The SARS-CoV-2 Spike protein has a broad tropism for mammalian ACE2 proteins

• DOI: 10.1371/journal.pbio.3001016
• Publication Date: 2020-12-21T18:27:11Z
• Authors: Carina Conceicao; Nazia Thakur; Stacey Human; James T. Kelly; Leanne Logan; Dagmara Bialy; Sushant Bhat; Phoebe Stevenson-...; Adrian K. Zagrajek; Philippa Hollingh...; Michal Varga; Christina Tsirigoti; Matthew Tully; Chris Chiu; Katy Moffat; Adrian Paul Silesian; John A. Hammond; Helena J. Maier; Erica Bickerton; Holly Shelton; Isabelle Dietrich; Stephen C. Graham; Dalan Bailey
• Keywords: Coronavirus; Tissue tropism; Angiotensin-converting enzyme 2; Betacoronavirus; Novel virus

SARS Coronavirus 2 (SARS-CoV-2) emerged in late 2019, leading to the Disease 2019 (COVID-19) pandemic that continues cause significant global mortality human populations. Given its sequence similarity SARS-CoV, as well related coronaviruses circulating bats, SARS-CoV-2 is thought have originated Chiroptera species China. However, whether virus spread directly humans or through an intermediate host currently unclear, potential for this infect companion animals, livestock, and wildlife could act viral reservoirs. Using a combination of surrogate entry assays live virus, we demonstrate that, addition angiotensin-converting enzyme (ACE2), Spike glycoprotein has broad tropism mammalian ACE2 receptors, despite divergence amino acids at receptor binding site on these proteins. Of 22 different hosts investigated, proteins from dog, cat, cattle were most permissive SARS-CoV-2, while bat bird least efficiently used receptors. The absence any 3 genetically distinct examined indicates usage likely shifted during zoonotic transmission bats into people, possibly reservoir. Comparison SARS-CoV RaTG13 identified tropisms, with viruses being more closely aligned. Finally, using bioinformatics, structural data, targeted mutagenesis, acid residues within Spike–ACE2 interface, which may played pivotal role emergence humans. apparently point confirms risk infection wide range wildlife.