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15 pages, 4625 KiB

Open AccessArticle

Favipiravir Treatment Prolongs Survival in a Lethal BALB/c Mouse Model of Ebinur Lake Virus Infection

by Jingke Geng, Nanjie Ren, Cihan Yang, Fei Wang, Doudou Huang, Sergio Rodriguez, Zhiming Yuan and Han Xia

Viruses 2024, 16(4), 631; https://doi.org/10.3390/v16040631 - 18 Apr 2024

Abstract

Orthobunyavirus is the largest and most diverse genus in the family Peribunyaviridae. Orthobunyaviruses are widely distributed globally and pose threats to human and animal health. Ebinur Lake virus (EBIV) is a newly classified Orthobunyavirus detected in China, Russia, and Kenya. This study explored [...] Read more.

Orthobunyavirus is the largest and most diverse genus in the family Peribunyaviridae. Orthobunyaviruses are widely distributed globally and pose threats to human and animal health. Ebinur Lake virus (EBIV) is a newly classified Orthobunyavirus detected in China, Russia, and Kenya. This study explored the antiviral effects of two broad-spectrum antiviral drugs, favipiravir and ribavirin, in a BALB/c mouse model. Favipiravir significantly improved the clinical symptoms of infected mice, reduced viral titer and RNA copies in serum, and extended overall survival. The median survival times of mice in the vehicle- and favipiravir-treated groups were 5 and 7 days, respectively. Favipiravir significantly reduced virus titers 10- to 100-fold in sera at all three time points compared to vehicle-treated mice. And favipiravir treatment effectively reduced the virus copies by approximately 10-fold across the three time points, relative to vehicle-treated mice. The findings expand the antiviral spectrum of favipiravir for orthobunyaviruses in vivo. Full article

(This article belongs to the Special Issue Antivirals against Arboviruses)

17 pages, 4636 KiB

Open AccessArticle

Antiviral and Virucidal Activities of Uncaria tomentosa (Cat’s Claw) against the Chikungunya Virus

by Raquel Curtinhas de Lima, Ligia Maria Marino Valente, Débora Familiar Macedo, Luzia Maria de-Oliveira-Pinto, Flavia Barreto dos Santos, José Luiz Mazzei, Antonio Carlos Siani, Priscila Conrado Guerra Nunes and Elzinandes Leal de Azeredo

Viruses 2024, 16(3), 369; https://doi.org/10.3390/v16030369 - 27 Feb 2024

Viewed by 759

Abstract

Uncaria tomentosa (UT) is a medicinal plant popularly known as cat’s claw belonging to the Rubiaceae family that has been reported to display antiviral and anti-inflammatory activities. The chikungunya virus (CHIKV) outbreaks constitute a Brazilian public health concern. CHIKV infection develops an abrupt [...] Read more.

Uncaria tomentosa (UT) is a medicinal plant popularly known as cat’s claw belonging to the Rubiaceae family that has been reported to display antiviral and anti-inflammatory activities. The chikungunya virus (CHIKV) outbreaks constitute a Brazilian public health concern. CHIKV infection develops an abrupt onset of fever, usually accompanied by a skin rash, besides incapacitating polyarthralgia. There is no vaccine available or treatment for CHIKV infection. The present study evaluates the hydroalcoholic extract of UT bark as a potential antiviral against CHIKV. The in vitro antiviral activity of the UT extract against the Brazilian CHIKV strain was assessed using quantitative reverse transcription polymerase chain reaction, flow cytometry, and plaque assay. Results obtained demonstrated that UT inhibits CHIKV infection in a dose-dependent manner. At the non-cytotoxic concentration of 100 µg/mL, UT exhibited antiviral activity above 90% as determined by plaque reduction assay, and it reduced the viral cytopathic effect. Similarly, a significant virucidal effect of 100 µg/mL UT was observed after 24 and 48 h post-infection. This is the first report on the antiviral activity of UT against CHIKV infection, and the data presented here suggests UT as a potential antiviral to treat CHIKV infection. Full article

(This article belongs to the Special Issue Antivirals against Arboviruses)

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13 pages, 1826 KiB

Open AccessArticle

Antiviral, Cytoprotective, and Anti-Inflammatory Effect of Ampelozizyphus amazonicus Ducke Ethanolic Wood Extract on Chikungunya Virus Infection

by Daniele C. P. Rocha, Tháyna Sisnande, Daniel Gavino-Leopoldino, Iris Paula Guimarães-Andrade, Fernanda F. Cruz, Iranaia Assunção-Miranda, Simony C. Mendonça, Gilda Guimarães Leitão, Rosineide Costa Simas, Ronaldo Mohana-Borges, Suzana Guimarães Leitão and Diego Allonso

Viruses 2023, 15(11), 2232; https://doi.org/10.3390/v15112232 - 09 Nov 2023

Viewed by 957

Abstract

Chikungunya fever, a debilitating disease caused by Chikungunya virus (CHIKV), is characterized by a high fever of sudden onset and an intense arthralgia that impairs individual regular activities. Although most symptoms are self-limited, long-term persistent arthralgia is observed in 30–40% of infected individuals. [...] Read more.

Chikungunya fever, a debilitating disease caused by Chikungunya virus (CHIKV), is characterized by a high fever of sudden onset and an intense arthralgia that impairs individual regular activities. Although most symptoms are self-limited, long-term persistent arthralgia is observed in 30–40% of infected individuals. Currently, there is no vaccine or specific treatment against CHIKV infection, so there is an urgent need for the discovery of new therapeutic options for CHIKF chronic cases. This present study aims to test the antiviral, cytoprotective, and anti-inflammatory activities of an ethanol extract (FF72) from Ampelozizyphus amazonicus Ducke wood, chemically characterized using mass spectrometry, which indicated the major presence of dammarane-type triterpenoid saponins. The major saponin in the extract, with a deprotonated molecule ion m/z 897 [M-H]⁻, was tentatively assigned as a jujubogenin triglycoside, a dammarane-type triterpenoid saponin. Treatment with FF72 resulted in a significant reduction in both virus replication and the production of infective virions in BHK-21-infected cells. The viability of infected cells was assessed using an MTT, and the result indicated that FF72 treatment was able to revert the toxicity mediated by CHIKV infection. In addition, FF72 had a direct effect on CHIKV, since the infectivity was completely abolished in the presence of the extract. FF72 treatment also reduced the expression of the major pro-inflammatory mediators overexpressed during CHIKV infection, such as IL-1β, IL-6, IL-8, and MCP-1. Overall, the present study elucidates the potential of FF72 to become a promising candidate of herbal medicine for alphaviruses infections. Full article

(This article belongs to the Special Issue Antivirals against Arboviruses)

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15 pages, 9042 KiB

Open AccessArticle

Identification of 2,4-Diaminoquinazoline Derivative as a Potential Small-Molecule Inhibitor against Chikungunya and Ross River Viruses

by Amrita Saha, Badri Narayan Acharya, Manmohan Parida, Nandita Saxena, Jaya Rajaiya and Paban Kumar Dash

Viruses 2023, 15(11), 2194; https://doi.org/10.3390/v15112194 - 31 Oct 2023

Viewed by 993

Abstract

Alphaviruses are serious zoonotic threats responsible for significant morbidity, causing arthritis or encephalitis. So far, no licensed drugs or vaccines are available to combat alphaviral infections. About 300,000 chikungunya virus (CHIKV) infections have been reported in 2023, with more than 300 deaths, including [...] Read more.

Alphaviruses are serious zoonotic threats responsible for significant morbidity, causing arthritis or encephalitis. So far, no licensed drugs or vaccines are available to combat alphaviral infections. About 300,000 chikungunya virus (CHIKV) infections have been reported in 2023, with more than 300 deaths, including reports of a few cases in the USA as well. The discovery and development of small-molecule drugs have been revolutionized over the last decade. Here, we employed a cell-based screening approach using a series of in-house small-molecule libraries to test for their ability to inhibit CHIKV replication. DCR 137, a quinazoline derivative, was found to be the most potent inhibitor of CHIKV replication in our screening assay. Both, the cytopathic effect, and immunofluorescence of infected cells were reduced in a dose-dependent manner with DCR 137 post-treatment. Most importantly, DCR 137 was more protective than the traditional ribavirin drug and reduced CHIKV plaque-forming units by several log units. CHIKV-E2 protein levels were also reduced in a dose-dependent manner. Further, DCR 137 was probed for its antiviral activity against another alphavirus, the Ross River virus, which revealed effective inhibition of viral replication. These results led to the identification of a potential quinazoline candidate for future optimization that might act as a pan-alphavirus inhibitor. Full article

(This article belongs to the Special Issue Antivirals against Arboviruses)

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11 pages, 3509 KiB

Open AccessArticle

Multi-epitope Antigen for Specific Serological Detection of Dengue Viruses

by Samuel Santos Pereira, Robert Andreata-Santos, Maria Fernanda de Castro-Amarante, Aléxia Adrianne Venceslau-Carvalho, Natiely Silva Sales, Mariângela de Oliveira Silva, Rúbens Prince dos Santos Alves, Patrícia Jungmann and Luís Carlos de Souza Ferreira

Viruses 2023, 15(9), 1936; https://doi.org/10.3390/v15091936 - 16 Sep 2023

Viewed by 991

Abstract

Dengue is an infectious disease of global health concern that continues to require surveillance. Serological testing has been used to investigate dengue-infected patients, but specificity is affected by the co-circulation of ZIKA virus (ZIKV), which shares extensive antigen similarities. The goal of this [...] Read more.

Dengue is an infectious disease of global health concern that continues to require surveillance. Serological testing has been used to investigate dengue-infected patients, but specificity is affected by the co-circulation of ZIKA virus (ZIKV), which shares extensive antigen similarities. The goal of this study was the development of a specific dengue virus (DENV) IgG ELISA based on a multi-epitope NS1-based antigen for antibody detection. The multi-epitope protein (T-ΔNS1), derived from a fragment of the NS1-protein of the four DENV serotypes, was expressed in Escherichia coli and purified via affinity chromatography. The antigenicity and specificity were evaluated with sera of mice infected with DENV-1–4 or ZIKV or after immunization with the recombinant ΔNS1 proteins. The performance of the T-ΔNS1-based IgG ELISA was also determined with human serum samples. The results demonstrate that the DENV T-ΔNS1 was specifically recognized by the serum IgG of dengue-infected mice or humans but showed no or reduced reactivity with ZIKV-infected subjects. Based on the available set of clinical samples, the ELISA based on the DENV T-ΔNS1 achieved 77.42% sensitivity and 88.57% specificity. The results indicate that the T-ΔNS1 antigen is a promising candidate for the development of specific serological analysis. Full article

(This article belongs to the Special Issue Antivirals against Arboviruses)

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19 pages, 2702 KiB

Open AccessArticle

Inhibitors of the Ubiquitin-Mediated Signaling Pathway Exhibit Broad-Spectrum Antiviral Activities against New World Alphaviruses

by Niloufar A. Boghdeh, Brittany McGraw, Michael D. Barrera, Carol Anderson, Haseebullah Baha, Kenneth H. Risner, Ifedayo V. Ogungbe, Farhang Alem and Aarthi Narayanan

Viruses 2023, 15(3), 655; https://doi.org/10.3390/v15030655 - 28 Feb 2023

Cited by 2 | Viewed by 1676

Abstract

New World alphaviruses including Venezuelan Equine Encephalitis Virus (VEEV) and Eastern Equine Encephalitis Virus (EEEV) are mosquito-transmitted viruses that cause disease in humans and equines. There are currently no FDA-approved therapeutics or vaccines to treat or prevent exposure-associated encephalitic disease. The ubiquitin proteasome [...] Read more.

New World alphaviruses including Venezuelan Equine Encephalitis Virus (VEEV) and Eastern Equine Encephalitis Virus (EEEV) are mosquito-transmitted viruses that cause disease in humans and equines. There are currently no FDA-approved therapeutics or vaccines to treat or prevent exposure-associated encephalitic disease. The ubiquitin proteasome system (UPS)-associated signaling events are known to play an important role in the establishment of a productive infection for several acutely infectious viruses. The critical engagement of the UPS-associated signaling mechanisms by many viruses as host–pathogen interaction hubs led us to hypothesize that small molecule inhibitors that interfere with these signaling pathways will exert broad-spectrum inhibitory activity against alphaviruses. We queried eight inhibitors of the UPS signaling pathway for antiviral outcomes against VEEV. Three of the tested inhibitors, namely NSC697923 (NSC), bardoxolone methyl (BARM) and omaveloxolone (OMA) demonstrated broad-spectrum antiviral activity against VEEV and EEEV. Dose dependency and time of addition studies suggest that BARM and OMA exhibit intracellular and post-entry viral inhibition. Cumulatively, our studies indicate that inhibitors of the UPS-associated signaling pathways exert broad-spectrum antiviral outcomes in the context of VEEV and EEEV infection, supporting their translational application as therapeutic candidates to treat alphavirus infections. Full article

(This article belongs to the Special Issue Antivirals against Arboviruses)

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20 pages, 6822 KiB

Open AccessArticle

Caffeic Acid Has Antiviral Activity against Ilhéus Virus In Vitro

by Marielena Vogel Saivish, Carolina Colombelli Pacca, Vivaldo Gomes da Costa, Gabriela de Lima Menezes, Roosevelt Alves da Silva, Liliane Nebo, Gislaine Celestino Dutra da Silva, Bruno Henrique Gonçalves de Aguiar Milhim, Igor da Silva Teixeira, Tiago Henrique, Natalia Franco Bueno Mistrão, Victor Miranda Hernandes, Nathalia Zini, Ana Carolina de Carvalho, Marina Alves Fontoura, Paula Rahal, Lívia Sacchetto, Rafael Elias Marques and Maurício Lacerda Nogueira

Viruses 2023, 15(2), 494; https://doi.org/10.3390/v15020494 - 10 Feb 2023

Cited by 6 | Viewed by 1826

Abstract

Ilhéus virus (ILHV) is a neglected mosquito-borne flavivirus. ILHV infection may lead to Ilhéus fever, an emerging febrile disease like dengue fever with the potential to evolve into a severe neurological disease characterized by meningoencephalitis; no specific treatments are available for this disease. [...] Read more.

Ilhéus virus (ILHV) is a neglected mosquito-borne flavivirus. ILHV infection may lead to Ilhéus fever, an emerging febrile disease like dengue fever with the potential to evolve into a severe neurological disease characterized by meningoencephalitis; no specific treatments are available for this disease. This study assessed the antiviral properties of caffeic acid, an abundant component of plant-based food products that is also compatible with the socioeconomic limitations associated with this neglected infectious disease. The in vitro activity of caffeic acid on ILHV replication was investigated in Vero and A549 cell lines using plaque assays, quantitative RT-PCR, and immunofluorescence assays. We observed that 500 µM caffeic acid was virucidal against ILHV. Molecular docking indicated that caffeic acid might interact with an allosteric binding site on the envelope protein. Full article

(This article belongs to the Special Issue Antivirals against Arboviruses)

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Review

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21 pages, 6713 KiB

Open AccessReview

Recent Advances in Antivirals for Japanese Encephalitis Virus

by Yongzhe Zhu, Shenglin Chen, Qilin Lurong and Zhongtian Qi

Viruses 2023, 15(5), 1033; https://doi.org/10.3390/v15051033 - 23 Apr 2023

Cited by 5 | Viewed by 3023

Abstract

Culex mosquitoes are the primary vectors of the Japanese encephalitis virus (JEV). Since its discovery in 1935, Japanese encephalitis (JE), caused by JEV, has posed a significant threat to human health. Despite the widespread implementation of several JEV vaccines, the transmission chain of [...] Read more.

Culex mosquitoes are the primary vectors of the Japanese encephalitis virus (JEV). Since its discovery in 1935, Japanese encephalitis (JE), caused by JEV, has posed a significant threat to human health. Despite the widespread implementation of several JEV vaccines, the transmission chain of JEV in the natural ecosystem has not changed, and the vector of transmission cannot be eradicated. Therefore, JEV is still the focus of attention for flaviviruses. At present, there is no clinically specific drug for JE treatment. JEV infection is a complex interaction between the virus and the host cell, which is the focus of drug design and development. An overview of antivirals that target JEV elements and host factors is presented in this review. In addition, drugs that balance antiviral effects and host protection by regulating innate immunity, inflammation, apoptosis, or necrosis are reviewed to treat JE effectively. Full article

(This article belongs to the Special Issue Antivirals against Arboviruses)

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20 pages, 434 KiB

Open AccessReview

Recent Advancements in Mosquito-Borne Flavivirus Vaccine Development

by Bingan Wu, Zhongtian Qi and Xijing Qian

Viruses 2023, 15(4), 813; https://doi.org/10.3390/v15040813 - 23 Mar 2023

Cited by 4 | Viewed by 2266

Abstract

Lately, the global incidence of flavivirus infection has been increasing dramatically and presents formidable challenges for public health systems around the world. Most clinically significant flaviviruses are mosquito-borne, such as the four serotypes of dengue virus, Zika virus, West Nile virus, Japanese encephalitis [...] Read more.

Lately, the global incidence of flavivirus infection has been increasing dramatically and presents formidable challenges for public health systems around the world. Most clinically significant flaviviruses are mosquito-borne, such as the four serotypes of dengue virus, Zika virus, West Nile virus, Japanese encephalitis virus and yellow fever virus. Until now, no effective antiflaviviral drugs are available to fight flaviviral infection; thus, a highly immunogenic vaccine would be the most effective weapon to control the diseases. In recent years, flavivirus vaccine research has made major breakthroughs with several vaccine candidates showing encouraging results in preclinical and clinical trials. This review summarizes the current advancement, safety, efficacy, advantages and disadvantages of vaccines against mosquito-borne flaviviruses posing significant threats to human health. Full article

(This article belongs to the Special Issue Antivirals against Arboviruses)

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