{"id":3030,"date":"2022-03-22T15:42:57","date_gmt":"2022-03-22T22:42:57","guid":{"rendered":"https:\/\/onlineacademiccommunity.uvic.ca\/ialh\/?p=3030"},"modified":"2022-03-22T15:42:57","modified_gmt":"2022-03-22T22:42:57","slug":"shapify-pathways-to-sars-cov-2-frameshifting-pseudoknot","status":"publish","type":"post","link":"https:\/\/onlineacademiccommunity.uvic.ca\/ialh\/shapify-pathways-to-sars-cov-2-frameshifting-pseudoknot\/","title":{"rendered":"Shapify: Pathways to SARS-CoV-2 Frameshifting Pseudoknot"},"content":{"rendered":"

Publication Alert!<\/strong> IALH Research Fellow Hosna Jabbari has co-authored an article with Luke Trinity, Ian Wark, Lance Lansing and Ulrike Stege entitled “Shapify: Pathways to SARS-CoV-2 Frameshifting Pseudoknot<\/em><\/span>“. The article was published with Research Square<\/em>.<\/p>\n

Abstract:<\/strong><\/p>\n

Background: Multiple viruses including HIV, MERS-CoV (coronavirus responsible for Middle East Respiratory Syndrome, MERS), SARS-CoV (coronavirus responsible for SARS) and SARS-CoV-2 (coronavirus responsible for COVID-19) use a mechanism known as \u22121 programmed ribosomal frameshifting (\u22121 PRF) to successfully replicate. SARS-CoV-2 possesses a unique RNA pseudoknotted structure that stimulates \u22121 PRF. Recent experiments identified small molecules as antiviral agents that can bind to the pseudoknot and disrupt its stimulation of \u22121 PRF. Targeting \u22121 PRF in SARS-CoV-2 to impair viral replication can improve patients\u2019 prognoses. Crucial to developing these successful therapies is modeling the structure of the SARS-CoV-2 \u22121 PRF pseudoknot. Our goal is to expand knowledge of possible pseudoknot conformations. Results: Following a structural alignment approach, we identify similarities in \u22121 PRF pseudoknots of SARS-CoV-2, SARS-CoV, and MERS-CoV. We introduce Shapify, a novel algorithm that given an RNA sequence incorporates structural reactivity (SHAPE) data and partial structure information to output an RNA secondary structure prediction within a biologically sound hierarchical folding approach. Shapify helps us to better understand non-native SARS-CoV-2 \u22121 PRF pseudoknot conformations that are relevant to structure function and may correlate with \u22121 PRF efficiency. We provide in-depth analysis by investigating the structural landscape for the SARS-CoV-2 \u22121 PRF pseudoknot, including reference and mutated sequences. To better understand the impact of mutations, we provide insight on SARS-CoV-2 \u22121 PRF pseudoknot sequence mutations and their effect on the resulting structure. Conclusion: We identify the consensus structure for SARS-CoV, SARS-CoV-2, and MERS-CoV \u22121 PRF pseudoknots; this similarity in functional RNA structures aids treatment preparation for existing and emergent viruses. Shapify predictions are guided both by SHAPE data and partial structure information. Applied to the SARS-CoV-2 \u22121 PRF pseudoknot, Shapify unveiled previously unknown pathways from initial stems to pseudoknotted secondary structures. Where SHAPE data is unavailable we provide predictions for noteworthy SARS-CoV-2 \u22121 PRF mutated pseudoknot sequences. By contextualizing our work with available experimental data, our structure predictions motivate future RNA structure-function research and can aid 3-D modeling of pseudoknots.<\/p>\n

To read the full article, see https:\/\/ieeexplore.ieee.org\/abstract\/document\/9565715<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Publication Alert! IALH Research Fellow Hosna Jabbari has co-authored an article with Luke Trinity, Ian Wark, Lance Lansing and Ulrike Stege entitled “Shapify: Pathways to SARS-CoV-2 Frameshifting Pseudoknot“. The article was published with Research Square. Abstract: Background: Multiple viruses including HIV, MERS-CoV (coronavirus responsible for Middle East Respiratory Syndrome, MERS), SARS-CoV (coronavirus responsible for SARS) … <\/p>\n

Continue reading “Shapify: Pathways to SARS-CoV-2 Frameshifting Pseudoknot”<\/span><\/a><\/p>\n","protected":false},"author":8486,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_et_pb_use_builder":"","_et_pb_old_content":"","_et_gb_content_width":"","footnotes":""},"categories":[1],"tags":[93],"class_list":["post-3030","post","type-post","status-publish","format-standard","hentry","category-health","tag-hosna-jabbari","entry"],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/onlineacademiccommunity.uvic.ca\/ialh\/wp-json\/wp\/v2\/posts\/3030","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/onlineacademiccommunity.uvic.ca\/ialh\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/onlineacademiccommunity.uvic.ca\/ialh\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/onlineacademiccommunity.uvic.ca\/ialh\/wp-json\/wp\/v2\/users\/8486"}],"replies":[{"embeddable":true,"href":"https:\/\/onlineacademiccommunity.uvic.ca\/ialh\/wp-json\/wp\/v2\/comments?post=3030"}],"version-history":[{"count":2,"href":"https:\/\/onlineacademiccommunity.uvic.ca\/ialh\/wp-json\/wp\/v2\/posts\/3030\/revisions"}],"predecessor-version":[{"id":3032,"href":"https:\/\/onlineacademiccommunity.uvic.ca\/ialh\/wp-json\/wp\/v2\/posts\/3030\/revisions\/3032"}],"wp:attachment":[{"href":"https:\/\/onlineacademiccommunity.uvic.ca\/ialh\/wp-json\/wp\/v2\/media?parent=3030"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/onlineacademiccommunity.uvic.ca\/ialh\/wp-json\/wp\/v2\/categories?post=3030"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/onlineacademiccommunity.uvic.ca\/ialh\/wp-json\/wp\/v2\/tags?post=3030"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}