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Viruses2023; 15(2); 413; doi: 10.3390/v15020413

Advances in the Development of Small Molecule Antivirals against Equine Encephalitic Viruses.

Abstract: Venezuelan, western, and eastern equine encephalitic alphaviruses (VEEV, WEEV, and EEEV, respectively) are arboviruses that are highly pathogenic to equines and cause significant harm to infected humans. Currently, human alphavirus infection and the resulting diseases caused by them are unmitigated due to the absence of approved vaccines or therapeutics for general use. These circumstances, combined with the unpredictability of outbreaks-as exemplified by a 2019 EEE surge in the United States that claimed 19 patient lives-emphasize the risks posed by these viruses, especially for aerosolized VEEV and EEEV which are potential biothreats. Herein, small molecule inhibitors of VEEV, WEEV, and EEEV are reviewed that have been identified or advanced in the last five years since a comprehensive review was last performed. We organize structures according to host- versus virus-targeted mechanisms, highlight cellular and animal data that are milestones in the development pipeline, and provide a perspective on key considerations for the progression of compounds at early and later stages of advancement.
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Publication Date: 2023-02-01 PubMed ID: 36851628PubMed Central: PMC9958955DOI: 10.3390/v15020413Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article discusses recent advancements in the development of small molecule antivirals against the highly pathogenic equine encephalitic alphaviruses, for which currently there are no approved vaccines or therapeutics available.

Context and Background

  • The article addresses the high pathogenicity of equine encephalitic alphaviruses (including Venezuelan, western, and eastern variants), and how they cause significant harm to both equines and humans.
  • Currently, there are no approved therapies or vaccines for the treatment of human alphavirus infection, and this lack of medical preparation adds to the unpredictable and dangerous nature of outbreaks.
  • The authors mention an occurrence from 2019 where a surge in the eastern equine encephalitis virus (EEEV) in the United States led to the loss of 19 lives, further emphasizing the need for focused therapeutic research.

  • Specifically, the study pinpoints aerosolized Venezuelan and eastern equine encephalitic viruses as potential biothreats.

Objective and Methodology

  • The research article is essentially a detailed review dedicated to small molecule inhibitors that have been identified or developed against VEEV, WEEV, and EEEV in the past five years. This is framed as a timely update since the last comprehensive review.
  • The six-year period preceding the writing of this article is the focus mainly, as this is when significant advancements were made in relation to small molecular inhibitors.
  • The molecule structures are organized on the basis of whether they target host or virus mechanism—into host-targeted and virus-targeted mechanisms respectively.

Findings and Perspective

  • The review article highlights significant findings from cellular and animal data that mark key steps forward in the development process.
  • The authors also provide insights into the key considerations for the progression of compounds at early and later stages of advancement.
  • The path forward, according to the authors, is through continued research and development of antivirals against these alphaviruses, with the keep parameters being the considerations for progression at different stages of the research.

Cite This Article

APA
Ogorek TJ, Golden JE. (2023). Advances in the Development of Small Molecule Antivirals against Equine Encephalitic Viruses. Viruses, 15(2), 413. https://doi.org/10.3390/v15020413

Publication

Viruses
ISSN: 1999-4915
NlmUniqueID: 101509722
Country: Switzerland
Language: English
Volume: 15
Issue: 2
PII: 413

Researcher Affiliations

Ogorek, Tyler J
  • Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Golden, Jennifer E
  • Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
  • Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin-Madison, Madison, WI 53705, USA.

MeSH Terms

  • Animals
  • Horses
  • Humans
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Encephalomyelitis, Equine / drug therapy
  • Alphavirus
  • Disease Outbreaks
  • Venezuela

Grant Funding

  • U19 AI142762 / NIAID NIH HHS

Conflict of Interest Statement

J.E.G. is a co-inventor of ML336, BDGR-4, BDGR-5, BDGR-69-70, and compounds 7a, 7b, and 7o which are included in this review.

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