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Viruses
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Antiviral Drug Combinations
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Antiviral Drug Combinations

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (31 August 2020) | Viewed by 28891

Special Issue Editor

Prof. Dr. Denis E. Kainov

E-Mail Website
Guest Editor
Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, 7028 Trondheim, Norway
Interests: antiviral agents; broad-spectrum antivirals; antiviral response; innate immunity; adaptive immunity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Viral diseases are the leading cause of morbidity and mortality in developing countries. Antiviral agents are key players in the control of viral diseases. Antiviral agents could be combined to obtain synergistic or additive effects against certain viruses. Combination therapies became a standard for the treatment of HIV and HCV infections. These include abacavir/dolutegravir/lamivudine (Triumeq), darunavir/cobicistat/emtricitabine/tenofovir (Symtuza), lopinavir/ritonavir (Kaletra), ledipasvir/sofosbuvir, and sofosbuvir/velpatasvir. Drug combinations could also be used to target several viral infections or co/infections. Such combinations could serve as frontline therapeutics against poorly characterized emerging viruses or re-emerging drug-resistant viral strains. We thus invite submission of original research manuscripts and review articles that cover any aspects of antiviral drug combinations and related topics.

I look forward for your contribution.

Prof. Dr. Denis E. Kainov
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Antiviral agents
  • Antiviral drug combinations
  • Broad-spectrum antivirals
  • Antiviral response
  • Innate immunity
  • Adaptive immunity

Published Papers (4 papers)

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Research

15 pages, 3468 KiB  
Article
Identification and Tracking of Antiviral Drug Combinations
by Aleksandr Ianevski, Rouan Yao, Svetlana Biza, Eva Zusinaite, Andres Mannik, Gaily Kivi, Anu Planken, Kristiina Kurg, Eva-Maria Tombak, Mart Ustav, Jr., Nastassia Shtaida, Evgeny Kulesskiy, Eunji Jo, Jaewon Yang, Hilde Lysvand, Kirsti Løseth, Valentyn Oksenych, Per Arne Aas, Tanel Tenson, Astra Vitkauskienė, Marc P. Windisch, Mona Høysæter Fenstad, Svein Arne Nordbø, Mart Ustav, Magnar Bjørås and Denis E. Kainovadd Show full author list remove Hide full author list
Viruses 2020, 12(10), 1178; https://0-doi-org.brum.beds.ac.uk/10.3390/v12101178 - 18 Oct 2020
Cited by 42 | Viewed by 6308
Abstract
Combination therapies have become a standard for the treatment for HIV and hepatitis C virus (HCV) infections. They are advantageous over monotherapies due to better efficacy, reduced toxicity, as well as the ability to prevent the development of resistant viral strains and to [...] Read more.
Combination therapies have become a standard for the treatment for HIV and hepatitis C virus (HCV) infections. They are advantageous over monotherapies due to better efficacy, reduced toxicity, as well as the ability to prevent the development of resistant viral strains and to treat viral co-infections. Here, we identify new synergistic combinations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), echovirus 1 (EV1), hepatitis C virus (HCV) and human immunodeficiency virus 1 (HIV-1) in vitro. We observed synergistic activity of nelfinavir with convalescent serum and with purified neutralizing antibody 23G7 against SARS-CoV-2 in human lung epithelial Calu-3 cells. We also demonstrated synergistic activity of nelfinavir with EIDD-2801 or remdesivir in Calu-3 cells. In addition, we showed synergistic activity of vemurafenib with emetine, homoharringtonine, anisomycin, or cycloheximide against EV1 infection in human lung epithelial A549 cells. We also found that combinations of sofosbuvir with brequinar or niclosamide are synergistic against HCV infection in hepatocyte-derived Huh-7.5 cells, and that combinations of monensin with lamivudine or tenofovir are synergistic against HIV-1 infection in human cervical TZM-bl cells. These results indicate that synergy is achieved when a virus-directed antiviral is combined with another virus- or host-directed agent. Finally, we present an online resource that summarizes novel and known antiviral drug combinations and their developmental status. Full article
(This article belongs to the Special Issue Antiviral Drug Combinations)
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12 pages, 1360 KiB  
Article
In Vitro Combinations of Baloxavir Acid and Other Inhibitors against Seasonal Influenza A Viruses
by Liva Checkmahomed, Blandine Padey, Andrés Pizzorno, Olivier Terrier, Manuel Rosa-Calatrava, Yacine Abed, Mariana Baz and Guy Boivin
Viruses 2020, 12(10), 1139; https://0-doi-org.brum.beds.ac.uk/10.3390/v12101139 - 08 Oct 2020
Cited by 15 | Viewed by 2670
Abstract
Two antiviral classes, the neuraminidase inhibitors (NAIs) and polymerase inhibitors (baloxavir marboxil and favipiravir) can be used to prevent and treat influenza infections during seasonal epidemics and pandemics. However, prolonged treatment may lead to the emergence of drug resistance. Therapeutic combinations constitute an [...] Read more.
Two antiviral classes, the neuraminidase inhibitors (NAIs) and polymerase inhibitors (baloxavir marboxil and favipiravir) can be used to prevent and treat influenza infections during seasonal epidemics and pandemics. However, prolonged treatment may lead to the emergence of drug resistance. Therapeutic combinations constitute an alternative to prevent resistance and reduce antiviral doses. Therefore, we evaluated in vitro combinations of baloxavir acid (BXA) and other approved drugs against influenza A(H1N1)pdm09 and A(H3N2) subtypes. The determination of an effective concentration inhibiting virus cytopathic effects by 50% (EC50) for each drug and combination indexes (CIs) were based on cell viability. CompuSyn software was used to determine synergism, additivity or antagonism between drugs. Combinations of BXA and NAIs or favipiravir had synergistic effects on cell viability against the two influenza A subtypes. Those effects were confirmed using a physiological and predictive ex vivo reconstructed human airway epithelium model. On the other hand, the combination of BXA and ribavirin showed mixed results. Overall, BXA stands as a good candidate for combination with several existing drugs, notably oseltamivir and favipiravir, to improve in vitro antiviral activity. These results should be considered for further animal and clinical evaluations. Full article
(This article belongs to the Special Issue Antiviral Drug Combinations)
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15 pages, 4236 KiB  
Article
Combinatory Treatment with Oseltamivir and Itraconazole Targeting Both Virus and Host Factors in Influenza A Virus Infection
by Sebastian Schloer, Jonas Goretzko, Stephan Pleschka, Stephan Ludwig and Ursula Rescher
Viruses 2020, 12(7), 703; https://0-doi-org.brum.beds.ac.uk/10.3390/v12070703 - 29 Jun 2020
Cited by 17 | Viewed by 3268
Abstract
Influenza virus infections and their associated morbidity and mortality are a major threat to global health. Vaccination is an effective influenza prevention measure; however, the effectiveness is challenged by the rapid changes in the influenza virus genome leading to viral adaptation. Emerging viral [...] Read more.
Influenza virus infections and their associated morbidity and mortality are a major threat to global health. Vaccination is an effective influenza prevention measure; however, the effectiveness is challenged by the rapid changes in the influenza virus genome leading to viral adaptation. Emerging viral resistance to the neuraminidase inhibitor oseltamivir limits the treatment of acute influenza infections. Targeting influenza virus-host interactions is a new and emerging field, and therapies based on the combination of virus- and host-directed drugs might significantly improve treatment success. We therefore assessed the combined treatment with oseltamivir and the repurposed antifungal drug itraconazole on infection of polarized broncho-epithelial Calu-3 cells with pdm09 or Panama influenza A virus strains. We detected significantly stronger antiviral activities in the combined treatment compared to monotherapy with oseltamivir, permitting lower concentrations of the drug than required for the single treatments. Bliss independence drug interaction analysis indicated that both drugs acted independently of each other. The additional antiviral effect of itraconazole might safeguard patients infected with influenza virus strains with heightened oseltamivir resistance. Full article
(This article belongs to the Special Issue Antiviral Drug Combinations)
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19 pages, 2735 KiB  
Article
Potential Antiviral Options against SARS-CoV-2 Infection
by Aleksandr Ianevski, Rouan Yao, Mona Høysæter Fenstad, Svetlana Biza, Eva Zusinaite, Tuuli Reisberg, Hilde Lysvand, Kirsti Løseth, Veslemøy Malm Landsem, Janne Fossum Malmring, Valentyn Oksenych, Sten Even Erlandsen, Per Arne Aas, Lars Hagen, Caroline H. Pettersen, Tanel Tenson, Jan Egil Afset, Svein Arne Nordbø, Magnar Bjørås and Denis E. Kainov
Viruses 2020, 12(6), 642; https://0-doi-org.brum.beds.ac.uk/10.3390/v12060642 - 13 Jun 2020
Cited by 83 | Viewed by 15309
Abstract
As of June 2020, the number of people infected with severe acute respiratory coronavirus 2 (SARS-CoV-2) continues to skyrocket, with more than 6.7 million cases worldwide. Both the World Health Organization (WHO) and United Nations (UN) has highlighted the need for better control [...] Read more.
As of June 2020, the number of people infected with severe acute respiratory coronavirus 2 (SARS-CoV-2) continues to skyrocket, with more than 6.7 million cases worldwide. Both the World Health Organization (WHO) and United Nations (UN) has highlighted the need for better control of SARS-CoV-2 infections. However, developing novel virus-specific vaccines, monoclonal antibodies and antiviral drugs against SARS-CoV-2 can be time-consuming and costly. Convalescent sera and safe-in-man broad-spectrum antivirals (BSAAs) are readily available treatment options. Here, we developed a neutralization assay using SARS-CoV-2 strain and Vero-E6 cells. We identified the most potent sera from recovered patients for the treatment of SARS-CoV-2-infected patients. We also screened 136 safe-in-man broad-spectrum antivirals against the SARS-CoV-2 infection in Vero-E6 cells and identified nelfinavir, salinomycin, amodiaquine, obatoclax, emetine and homoharringtonine. We found that a combination of orally available virus-directed nelfinavir and host-directed amodiaquine exhibited the highest synergy. Finally, we developed a website to disseminate the knowledge on available and emerging treatments of COVID-19. Full article
(This article belongs to the Special Issue Antiviral Drug Combinations)
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