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Viruses
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Antivirals for Arboviruses
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Antivirals for Arboviruses

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Invertebrate Viruses".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 28286

Special Issue Editor

Dr. Leen Delang

E-Mail Website
Guest Editor
KU Leuven Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Herestraat 49, B-3000 Leuven, Belgium
Interests: arbovirology; antiviral research; infectious diseases; medical entomology

Special Issue Information

Dear Colleagues,

Arthropod-borne viruses (arboviruses) are a substantial threat to the health of humans and animals worldwide. Over the last few decades, the human population at risk for arthropod-borne infections has increased substantially. Up to 400 million people are infected every year with the dengue virus. Annually, millions of people are infected with other arboviruses such as the chikungunya virus and Zika virus. Furthermore, arboviruses are expected to become increasingly prevalent in more temperate regions such as Europe, resulting in even more people at risk.

Despite the significant burden on global health, antiviral therapies are currently not available for the treatment of arbovirus infections. Experimental inhibitors have been identified for several arboviruses, but only a few of those have advanced into clinical trials. Given the worldwide impact of arbovirus infections, the development of anti-arboviral drugs is urgently needed and expected to further gain momentum.

This Special Issue of Viruses aims to highlight recent advances in the discovery and design of new inhibitors against arboviruses. We also aim to explore new antiviral strategies for combating arbovirus infections.

Dr. Leen Delang
Guest Editor

Manuscript Submission Information

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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
  • broad-spectrum antivirals
  • antiviral strategies
  • drug-resistant viruses
  • host-targeting antivirals
  • arthropod-borne viruses
  • arboviruses

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Related Special Issue

Published Papers (7 papers)

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Research

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14 pages, 2323 KiB  
Article
Cranberry Pomace Extract Exerts Antiviral Activity against Zika and Dengue Virus at Safe Doses for Adult Zebrafish
by Laura Tamkutė, Juliano G. Haddad, Nicolas Diotel, Philippe Desprès, Petras Rimantas Venskutonis and Chaker El Kalamouni
Viruses 2022, 14(5), 1101; https://doi.org/10.3390/v14051101 - 20 May 2022
Cited by 10 | Viewed by 3220
Abstract
Mosquito-borne dengue virus (DENV) and zika virus (ZIKV) infections constitute a global health emergency. Antivirals directly targeting the virus infectious cycle are still needed to prevent dengue hemorrhagic fever and congenital zika syndrome. In the present study, we demonstrated that Cranberry Pomace (CP) [...] Read more.
Mosquito-borne dengue virus (DENV) and zika virus (ZIKV) infections constitute a global health emergency. Antivirals directly targeting the virus infectious cycle are still needed to prevent dengue hemorrhagic fever and congenital zika syndrome. In the present study, we demonstrated that Cranberry Pomace (CP) extract, a polyphenol-rich agrifood byproduct recovered following cranberry juice extraction, blocks DENV and ZIKV infection in human Huh7.5 and A549 cell lines, respectively, in non-cytotoxic concentrations. Our virological assays identified CP extract as a potential inhibitor of virus entry into the host-cell by acting directly on viral particles, thus preventing their attachment to the cell surface. At effective antiviral doses, CP extract proved safe and tolerable in a zebrafish model. In conclusion, polyphenol-rich agrifood byproducts such as berry extracts are a promising source of safe and naturally derived nutraceutical antivirals that target medically important pathogens. Full article
(This article belongs to the Special Issue Antivirals for Arboviruses)
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11 pages, 1648 KiB  
Article
Brevinin-2GHk, a Peptide Derived from the Skin of Fejervarya limnocharis, Inhibits Zika Virus Infection by Disrupting Viral Integrity
by Weichen Xiong, Jingyan Li, Yifei Feng, Jinwei Chai, Jiena Wu, Yunrui Hu, Maolin Tian, Wancheng Lu, Xueqing Xu and Min Zou
Viruses 2021, 13(12), 2382; https://doi.org/10.3390/v13122382 - 28 Nov 2021
Cited by 15 | Viewed by 2815
Abstract
Several years have passed since the Zika virus (ZIKV) pandemic reoccurred in 2015–2016. However, there is still a lack of proved protective vaccines or effective drugs against ZIKV. The peptide brevinin-2GHk (BR2GK), pertaining to the brevinin-2 family of antimicrobial peptides, has been reported [...] Read more.
Several years have passed since the Zika virus (ZIKV) pandemic reoccurred in 2015–2016. However, there is still a lack of proved protective vaccines or effective drugs against ZIKV. The peptide brevinin-2GHk (BR2GK), pertaining to the brevinin-2 family of antimicrobial peptides, has been reported to exhibit only weak antibacterial activity, and its antiviral effects have not been investigated. Thus, we analyzed the effect of BR2GK on ZIKV infection. BR2GK showed significant inhibitory activity in the early and middle stages of ZIKV infection, with negligible cytotoxicity. Furthermore, BR2GK was suggested to bind with ZIKV E protein and disrupt the integrity of the envelope, thus directly inactivating ZIKV. In addition, BR2GK can also penetrate the cell membrane, which may contribute to inhibition of the middle stage of ZIKV infection. BR2GK blocked ZIKV E protein expression with an IC50 of 3.408 ± 0.738 μΜ. In summary, BR2GK was found to be a multi-functional candidate and a potential lead compound for further development of anti-ZIKV drugs. Full article
(This article belongs to the Special Issue Antivirals for Arboviruses)
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17 pages, 5958 KiB  
Article
Favipiravir Inhibits Mayaro Virus Infection in Mice
by Michèle Bengue, Ai-rada Pintong, Florian Liegeois, Antoine Nougairède, Rodolphe Hamel, Julien Pompon, Xavier de Lamballerie, Pierre Roques, Valérie Choumet and Dorothée Missé
Viruses 2021, 13(11), 2213; https://doi.org/10.3390/v13112213 - 3 Nov 2021
Cited by 6 | Viewed by 3031
Abstract
Mayaro virus (MAYV) is an emergent alphavirus that causes MAYV fever. It is often associated with debilitating symptoms, particularly arthralgia and myalgia. MAYV infection is becoming a considerable health issue that, unfortunately, lacks a specific antiviral treatment. Favipiravir, a broad-spectrum antiviral drug, has [...] Read more.
Mayaro virus (MAYV) is an emergent alphavirus that causes MAYV fever. It is often associated with debilitating symptoms, particularly arthralgia and myalgia. MAYV infection is becoming a considerable health issue that, unfortunately, lacks a specific antiviral treatment. Favipiravir, a broad-spectrum antiviral drug, has recently been shown to exert anti-MAYV activity in vitro. In the present study, the potential of Favipiravir to inhibit MAYV replication in an in vivo model was evaluated. Immunocompetent mice were orally administrated 300 mg/kg/dose of Favipiravir at pre-, concurrent-, or post-MAYV infection. The results showed a significant reduction in infectious viral particles and viral RNA transcripts in the tissues and blood of the pre- and concurrently treated infected mice. A significant reduction in the presence of both viral RNA transcript and infectious viral particles in the tissue and blood of pre- and concurrently treated infected mice was observed. By contrast, Favipiravir treatment post-MAYV infection did not result in a reduction in viral replication. Interestingly, Favipiravir strongly decreased the blood levels of the liver disease markers aspartate- and alanine aminotransferase in the pre- and concurrently treated MAYV-infected mice. Taken together, these results suggest that Favipiravir is a potent antiviral drug when administered in a timely manner. Full article
(This article belongs to the Special Issue Antivirals for Arboviruses)
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11 pages, 8377 KiB  
Communication
Evaluation of Antiviral Activity of Cyclic Ketones against Mayaro Virus
by Luciana S. Fernandes, Milene L. da Silva, Roberto S. Dias, Marcel S. da S. Lucindo, Ítalo E. P. da Silva, Cynthia C. Silva, Róbson R. Teixeira and Sérgio O. de Paula
Viruses 2021, 13(11), 2123; https://doi.org/10.3390/v13112123 - 21 Oct 2021
Cited by 7 | Viewed by 2830
Abstract
Mayaro virus (MAYV) is a neglected arthropod-borne virus found in the Americas. MAYV infection results in Mayaro fever, a non-lethal debilitating disease characterized by a strong inflammatory response affecting the joints and muscles. MAYV was once considered endemic to forested areas in Brazil [...] Read more.
Mayaro virus (MAYV) is a neglected arthropod-borne virus found in the Americas. MAYV infection results in Mayaro fever, a non-lethal debilitating disease characterized by a strong inflammatory response affecting the joints and muscles. MAYV was once considered endemic to forested areas in Brazil but has managed to adapt and spread to urban regions using new vectors, such as Aedes aegypti, and has the potential to cause serious epidemics in the future. Currently, there are no vaccines or specific treatments against MAYV. In this study, the antiviral activity of a series of synthetic cyclic ketones were evaluated for the first time against MAYV. Twenty-four compounds were screened in a cell viability assay, and eight were selected for further evaluation. Effective concentration (EC50) and selectivity index (SI) were calculated and compound 9-(5-(4-chlorophenyl]furan-2-yl)-3,6-dimethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2))-dione (9) (EC50 = 21.5 µmol·L−1, SI = 15.8) was selected for mechanism of action assays. The substance was able to reduce viral activity by approximately 70% in both pre-treatment and post-treatment assays. Full article
(This article belongs to the Special Issue Antivirals for Arboviruses)
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14 pages, 2577 KiB  
Article
In Silico Structure-Based Design of Antiviral Peptides Targeting the Severe Fever with Thrombocytopenia Syndrome Virus Glycoprotein Gn
by Shuo-Feng Yuan, Lei Wen, Kenn Ka-Heng Chik, Jiang Du, Zi-Wei Ye, Jian-Li Cao, Kai-Ming Tang, Rong-Hui Liang, Jian-Piao Cai, Cui-Ting Luo, Fei-Fei Yin, Gang Lu, Hin Chu, Mi-Fang Liang, Dong-Yan Jin, Kwok-Yung Yuen and Jasper Fuk-Woo Chan
Viruses 2021, 13(10), 2047; https://doi.org/10.3390/v13102047 - 11 Oct 2021
Cited by 2 | Viewed by 3465
Abstract
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus in Asia that causes severe disease. Despite its clinical importance, treatment options for SFTSV infection remains limited. The SFTSV glycoprotein Gn plays a major role in mediating virus entry into host [...] Read more.
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus in Asia that causes severe disease. Despite its clinical importance, treatment options for SFTSV infection remains limited. The SFTSV glycoprotein Gn plays a major role in mediating virus entry into host cells and is therefore a potential antiviral target. In this study, we employed an in silico structure-based strategy to design novel cyclic antiviral peptides that target the SFTSV glycoprotein Gn. Among the cyclic peptides, HKU-P1 potently neutralizes the SFTSV virion. Combinatorial treatment with HKU-P1 and the broad-spectrum viral RNA-dependent RNA polymerase inhibitor favipiravir exhibited synergistic antiviral effects in vitro. The in silico peptide design platform in this study may facilitate the generation of novel antiviral peptides for other emerging viruses. Full article
(This article belongs to the Special Issue Antivirals for Arboviruses)
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Review

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35 pages, 1611 KiB  
Review
Antivirals against the Chikungunya Virus
by Verena Battisti, Ernst Urban and Thierry Langer
Viruses 2021, 13(7), 1307; https://doi.org/10.3390/v13071307 - 5 Jul 2021
Cited by 44 | Viewed by 6875
Abstract
Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that has re-emerged in recent decades, causing large-scale epidemics in many parts of the world. CHIKV infection leads to a febrile disease known as chikungunya fever (CHIKF), which is characterised by severe joint pain and myalgia. [...] Read more.
Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that has re-emerged in recent decades, causing large-scale epidemics in many parts of the world. CHIKV infection leads to a febrile disease known as chikungunya fever (CHIKF), which is characterised by severe joint pain and myalgia. As many patients develop a painful chronic stage and neither antiviral drugs nor vaccines are available, the development of a potent CHIKV inhibiting drug is crucial for CHIKF treatment. A comprehensive summary of current antiviral research and development of small-molecule inhibitor against CHIKV is presented in this review. We highlight different approaches used for the identification of such compounds and further discuss the identification and application of promising viral and host targets. Full article
(This article belongs to the Special Issue Antivirals for Arboviruses)
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10 pages, 276 KiB  
Review
Crimean-Congo Hemorrhagic Fever Virus: Current Advances and Future Prospects of Antiviral Strategies
by Shiyu Dai, Fei Deng, Hualin Wang and Yunjia Ning
Viruses 2021, 13(7), 1195; https://doi.org/10.3390/v13071195 - 22 Jun 2021
Cited by 30 | Viewed by 4690
Abstract
Crimean-Congo hemorrhagic fever virus (CCHFV) is a widespread, tick-borne pathogen that causes Crimean-Congo hemorrhagic fever (CCHF) with high morbidity and mortality. CCHFV is transmitted to humans through tick bites or direct contact with patients or infected animals with viremia. Currently, climate change and [...] Read more.
Crimean-Congo hemorrhagic fever virus (CCHFV) is a widespread, tick-borne pathogen that causes Crimean-Congo hemorrhagic fever (CCHF) with high morbidity and mortality. CCHFV is transmitted to humans through tick bites or direct contact with patients or infected animals with viremia. Currently, climate change and globalization have increased the transmission risk of this biosafety level (BSL)-4 virus. The treatment options of CCHFV infection remain limited and there is no FDA-approved vaccine or specific antivirals, which urges the identification of potential therapeutic targets and the design of CCHF therapies with greater effort. In this article, we discuss the current progress and some future directions in the development of antiviral strategies against CCHFV. Full article
(This article belongs to the Special Issue Antivirals for Arboviruses)
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