Cited by 95Mosquito-borne diseases and controlViral Infections and VectorsEnzyme Structure and Function

Nonstructural Proteins of Alphavirus—Potential Targets for Drug Development

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Abu Bakar, Farhana, Ng, Lisa·2018·Viruses

Abstract

Alphaviruses are enveloped, positive single-stranded RNA viruses, typically transmitted by arthropods. They often cause arthralgia or encephalitic diseases in infected humans and there is currently no targeted antiviral treatment available. The re-emergence of alphaviruses in Asia, Europe, and the Americas over the last decade, including chikungunya and o’nyong’nyong viruses, have intensified the search for selective inhibitors. In this review, we highlight key molecular determinants within the alphavirus replication complex that have been identified as viral targets, focusing on their structure and functionality in viral dissemination. We also summarize recent structural data of these viral targets and discuss how these could serve as templates to facilitate structure-based drug design and development of small molecule inhibitors.

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  • saRNA contains a long ORF after 5′ UTR encoding the four NSPs (nsP1, nsP2, nsP3, and nsP4) of alphavirus that functions as an mRNA capping enzyme, an NTPase/helicase/protease, a macrodomain, or an RNA-dependent RNA polymerase (RDRP), respectively.

    “In terms of structures, in addition to the conventional elements of non-replicating mRNA, saRNA contains a long ORF after 5′ UTR encoding the four NSPs (nsP1, nsP2, nsP3, and nsP4) of alphavirus that functions as an mRNA capping enzyme, an NTPase/helicase/protease, a macrodomain, or an RNA-dependent RNA polymerase (RDRP), respectively.”

    From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [194]

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Authors
Abu Bakar, F., & Ng, L.
Affiliations
  • Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore 138648, Singapore
  • Agency for Science, Technology and Research (SG)
Corresponding author
Ng, Lisa
Venue
Viruses
Publisher
MDPI AG
Published
2018-02-09
Volume
10
Issue
2
Pages
71
ISSN
1999-4915 (ISSN-L)
OpenAlex
W2792586783
Cited by
95
References
123
Citations by year
2026: 10 · 2025: 9 · 2024: 15 · 2023: 8 · 2022: 11 · 2021: 18 · 2020: 8 · 2019: 13 · 2018: 2 · 2017: 1
FWCI
1.86
Type
journal article
Language
en
Open access
Locations
  • Viruses (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • National University of Singapore (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DR-NTU (Nanyang Technological University) (submittedVersion, cc-by)
Funders
  • Agency for Science, Technology and Research
  • Biomedical Research Council
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
  • Health Sciences › Medicine › Infectious Diseases › Viral Infections and Vectors
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
Keywords
alphavirus, non-structural proteins, antiviral drug targets, structure-based drug design, small molecule inhibitors, viral replication complex, chikungunya virus, O'nyong-nyong virus, arboviruses
MeSH terms
Alphavirus, Antiviral Agents, Humans, Virus Replication, Genome, Viral, Viral Nonstructural Proteins, Alphavirus Infections, Genomics, Drug Discovery

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