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Alphaviruses Antiviral Services

Alphaviruses belong to the Togaviridae family. They are arboviruses transmitted to humans by Aedes aegypti and Aedes albopictus, and they cause various diseases, which can be broadly classified into arthritogenic and encephalitogenic. Old World alphaviruses such as Chikungunya virus (CHIKV), O'nyong'nyong virus (ONNV), and Sindbis virus (SINV) are triggers of arthritis, often causing febrile illness with rash, polyarthralgia, and chronic arthritis. Infections with New World alphaviruses, such as Eastern equine encephalitis (EEEV) and Venezuelan equine encephalitis virus (VEEV), are less prevalent in humans and are mainly associated with neurological disorders. Alphavirus is a small, enveloped RNA virus with a single-stranded, positive-sense RNA genome. The alphavirus genome is about 12kb in length and consists of two open reading frames (ORFs): a 7kb frame encodes non-structural polyprotein, and a 4kb frame encodes structural polyprotein. The nonstructural polyprotein is cleaved into four distinct proteins (nsP1, nsP2, nsp3, and nsp4) that are required for the transcription and translation of viral mRNA in the host cell cytoplasm.

No targeted antiviral treatment is currently available. In theory, all steps of the alphavirus replication cycle could be potential targets for antiviral drug development. These steps involve interactions between viral proteins and host factors. The main advantages of host-targeting antivirals are the potential broad-spectrum activity against multiple alphaviruses and the low likelihood of developing viral resistance. However, when targeting host factors, care must be taken to avoid (serious) side effects. The worldwide re-emergence of arthritis-causing alphaviruses and the high morbidity associated with their infection underscores the need for effective and safe antiviral drugs against these viruses. If timely and effective antiviral drugs are given, they can reduce the severity of disease symptoms during acute infection by reducing the viral load in infected patients. In addition, the use of antiviral drugs to reduce viremia in infected patients may indirectly limit mosquito transmission of the virus, thus potentially reducing the chance of a pandemic.

Creative Diagnostics facilitates alphaviruses antiviral research and development against mosquito-borne viruses, including Ross River virus, Sindbis virus, and Semliki Forest virus. Our in vitro testing services include viral screening tests as well as tests to evaluate promising candidates, including their range of action, the effectiveness of drug combinations, the potential for resistance selection, and phenotypic/genetic characterization of resistant strains. For in vivo efficacy studies, we provide in vivo model development and testing services. High-potential candidates can be rapidly identified through our screening assay, with simultaneous efficacy and cytotoxicity assessments.

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(Other viruses antiviral services may be available on request)

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For additional information about Alphaviruses Antiviral Services, please contact us.

References:

  1. Abu Bakar, F., & Ng, L. F. (2018). Nonstructural proteins of alphavirus—potential targets for drug development. Viruses, 10(2), 71.
  2. Abdelnabi, R., & Delang, L. (2020). Antiviral strategies against arthritogenic alphaviruses. Microorganisms, 8(9), 1365.

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Antiviral Services - Creative Diagnostics

Creative Diagnostics provides expertise in antiviral (or antibacterial) assays and cell-based antiviral (or antibacterial) compound screening to other biotechnology and pharmaceutical companies.

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