Investigation of ACE-2 Receptor Variations in Large Ruminants Raised in Türkiye and Analysis of Their Interaction with SARS-CoV-2 in Terms of COVID-19 Transmission Potential

Project no. 28511 · Status: Kapanmış (Yayın bekleniyor) · 2023

Summary

Hosts other than humans that may interact with SARS-CoV-2 (such as sheep, goats, cattle, cats, and dogs) have attracted significant interest from the international scientific community. A project proposal submitted by the principal investigator to investigate the relevance of sheep and goats in terms of SARS-CoV-2 was evaluated and accepted under the TÜBİTAK 1001 program. However, due to budget constraints, large ruminants could not be included in that project.In this project, the following aims are proposed:<ol><li data-list="ordered">To isolate RNA and synthesize cDNA from two cattle breeds with high representativeness in Türkiye (Bozırk n=40, Holstein n=40) and from water buffaloes (Anatolian buffalo n=40), followed by sequencing of the ACE2 gene;</li><li data-list="ordered">To detect mutations on the ACE2 protein through sequence data analysis;</li><li data-list="ordered">To investigate the binding affinities of these ACE2 variations with the spike proteins of SARS-CoV-2 variants (Wuhan, Alpha, Delta, and Omicron) using advanced bioinformatics approaches;</li><li data-list="ordered">To validate the strong or weak binding affinities/interactions detected in silico—especially between cattle ACE2 variants and the highly contagious Omicron variant—through in vitro testing;</li><li data-list="ordered">To screen for the presence of SARS-CoV-2 RNA in swab samples collected from animals;</li><li data-list="ordered">To investigate the presence of anti-SARS-CoV-2 IgG antibodies in serum samples.</li></ol>In conclusion:<ol><li data-list="ordered">This will be the first study worldwide to identify ACE2 receptor variations in cattle and buffaloes on a breed-specific basis.</li><li data-list="ordered">The binding affinities of ACE2 receptor variants with different SARS-CoV-2 variants will be revealed.</li><li data-list="ordered">The prevalence of SARS-CoV-2 RNA positivity and SARS-CoV-2 seroprevalence in cattle will be determined.</li></ol>Overall, when these findings are evaluated, large ruminants with potential to act as hosts or reservoirs for SARS-CoV-2 will be identified at the breed level within the One Health framework. Given that COVID-19 is expected to remain relevant for many years, a novel production platform/model will be developed for the first time, recommending that specific breeds (within each species) be isolated or have their production restricted during pandemics, while promoting the breeding of other, lower-risk breeds. This platform is also expected to contribute to reducing concerns about global food security risks anticipated over the next 50 years.

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