drug combinations with virus family coverage and high-resistance barriers.
MeSH term(s)	Animals ; Humans ; Enterovirus A, Human ; Enterovirus ; Enterovirus Infections/drug therapy ; Enterovirus B, Human ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Drug Combinations ; Adenosine Monophosphate/analogs & derivatives ; Oxadiazoles ; Pyrrolidinones ; Oxazoles ; Valine/analogs & derivatives ; Isoxazoles ; Phenylalanine/analogs & derivatives ; Alanine/analogs & derivatives
Chemical Substances	pleconaril (9H4570Q89D) ; rupintrivir (RGE5K1Q5QW) ; remdesivir (3QKI37EEHE) ; Antiviral Agents ; Drug Combinations ; Adenosine Monophosphate (415SHH325A) ; Oxadiazoles ; Pyrrolidinones ; Oxazoles ; Valine (HG18B9YRS7) ; Isoxazoles ; Phenylalanine (47E5O17Y3R) ; Alanine (OF5P57N2ZX)
Language	English
Publishing date	2024-02-26
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	306628-9
ISSN	1872-9096 ; 0166-3542
ISSN (online)	1872-9096
ISSN	0166-3542
DOI	10.1016/j.antiviral.2024.105842
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 1627: Show issues

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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Combating pan-coronavirus infection by indomethacin through simultaneously inhibiting viral replication and inflammatory response.

Wang, Yining / Li, Pengfei / Xu, Lei / de Vries, Annemarie C / Rottier, Robbert J / Wang, Wenshi / Crombag, Marie-Rose B S / Peppelenbosch, Maikel P / Kainov, Denis E / Pan, Qiuwei

iScience

2023 Volume 26, Issue 9, Page(s) 107631

Abstract: Severe infections with coronaviruses are often accompanied with hyperinflammation, requiring therapeutic strategies to simultaneously tackle the virus and inflammation. By screening a safe-in-human broad-spectrum antiviral agents library, we identified ... ...

Abstract	Severe infections with coronaviruses are often accompanied with hyperinflammation, requiring therapeutic strategies to simultaneously tackle the virus and inflammation. By screening a safe-in-human broad-spectrum antiviral agents library, we identified that indomethacin can inhibit pan-coronavirus infection in human cell and airway organoids models. Combining indomethacin with oral antiviral drugs authorized for treating COVID-19 results in synergistic anti-coronavirus activity. Coincidentally, screening a library of FDA-approved drugs identified indomethacin as the most potent potentiator of interferon response through increasing STAT1 phosphorylation. Combining indomethacin with interferon-alpha exerted synergistic antiviral effects against multiple coronaviruses. The anti-coronavirus activity of indomethacin is associated with activating interferon response. In a co-culture system of lung epithelial cells with macrophages, indomethacin inhibited both viral replication and inflammatory response. Collectively, indomethacin is a pan-coronavirus inhibitor that can simultaneously inhibit virus-triggered inflammatory response. The therapeutic potential of indomethacin can be further augmented by combining it with oral antiviral drugs or interferon-alpha.
Language	English
Publishing date	2023-08-16
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.107631
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Nafamostat–Interferon-α Combination Suppresses SARS-CoV-2 Infection In Vitro and In Vivo by Cooperatively Targeting Host TMPRSS2

Ianevski, Aleksandr / Yao, Rouan / Lysvand, Hilde / Grødeland, Gunnveig / Legrand, Nicolas / Oksenych, Valentyn / Zusinaite, Eva / Tenson, Tanel / Bjørås, Magnar / Kainov, Denis E.

Viruses. 2021 Sept. 04, v. 13, no. 9

2021

Abstract: SARS-CoV-2 and its vaccine/immune-escaping variants continue to pose a serious threat to public health due to a paucity of effective, rapidly deployable, and widely available treatments. Here, we address these challenges by combining Pegasys (IFNα) and ... ...

Abstract	SARS-CoV-2 and its vaccine/immune-escaping variants continue to pose a serious threat to public health due to a paucity of effective, rapidly deployable, and widely available treatments. Here, we address these challenges by combining Pegasys (IFNα) and nafamostat to effectively suppress SARS-CoV-2 infection in cell culture and hamsters. Our results indicate that Serpin E1 is an important mediator of the antiviral activity of IFNα and that both Serpin E1 and nafamostat can target the same cellular factor TMPRSS2, which plays a critical role in viral replication. The low doses of the drugs in combination may have several clinical advantages, including fewer adverse events and improved patient outcome. Thus, our study may provide a proactive solution for the ongoing pandemic and potential future coronavirus outbreaks, which is still urgently required in many parts of the world.
Keywords	Severe acute respiratory syndrome coronavirus 2 ; antiviral properties ; cell culture ; pandemic ; patients ; plasminogen activator inhibitors ; public health ; virus replication
Language	English
Dates of publication	2021-0904
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v13091768
Database	NAL-Catalogue (AGRICOLA)

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