Recent Advances in Antivirals for Emerging Viruses 3.0

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Virology".

Deadline for manuscript submissions: 30 November 2024 | Viewed by 5594

Special Issue Editor


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Guest Editor
Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA, USA
Interests: antiviral agents; broad-spectrum antivirals; antiviral response; emerging and re-emerging viral diseases; antiviral strategies; druggable antiviral targets; direct acting antivirals; host-directed antivirals; drug-resistant viruses
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Special Issue Information

Dear Colleagues,

This Special Issue is the continuation of our previous Special Issue entitled "Recent Advances in Antivirals for Emerging Viruses", which was published in 2021 and 2023

The emergence of COVID-19 is a reminder that new transmissible viruses may have global social, health, and economic impacts. Recently developed biological tools (including rapid and efficient cloning and sequencing) have advanced scientific efforts to identify the viral enzymes of important novel and re-emerging human viruses (e.g., Dengue, West Nile, Zika, Chikungunya, influenza, and now coronaviruses). At the same time, drug discovery has expanded exponentially, resulting in vast libraries of compounds that can be employed to screen direct antiviral activity. This Special Issue will highlight recent advances in antiviral drug developments, and address the following domains:

  1. directly acting antivirals;
  2. modifiers of immune activation;
  3. inhibitors of specific cell activation pathways.

Dr. James J. Kohler
Guest Editor

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Keywords

  • antiviral agents
  • broad-spectrum antivirals
  • antiviral response
  • emerging and re-emerging viral diseases
  • antiviral strategies
  • druggable antiviral targets
  • direct acting antivirals
  • host-directed antivirals
  • drug-resistant viruses

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Published Papers (3 papers)

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Research

21 pages, 1546 KiB  
Article
Effect of Opaganib on Supplemental Oxygen and Mortality in Patients with Severe SARS-CoV-2 Based upon FIO2 Requirements
by Fernando Carvalho Neuenschwander, Ofra Barnett-Griness, Stefania Piconi, Yasmin Maor, Eduardo Sprinz, Nimer Assy, Oleg Khmelnitskiy, Nikita V. Lomakin, Boris Mikhailovich Goloshchekin, Ewelina Nahorecka, Adilson Joaquim Westheimer Calvacante, Anastasia Ivanova, Sergey Vladimirovich Zhuravel, Galina Yurevna Trufanova, Stefano Bonora, Amer Saffoury, Ami Mayo, Yury G. Shvarts, Giuliano Rizzardini, Rogerio Sobroza de Mello, Janaina Pilau, Alexey Klinov, Benjamin Valente-Acosta, Oleg Olegovich Burlaka, Natalia Bakhtina, Maskit Bar-Meir, Ivan Nikolaevich Shishimorov, Jose Oñate-Gutierrez, Cristian Iván García Rincón, Tatiana Ivanovna Martynenko, Ludhmila Abrahão Hajjar, Ana Carolina Nazare de Mendonca Procopio, Krzysztof Simon, Walter Gabriel Chaves Santiago, Adam Fronczak, Conrado Roberto Hoffmann Filho, Osama Hussein, Vladimir Aleksandrovich Martynov, Guido Chichino, Piotr Blewaska, Jacek Wroblewski, Sergio Saul Irizar Santana, Andres Felipe Ocampo Agudelo, Adam Barczyk, Rachael lask Gerlach, Eppie Campbell, Aida Bibliowicz, Reza Fathi, Patricia Anderson, Gilead Raday, Michal Klein, Clara Fehrmann, Gina Eagle, Vered Katz Ben-Yair and Mark L. Levittadd Show full author list remove Hide full author list
Microorganisms 2024, 12(9), 1767; https://doi.org/10.3390/microorganisms12091767 - 26 Aug 2024
Cited by 1 | Viewed by 1472
Abstract
Once a patient has been diagnosed with severe COVID-19 pneumonia, treatment options have limited effectiveness. Opaganib is an oral treatment under investigation being evaluated for treatment of hospitalized patients with severe COVID-19 pneumonia. A randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in [...] Read more.
Once a patient has been diagnosed with severe COVID-19 pneumonia, treatment options have limited effectiveness. Opaganib is an oral treatment under investigation being evaluated for treatment of hospitalized patients with severe COVID-19 pneumonia. A randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in 57 sites worldwide from August 2020 to July 2021. Patients received either opaganib (n = 230; 500 mg twice daily) or matching placebo (n = 233) for 14 days. The primary outcome was the proportion of patients no longer requiring supplemental oxygen by day 14. Secondary outcomes included changes in the World Health Organization Ordinal Scale for Clinical Improvement, viral clearance, intubation, and mortality at 28 and 42 days. Pre-specified primary and secondary outcome analyses did not demonstrate statistically significant benefit (except nominally for time to viral clearance). Post-hoc analysis revealed the fraction of inspired oxygen (FIO2) at baseline was prognostic for opaganib treatment responsiveness and corresponded to disease severity markers. Patients with FIO2 levels at or below the median value (≤60%) had better outcomes after opaganib treatment (n = 117) compared to placebo (n = 134). The proportion of patients with ≤60% FIO2 at baseline that no longer required supplemental oxygen (≥24 h) by day 14 of opaganib treatment increased (76.9% vs. 63.4%; nominal p-value = 0.033). There was a 62.6% reduction in intubation/mechanical ventilation (6.84% vs. 17.91%; nominal p-value = 0.012) and a clinically meaningful 62% reduction in mortality (5.98% vs. 16.7%; nominal p-value = 0.019) by day 42. No new safety concerns were observed. While the primary analyses were not statistically significant, post-hoc analysis suggests opaganib benefit for patients with severe COVID-19 requiring supplemental oxygen with an FIO2 of ≤60%. Further studies are warranted to prospectively confirm opaganib benefit in this subpopulation. Full article
(This article belongs to the Special Issue Recent Advances in Antivirals for Emerging Viruses 3.0)
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13 pages, 1379 KiB  
Article
Acute Hepatitis of Unknown Origin in Children: Analysis of 17 Cases Admitted to the Bambino Gesù Children’s Hospital in Rome
by Velia Chiara Di Maio, Leonarda Gentile, Rossana Scutari, Luna Colagrossi, Luana Coltella, Stefania Ranno, Giulia Linardos, Daniela Liccardo, Maria Sole Basso, Andrea Pietrobattista, Simona Landi, Lorena Forqué, Marta Ciofi Degli Atti, Lara Ricotta, Andrea Onetti Muda, Giuseppe Maggiore, Massimiliano Raponi, Carlo Federico Perno and Cristina Russo
Microorganisms 2024, 12(4), 826; https://doi.org/10.3390/microorganisms12040826 - 19 Apr 2024
Viewed by 1141
Abstract
This study described 17 cases of children admitted to the Bambino Gesù Children’s Hospital with acute hepatitis of unknown origin between mid-April and November 2022. Following the World Health Organization’s working case definition of probable cases, 17 children, with a median age of [...] Read more.
This study described 17 cases of children admitted to the Bambino Gesù Children’s Hospital with acute hepatitis of unknown origin between mid-April and November 2022. Following the World Health Organization’s working case definition of probable cases, 17 children, with a median age of 2.1 years (interquartile range: 1.0–7.1), presenting with acute hepatitis non-AE, with serum transaminase >500 IU/L, were included in the study. A pre-specified set of microbiological tests was performed on different biological specimens for all pediatric patients. All patients resulted negative for the common hepatotropic viruses. The most common pathogen detected in blood specimens was human-herpes-virus-7 (52.9%). Adenovirus was detected more frequently in stool specimens (62.5%) than in respiratory (20.0%) or blood samples (17.6%). Regarding Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, one child tested positive two days after admission, while antibodies against spike and nucleoprotein were present in 82.3% of patients. A co-pathogen detection was observed in 94.1% of children. Overall, 16 children recovered without clinical complications, while one patient required liver transplantation. In these cases of acute hepatitis of unknown origin, adenovirus was mainly detected in stool samples. A co-pathogen detection was also frequently observed, suggesting that the etiology of this acute hepatitis is most probably multifactorial. Full article
(This article belongs to the Special Issue Recent Advances in Antivirals for Emerging Viruses 3.0)
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18 pages, 2489 KiB  
Article
The Effect of Bifidobacterium animalis subsp. lactis Bl-04 on Influenza A Virus Infection in Mice
by Bryan Zabel, Sanna M. Mäkelä, Derek Nedveck, Ashley A. Hibberd, Nicolas Yeung, Sinikka Latvala, Liisa Lehtoranta, Jouni Junnila, Kevin B. Walters, Wesley Morovic and Markus J. Lehtinen
Microorganisms 2023, 11(10), 2582; https://doi.org/10.3390/microorganisms11102582 - 17 Oct 2023
Cited by 1 | Viewed by 2279
Abstract
Influenza A virus infection is a major global disease requiring annual vaccination. Clinical studies indicate that certain probiotics may support immune function against influenza and other respiratory viruses, but direct molecular evidence is scarce. Here, mice were treated with a placebo or Bifidobacterium [...] Read more.
Influenza A virus infection is a major global disease requiring annual vaccination. Clinical studies indicate that certain probiotics may support immune function against influenza and other respiratory viruses, but direct molecular evidence is scarce. Here, mice were treated with a placebo or Bifidobacterium animalis subsp. lactis Bl-04 (Bl-04) orally via food (cereal) and also by gavage and exposed to Influenza A virus H1N1 (H1N1). The symptoms of the infection were observed, and tissues and digesta were collected for viral load RT-qPCR, transcriptomics, and microbiomics. The treatment decreased the viral load by 48% at day 3 post-infection in lungs and symptoms of infection at day 4 compared to placebo. Tissue transcriptomics showed differences between the Bl-04 and placebo groups in the genes in the Influenza A pathway in the intestine, blood, and lungs prior to and post-infection, but the results were inconclusive. Moreover, 16S rRNA gene profiling and qPCR showed the presence of Bl-04 in the intestine, but without major shifts in the microbiome. In conclusion, Bl-04 treatment may influence the host response against H1N1 in a murine challenge model; however, further studies are required to elucidate the mechanism of action. Full article
(This article belongs to the Special Issue Recent Advances in Antivirals for Emerging Viruses 3.0)
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