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Viruses
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Vaccines and Treatments for Viral Hemorrhagic Fevers
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Vaccines and Treatments for Viral Hemorrhagic Fevers

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 (10 December 2023) | Viewed by 6204

Special Issue Editors

Dr. Jason E. Comer

E-Mail Website
Guest Editor
Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA
Interests: evaluating the efficacy of medical countermeasures against bacterial and viral agents
Special Issues, Collections and Topics in MDPI journals
Dr. Dylan M Johnson

E-Mail Website
Guest Editor
Department of Biotechnology and Bioengineering, Sandia National Laboratory, Livermore, CA 94550, USA
Interests: vaccine and antiviral therapy development for emerging RNA viruses; molecular mechanisms of arenavirus replication and pathogenicity

Special Issue Information

Dear Colleagues,

Viral hemorrhagic fevers (VHFs) are diseases with the common features of multisystem pathology often leading to multiorgan system failure, vascular leakage, hypovolemic shock, and cardiovascular collapse. VHFs are caused by enveloped RNA viruses of the Filoviridae and Flaviviridae families; the order Bunyavirales including Arenaviridae, Hantaviridae, Nairoviridae, and Phenuiviridae; and the Henipaviruses. Sporadic and recurrent (re-)emergence of these pathogens is an ongoing threat due to sporadic emergence from zoonotic reservoirs. The effects of global climate change on host and vector ecology are responsible for shifting the endemic ranges of VHFs. Additionally, person-to-person and nosocomial spread complicated by globalization and increased travel can hamper efforts to contain VHF outbreaks. In humans, these pathogens can cause severe, life-threatening disease and most often have no licensed preventative or therapeutic medical countermeasures.

This Special Issue is focused on highlighting research into vaccines and therapeutics targeting VHFs. Current research topics cover a wide variety of strategies for vaccine prophylaxis and post-exposure vaccination, antiviral therapy, and techniques to enhance patient care and provider safety during the treatment of VHFs. Additionally, recent and ongoing refinements to animal models of VHF disease are allowing better modeling and more efficient development of medical countermeasures. We welcome research manuscripts and review articles related to the development of vaccines and treatments for viral hemorrhagic fevers.

Dr. Dylan M Johnson
Dr. Jason E. Comer
Guest Editors

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

  • vaccines
  • therapeutics
  • animal models
  • viral hemorrhagic fevers
  • filoviruses
  • arenaviruses
  • henipaviruses

Published Papers (4 papers)

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Research

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14 pages, 2916 KiB  
Article
Computer-Selected Antiviral Compounds: Assessing In Vitro Efficacies against Rift Valley Fever Virus
by Cigdem Alkan, Terrence O’Brien, Victor Kenyon and Tetsuro Ikegami
Viruses 2024, 16(1), 88; https://doi.org/10.3390/v16010088 - 05 Jan 2024
Viewed by 1113
Abstract
Rift Valley fever is a zoonotic viral disease transmitted by mosquitoes, impacting both humans and livestock. Currently, there are no approved vaccines or antiviral treatments for humans. This study aimed to evaluate the in vitro efficacy of chemical compounds targeting the Gc fusion [...] Read more.
Rift Valley fever is a zoonotic viral disease transmitted by mosquitoes, impacting both humans and livestock. Currently, there are no approved vaccines or antiviral treatments for humans. This study aimed to evaluate the in vitro efficacy of chemical compounds targeting the Gc fusion mechanism. These compounds were identified through virtual screening of millions of commercially available small molecules using a structure-based artificial intelligence bioactivity predictor. In our experiments, a pretreatment with small molecule compounds revealed that 3 out of 94 selected compounds effectively inhibited the replication of the Rift Valley fever virus MP-12 strain in Vero cells. As anticipated, these compounds did not impede viral RNA replication when administered three hours after infection. However, significant inhibition of viral RNA replication occurred upon viral entry when cells were pretreated with these small molecules. Furthermore, these compounds exhibited significant inhibition against Arumowot virus, another phlebovirus, while showing no antiviral effects on tick-borne bandaviruses. Our study validates AI-based virtual high throughput screening as a rational approach for identifying effective antiviral candidates for Rift Valley fever virus and other bunyaviruses. Full article
(This article belongs to the Special Issue Vaccines and Treatments for Viral Hemorrhagic Fevers)
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23 pages, 6585 KiB  
Article
Cheminformatics Strategies Unlock Marburg Virus VP35 Inhibitors from Natural Compound Library
by Isra M. Alsaady, Leena H. Bajrai, Thamir A. Alandijany, Hattan S. Gattan, Mai M. El-Daly, Sarah A. Altwaim, Rahaf T. Alqawas, Vivek Dhar Dwivedi and Esam I. Azhar
Viruses 2023, 15(8), 1739; https://doi.org/10.3390/v15081739 - 15 Aug 2023
Cited by 7 | Viewed by 1614
Abstract
The Ebola virus and its close relative, the Marburg virus, both belong to the family Filoviridae and are highly hazardous and contagious viruses. With a mortality rate ranging from 23% to 90%, depending on the specific outbreak, the development of effective antiviral interventions [...] Read more.
The Ebola virus and its close relative, the Marburg virus, both belong to the family Filoviridae and are highly hazardous and contagious viruses. With a mortality rate ranging from 23% to 90%, depending on the specific outbreak, the development of effective antiviral interventions is crucial for reducing fatalities and mitigating the impact of Marburg virus outbreaks. In this investigation, a virtual screening approach was employed to evaluate 2042 natural compounds for their potential interactions with the VP35 protein of the Marburg virus. Average and worst binding energies were calculated for all 20 poses, and compounds that exhibited binding energies <−6 kcal/mol in both criteria were selected for further analysis. Based on binding energies, only six compounds (Estradiol benzoate, INVEGA (paliperidone), Isosilybin, Protopanaxadiol, Permethrin, and Bufalin) were selected for subsequent investigations, focusing on interaction analysis. Among these selected compounds, Estradiol benzoate, INVEGA (paliperidone), and Isosilybin showed strong hydrogen bonds, while the others did not. In this study, the compounds Myricetin, Isosilybin, and Estradiol benzoate were subjected to a molecular dynamics (MD) simulation and free binding energy calculation using MM/GBSA analysis. The reference component Myricetin served as a control. Estradiol benzoate exhibited the most stable and consistent root-mean-square deviation (RMSD) values, whereas Isosilybin showed significant fluctuations in RMSD. The compound Estradiol benzoate exhibited the lowest ΔG binding free energy (−22.89 kcal/mol), surpassing the control compound’s binding energy (−9.29 kcal/mol). Overall, this investigation suggested that Estradiol benzoate possesses favorable binding free energies, indicating a potential inhibitory mechanism against the VP35 protein of the Marburg virus. The study proposes that these natural compounds could serve as a therapeutic option for preventing Marburg virus infection. However, experimental validation is required to further corroborate these findings. Full article
(This article belongs to the Special Issue Vaccines and Treatments for Viral Hemorrhagic Fevers)
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22 pages, 4426 KiB  
Article
Investigating the Mechanism of Action of Anti-Dengue Compounds as Potential Binders of Zika Virus RNA-Dependent RNA Polymerase
by Thamir A. Alandijany, Mai M. El-Daly, Ahmed M. Tolah, Leena H. Bajrai, Aiah M. Khateb, Isra M. Alsaady, Sarah A. Altwaim, Amit Dubey, Vivek Dhar Dwivedi and Esam I. Azhar
Viruses 2023, 15(7), 1501; https://doi.org/10.3390/v15071501 - 04 Jul 2023
Cited by 5 | Viewed by 1540
Abstract
The World Health Organization (WHO) has designated the Zika virus (ZIKV) as a significant risk to the general public’s health. Currently, there are no vaccinations or medications available to treat or prevent infection with the Zika virus. Thus, it is urgently required to [...] Read more.
The World Health Organization (WHO) has designated the Zika virus (ZIKV) as a significant risk to the general public’s health. Currently, there are no vaccinations or medications available to treat or prevent infection with the Zika virus. Thus, it is urgently required to develop a highly efficient therapeutic molecule. In the presented study, a computationally intensive search was carried out to identify potent compounds that have the potential to bind and block the activity of ZIKV NS5 RNA-dependent RNA polymerase (RdRp). The anti-dengue chemical library was subjected to high-throughput virtual screening and MM/GBSA analysis in order to rate the potential candidates. The top three compounds were then chosen. According to the MM/GBSA analysis, compound 127042987 from the database had the highest binding affinity to the protein with a minimum binding free energy of −77.16 kcal/mole. Compound 127042987 had the most stable RMSD trend and the greatest number of hydrogen bond interactions when these chemical complexes were evaluated further under a 100 ns molecular dynamics simulation. Compound 127042987 displayed the best binding free energy (GBind) of −96.50 kcal/mol, surpassing the native ligand binding energy (−66.17 kcal/mole). Thereafter, an MM/GBSA binding free energy study was conducted to validate the stability of selected chemical complexes. Overall, this study illustrated that compound 127042987 showed preferred binding free energies, suggesting a possible inhibitory mechanism against ZIKV-RdRp. As per this study, it was proposed that compound 127042987 could be used as a therapeutic option to prevent Zika virus infection. These compounds need to be tested in experiments for further validation. Full article
(This article belongs to the Special Issue Vaccines and Treatments for Viral Hemorrhagic Fevers)
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Review

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15 pages, 313 KiB  
Review
The Importance of Lassa Fever and Its Disease Management in West Africa
by Rachel A. Reyna, Kirsten E. Littlefield, Nathan Shehu, Tomoko Makishima, Junki Maruyama and Slobodan Paessler
Viruses 2024, 16(2), 266; https://doi.org/10.3390/v16020266 - 07 Feb 2024
Viewed by 1314
Abstract
Lassa virus (LASV) is a zoonotic pathogen endemic throughout western Africa and is responsible for a human disease known as Lassa fever (LF). Historically, LASV has been emphasized as one of the greatest public health threats in West Africa, with up to 300,000 [...] Read more.
Lassa virus (LASV) is a zoonotic pathogen endemic throughout western Africa and is responsible for a human disease known as Lassa fever (LF). Historically, LASV has been emphasized as one of the greatest public health threats in West Africa, with up to 300,000 cases and 5000 associated deaths per year. This, and the fact that the disease has been reported in travelers, has driven a rapid production of various vaccine candidates. Several of these vaccines are currently in clinical development, despite limitations in understanding the immune response to infection. Alarmingly, the host immune response has been implicated in the induction of sensorineural hearing loss in LF survivors, legitimately raising safety questions about any future vaccines as well as efficacy in preventing potential hearing loss. The objective of this article is to revisit the importance and prevalence of LF in West Africa, with focus on Nigeria, and discuss current therapeutic approaches and ongoing vaccine development. In addition, we aim to emphasize the need for more scientific studies relating to LF-associated hearing loss, and to promote critical discussion about potential risks and benefits of vaccinating the population in endemic regions of West Africa. Full article
(This article belongs to the Special Issue Vaccines and Treatments for Viral Hemorrhagic Fevers)
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