{"id":8598,"date":"2023-09-06T17:31:42","date_gmt":"2023-09-06T17:31:42","guid":{"rendered":"https:\/\/www.caltagmedsystems.co.uk\/information\/?p=8598"},"modified":"2023-09-06T17:31:43","modified_gmt":"2023-09-06T17:31:43","slug":"sars-cov-2-open-reading-frames-orfs","status":"publish","type":"post","link":"https:\/\/www.caltagmedsystems.co.uk\/information\/sars-cov-2-open-reading-frames-orfs\/","title":{"rendered":"SARS-CoV-2 Open Reading Frames (ORFs)"},"content":{"rendered":"\n

The SARS-CoV-2 genome is ~29 kb divided into 10 open reading frames (ORFs). Each of these ORFs (except seemingly ORF10) is translated in 29 different proteins.<\/h3>\n\n\n\n

ORF1<\/strong> is formed by two overlapping ORFs, ORF1a<\/strong> and ORF1b<\/strong>, which are cleaved into 16 nonstructural proteins (NSPs).<\/p>\n\n\n\n

ORF2<\/strong> encodes the Spike (S) glycoprotein.<\/p>\n\n\n\n

ORF3a<\/strong> and ORF3b<\/strong> encode themselves.<\/p>\n\n\n\n

ORF4<\/strong> encodes the Envelope (E) protein.<\/p>\n\n\n\n

ORF5<\/strong> encodes the Membrane\/Matrix (M) protein.<\/p>\n\n\n\n

ORF6<\/strong> encodes itself.<\/p>\n\n\n\n

ORF7a<\/strong> and ORF7b<\/strong> are standalone proteins.<\/p>\n\n\n\n

ORF8<\/strong> encodes itself.<\/p>\n\n\n\n

ORF9<\/strong> is formed by three overlapping ORFs; ORF9a<\/strong> encodes the Nucleocapsid (N) protein and ORF9b<\/strong> and ORF9c<\/strong> encode themselves.<\/p>\n\n\n\n

ORF10<\/strong> seems to encode nothing of importance at this time.<\/p>\n\n\n\n

The Different ORF Proteins<\/h3>\n\n\n\n

The four structural proteins, S, M, N, and E comprise the matura virion. Sixteen non-structural proteins (NSPs_ and nine of the ten ORF proteins have various functions involved in viral replication, modulating the host cell cycle, and evading the host immune response. Summarised briefly here, is what is known and\/or postulated to date regarding the various SARS-CoV-2 ORF proteins:<\/p>\n\n\n\n

\u2013 ORF3a inhibits autophagy by preventing autolysosome formations. Forms homotetrameric potassium-sensitive ion channels. (275 a.a.)<\/p>\n\n\n\n

\u2013 ORF3b inhibits activation of IFN-I through an unknown mechanism. Generates a strong host immune response. (22 a.a.)<\/p>\n\n\n\n

\u2013 ORF6 inhibits activation of IFN-I by blocking nuclear translocation of transcription factors. (61 a.a.)<\/p>\n\n\n\n

\u2013 ORF7a suppresses antigen-presentation in monocytes and after ubiquitination, suppresses STAT2 phosphorylation thereby inhibiting activation of IFN-I. (121 a.a.)<\/p>\n\n\n\n

\u2013 ORF7b inhibits activation of IFN-I by inhibiting phosphorylation of STAT1 and STAT2. May have leucine zipper functionality. (43 a.a.)<\/p>\n\n\n\n

\u2013 ORF8 downregulates MHC-I in vitro<\/em>, inhibiting antigen presentation. Also generates a strong host immune response. (121 a.a.)<\/p>\n\n\n\n

\u2013 ORF9b inhibits activation of IFN-I by targeting IKK? (NEMO) and TOM70. (97 a.a.)<\/p>\n\n\n\n

\u2013 ORF9c may interfere with IFN signalling, but it is still being investigated. (73 a.a.)<\/p>\n\n\n\n

\u2013 ORF10 is not essential for viral replication and variants without this are fully functional. (~38 a.a.)<\/p>\n\n\n\n

ProSci\u2019s COVID-19 Research<\/h3>\n\n\n\n

ProSci is committed to furthering global research efforts to understand this novel virus and the disease it causes by offering a broad catalogue of SARS-CoV-2 antibodies<\/a>, recombinant proteins<\/a>, and related research reagents. Current research shows that inhibiting some of the accessory proteins can aid in overcoming immune evasion and suppression thereby allowing the host to fight off the infection. Let ProSci’s antibodies and proteins help further your research into these potential treatment options.<\/p>\n\n\n\n

References<\/h3>\n\n\n\n

Ren, Y., Shu, T., Wu, D., Mu, J., Wang, C., Huang, M., Han, Y., Zhang, X.-Y., Zhou, W., Qiu, Y., & Zhou, X. (2020). The ORF3a protein of SARS-CoV-2 induces apoptosis in cells. Cellular & Molecular Immunology, 17(8), 881\u2013883. https:\/\/doi.org\/10.1038\/s41423-020-0485-9<\/a><\/p>\n\n\n\n

Issa, E., Merhi, G., Panossian, B., Salloum, T., & Tokajian, S. (2020). SARS-CoV-2 and ORF3a: Nonsynonymous Mutations, Functional Domains, and Viral Pathogenesis. MSystems, 5(3). https:\/\/doi.org\/10.1128\/msystems.00266-20<\/a><\/p>\n\n\n\n

Miao, G., Zhao, H., Li, Y., Ji, M., Chen, Y., Shi, Y., Bi, Y., Wang, P., & Zhang, H. (2021). ORF3a of the COVID-19 virus SARS-CoV-2 blocks HOPS complex-mediated assembly of the SNARE complex required for autolysosome formation. Developmental Cell, 56(4), 427-442.e5. https:\/\/doi.org\/10.1016\/j.devcel.2020.12.010<\/a><\/p>\n\n\n\n

Majumdar, P., & Niyogi, S. (2020). ORF3a mutation associated with higher mortality rate in SARS-CoV-2 infection. Epidemiology and Infection, 148. https:\/\/doi.org\/10.1017\/s0950268820002599<\/a><\/p>\n\n\n\n

Konno, Y., Kimura, I., Uriu, K., Fukushi, M., Irie, T., Koyanagi, Y., Sauter, D., Gifford, R. J., Nakagawa, S., & Sato, K. (2020). SARS-CoV-2 ORF3b Is a Potent Interferon Antagonist Whose Activity Is Increased by a Naturally Occurring Elongation Variant. Cell Reports, 32(12), 108185. https:\/\/doi.org\/10.1016\/j.celrep.2020.108185<\/a><\/p>\n\n\n\n

Hachim, A., Kavian, N., Cohen, C. A., Chin, A. W. H., Chu, D. K. W., Mok, C. K. P., Tsang, O. T. Y., Yeung, Y. C., Perera, R. A. P. M., Poon, L. L. M., Peiris, J. S. M., & Valkenburg, S. A. (2020). ORF8 and ORF3b antibodies are accurate serological markers of early and late SARS-CoV-2 infection. Nature Immunology, 21(10), 1293\u20131301. https:\/\/doi.org\/10.1038\/s41590-020-0773-7<\/a><\/p>\n\n\n\n

Miorin, L., Kehrer, T., Sanchez-Aparicio, M. T., Zhang, K., Cohen, P., Patel, R. S., Cupic, A., Makio, T., Mei, M., Moreno, E., Danziger, O., White, K. M., Rathnasinghe, R., Uccellini, M., Gao, S., Aydillo, T., Mena, I., Yin, X., Martin-Sancho, L., \u2026 Garc\u00eda-Sastre, A. (2020). SARS-CoV-2 Orf6 hijacks Nup98 to block STAT nuclear import and antagonize interferon signaling. Proceedings of the National Academy of Sciences, 117(45), 28344\u201328354. https:\/\/doi.org\/10.1073\/pnas.2016650117<\/a><\/p>\n\n\n\n

Li, J.-Y., Liao, C.-H., Wang, Q., Tan, Y.-J., Luo, R., Qiu, Y., & Ge, X.-Y. (2020). The ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 inhibit type I interferon signaling pathway. Virus Research, 286, 198074. https:\/\/doi.org\/10.1016\/j.virusres.2020.198074<\/a><\/p>\n\n\n\n

Lei, X., Dong, X., Ma, R., Wang, W., Xiao, X., Tian, Z., Wang, C., Wang, Y., Li, L., Ren, L., Guo, F., Zhao, Z., Zhou, Z., Xiang, Z., & Wang, J. (2020). Activation and evasion of type I interferon responses by SARS-CoV-2. Nature Communications, 11(1). https:\/\/doi.org\/10.1038\/s41467-020-17665-9<\/a><\/p>\n\n\n\n

Zhou, Z., Huang, C., Zhou, Z., Huang, Z., Su, L., Kang, S., Chen, X., Chen, Q., He, S., Rong, X., Xiao, F., Chen, J., & Chen, S. (2021). Structural insight reveals SARS-CoV-2 ORF7a as an immunomodulating factor for human CD14+ monocytes. IScience, 24(3), 102187. https:\/\/doi.org\/10.1016\/j.isci.2021.102187<\/a><\/p>\n\n\n\n

Cao, Z., Xia, H., Rajsbaum, R., Xia, X., Wang, H., & Shi, P.-Y. (2021). Ubiquitination of SARS-CoV-2 ORF7a promotes antagonism of interferon response. Cellular & Molecular Immunology, 18(3), 746\u2013748. https:\/\/doi.org\/10.1038\/s41423-020-00603-6<\/a><\/p>\n\n\n\n

Nizamudeen, Z. A., Xu, E.-R., Karthik, V., Halawa, M., Arkill, K. P., Jackson, A. M., Bates, D. O., & Emsley, J. (2021). Structural assessment of SARS-CoV2 accessory protein ORF7a predicts LFA-1 and Mac-1 binding potential. Bioscience Reports, 41(1). https:\/\/doi.org\/10.1042\/bsr20203837<\/a><\/p>\n\n\n\n

Fogeron, M.-L., Montserret, R., Zehnder, J., Nguyen, M.-H., Dujardin, M., Brigandat, L., Cole, L., Ninot-Pedrosa, M., Lecoq, L., Meier, B. H., & B\u00f6ckmann, A. (2021). SARS-CoV-2 ORF7b: is a bat virus protein homologue a major cause of COVID-19 symptoms? Cold Spring Harbor Laboratory. https:\/\/doi.org\/10.1101\/2021.02.05.428650<\/a><\/p>\n\n\n\n

Xia, H., Cao, Z., Xie, X., Zhang, X., Chen, J. Y.-C., Wang, H., Menachery, V. D., Rajsbaum, R., & Shi, P.-Y. (2020). Evasion of Type I Interferon by SARS-CoV-2. Cell Reports, 33(1), 108234. https:\/\/doi.org\/10.1016\/j.celrep.2020.108234<\/a><\/p>\n\n\n\n

Flower, T. G., Buffalo, C. Z., Hooy, R. M., Allaire, M., Ren, X., & Hurley, J. H. (2020). Structure of SARS-CoV-2 ORF8, a rapidly evolving immune evasion protein. Proceedings of the National Academy of Sciences, 118(2), e2021785118. https:\/\/doi.org\/10.1073\/pnas.2021785118<\/a><\/p>\n\n\n\n

Hachim, A., Kavian, N., Cohen, C. A., Chin, A. W. H., Chu, D. K. W., Mok, C. K. P., Tsang, O. T. Y., Yeung, Y. C., Perera, R. A. P. M., Poon, L. L. M., Peiris, J. S. M., & Valkenburg, S. A. (2020). ORF8 and ORF3b antibodies are accurate serological markers of early and late SARS-CoV-2 infection. Nature Immunology, 21(10), 1293\u20131301. https:\/\/doi.org\/10.1038\/s41590-020-0773-7<\/a><\/p>\n\n\n\n

Neches, R. Y., Kyrpides, N. C., & Ouzounis, C. A. (2021). Atypical Divergence of SARS-CoV-2 Orf8 from Orf7a within the Coronavirus Lineage Suggests Potential Stealthy Viral Strategies in Immune Evasion. MBio, 12(1). https:\/\/doi.org\/10.1128\/mbio.03014-20<\/a><\/p>\n\n\n\n

Zinzula, L. (2021). Lost in deletion: The enigmatic ORF8 protein of SARS-CoV-2. Biochemical and Biophysical Research Communications, 538, 116\u2013124. https:\/\/doi.org\/10.1016\/j.bbrc.2020.10.045<\/a><\/p>\n\n\n\n

Wu, J., Shi, Y., Pan, X., Wu, S., Hou, R., Zhang, Y., Zhong, T., Tang, H., Du, W., Wang, L., Wo, J., Mu, J., Qiu, Y., Yang, K., Zhang, L.-K., Ye, B.-C., & Qi, N. (2021). SARS-CoV-2 ORF9b inhibits RIG-I-MAVS antiviral signaling by interrupting K63-linked ubiquitination of NEMO. Cell Reports, 34(7), 108761. https:\/\/doi.org\/10.1016\/j.celrep.2021.108761<\/a><\/p>\n\n\n\n

Jiang, H., Zhang, H., Meng, Q., Xie, J., Li, Y., Chen, H., Zheng, Y., Wang, X., Qi, H., Zhang, J., Wang, P.-H., Han, Z.-G., & Tao, S. (2020). SARS-CoV-2 Orf9b suppresses type I interferon responses by targeting TOM70. Cellular & Molecular Immunology, 17(9), 998\u20131000. https:\/\/doi.org\/10.1038\/s41423-020-0514-8<\/a><\/p>\n\n\n\n

Dominguez Andres, A., Feng, Y., Campos, A. R., Yin, J., Yang, C.-C., James, B., Murad, R., Kim, H., Deshpande, A. J., Gordon, D. E., Krogan, N., Pippa, R., & Ronai, Z. A. (2020). SARS-CoV-2 ORF9c Is a Membrane-Associated Protein that Suppresses Antiviral Responses in Cells. Cold Spring Harbor Laboratory. https:\/\/doi.org\/10.1101\/2020.08.18.256776<\/a><\/p>\n\n\n\n

Pancer, K., Milewska, A., Owczarek, K., Dabrowska, A., Kowalski, M., ?abaj, P. P., Branicki, W., Sanak, M., & Pyrc, K. (2020). The SARS-CoV-2 ORF10 is not essential in vitro or in vivo in humans. PLOS Pathogens, 16(12), e1008959. https:\/\/doi.org\/10.1371\/journal.ppat.1008959<\/a><\/p>\n\n\n\n

Originally posted by ProSci on https:\/\/www.prosci-inc.com\/blog\/sars-cov-2-orfs\/<\/a><\/p>\n\n\n\n

Caltag Medsystems <\/a>is the distributor of ProSci <\/a>products in the UK and Ireland. If you have any questions about these products, please contact us<\/a>.<\/p>\n","protected":false},"excerpt":{"rendered":"

The SARS-CoV-2 genome is ~29 kb divided into 10 ORFs. Each of these ORFs (except seemingly ORF10) is translated in 29 different proteins.<\/p>\n","protected":false},"author":13,"featured_media":8344,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[517,1],"tags":[515,711,77,518],"class_list":["post-8598","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-covid-19","category-general-information","tag-covid-19","tag-orfs","tag-prosci","tag-sars-cov-2"],"_links":{"self":[{"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/posts\/8598","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/users\/13"}],"replies":[{"embeddable":true,"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/comments?post=8598"}],"version-history":[{"count":3,"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/posts\/8598\/revisions"}],"predecessor-version":[{"id":8606,"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/posts\/8598\/revisions\/8606"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/media\/8344"}],"wp:attachment":[{"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/media?parent=8598"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/categories?post=8598"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.caltagmedsystems.co.uk\/information\/wp-json\/wp\/v2\/tags?post=8598"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}