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Human Coronaviruses (HCoV-229E, HCoV-OC43, HCoV-NL63) Antiviral Services

Human coronaviruses (HCoVs) are enveloped RNA viruses that are zoonotic, including SARS-CoV, MERS-CoV, HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1. HCoVs are endemic (HCoV-229E, HCoV-NL63, HCoV-OC43 and HCoVHKU1). The classic target tissue of HCoVs is the respiratory tract. Unlike SARS-CoV, MERS-CoV, and SARS-CoV-2 which are associated with severe respiratory disease, these four common HCoVs typically cause mild to moderate upper respiratory disease, estimated to account for 15%-30% of common cold cases in humans. The RNA genome of HCoV-229E is approximately 27,240 nucleotides long with a poly(A) tail. The GC content is close to 38%. The HCoV-229E laboratory strain has 8 putative protein-coding genes with the characteristic gene order ORF1a, ORF1b, HE, S, ORF4a, ORF4b, E, M, and N. The first complete genome sequence of HCoV-OC43 consists of 30,738 nucleotides with a poly(A) tail. The GC content is 37%, and the characteristic gene order is ORF1a, ORF1b, NS2a, HE, S, NS5a, E, M and N. The HCoV-NL63 genome is 27,553 nucleotides in length with a poly (A) tail. The GC content is 34%, which is very low among all HCoVs. The genomic order is ORF1a, ORF1b, S, ORF3, E, M and N.

HCoV-229E, OC43 and NL63 can be processed in the BSL-2 laboratory. In theory, rapid antigen tests for HCoVs have the advantages of quick results and low cost, but based on experience with influenza viruses using this method, rapid antigen tests may suffer from low sensitivity. Serological tests are not routinely used for the diagnosis of HCoV infection due to the lack of commercial reagents, let alone commercial reagents that have undergone clinical trials and regulatory review processes. On the other hand, serological testing is important to understand the epidemiology of emerging HCoVs, including the burden and role of asymptomatic infections.

HCoV-replicationFigure 1. HCoV replication.

HCoV infection is initiated by the binding of virions to cellular receptors, which drives conformational changes in the S2 subunit in S and promotes fusion of the viral and cell membrane (Figure 1). The gRNA is the template for the translation of the polyproteins pp1a and pp1ab, which are cleaved to form non-structural proteins. Non-structural proteins induce rearrangement of the cell membrane to form double-membrane vesicles, in which the viral replication-transcription complex is anchored. Full-length gRNAs are replicated through a negative-sense intermediate, and a nested set of sgRNA species are synthesized through discontinuous transcription. These sgRNAs encode viral structural and accessory proteins. The viral products produced will be assembled in the ER/Golgi intermediate compartment and bud out to the plasma membrane in the form of smooth vesicles, which are expelled by exocytosis.

So far, there are no effective antiviral options to treat HCoV-229E, HCoV-OC43 or HCoV-NL63 infection. Most of the antiviral drugs currently designed for coronaviruses against SARS-CoV and have not been tested for inhibition of coronaviruses currently circulating in human populations. Several inhibitors are known to reduce in vitro replication of at least some coronaviruses, including HCoV-NL63 and/or HCoV-229E. These inhibitors act at various steps of the coronavirus replication cycle, such as receptor binding, membrane fusion, transcription, replication, and post-translational processing. For prevention, a broad-spectrum pan-coronavirus vaccine should be developed. Creative Diagnostics supports clients in HCoVs antiviral research and development with extensive knowledge, focusing on pathogen transmission, the reservoir and/or intermediate hosts, virus biology, and efficacy and toxicity of an efficient antiviral drug.

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References:

  1. Weil, T., Lawrenz, J., Seidel, A., Münch, J., & Müller, J. A. (2022). Immunodetection assays for the quantification of seasonal common cold coronaviruses OC43, NL63, or 229E infection confirm nirmatrelvir as broad coronavirus inhibitor. Antiviral Research, 105343.
  2. Van Der Hoek, L., Pyrc, K., Jebbink, M. F., Vermeulen-Oost, W., Berkhout, R. J., Wolthers, K. C., ... & Berkhout, B. (2004). Identification of a new human coronavirus. Nature medicine, 10(4), 368-373.
  3. Liu, D. X., Liang, J. Q., & Fung, T. S. (2021). Human coronavirus-229e,-oc43,-nl63, and-hku1 (coronaviridae). Encyclopedia of virology, 428.
  4. Kesheh, M. M., Hosseini, P., Soltani, S., & Zandi, M. (2022). An overview on the seven pathogenic human coronaviruses. Reviews in medical virology, 32(2), e2282.
  5. Loeffelholz, M. J., & Tang, Y. W. (2020). Laboratory diagnosis of emerging human coronavirus infections–the state of the art. Emerging microbes & infections, 9(1), 747-756.
  6. Zhao, X., Ding, Y., Du, J., & Fan, Y. (2020). 2020 update on human coronaviruses: one health, one world. Medicine in Novel Technology and Devices, 8, 100043.

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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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