A Prenylated dsRNA Sensor Protects Against Severe COVID-19 and is Absent in Horseshoe Bats



Contributing to research themes:

Cell autonomous antiviral defenses can inhibit the replication of viruses and reduce transmission and disease severity. To better understand the antiviral response to SARS-CoV-2, we used interferon-stimulated gene (ISG) expression screening to reveal that OAS1, through RNase L, potently inhibits SARS-CoV-2. We show that while some people can express a prenylated OAS1 variant, that is membrane-associated and blocks SARS-CoV-2 infection, other people express a cytosolic, nonprenylated OAS1 variant which does not detect SARS-CoV-2 (determined by the splice-acceptor SNP Rs10774671). Alleles encoding nonprenylated OAS1 predominate except in people of African descent. Importantly, in hospitalized patients, expression of prenylated OAS1 was associated with protection from severe COVID-19, suggesting this antiviral defense is a major component of a protective antiviral response. Remarkably, approximately 55 million years ago, retrotransposition ablated the OAS1 prenylation signal in horseshoe bats (the presumed source of SARS-CoV-2). Thus, SARS-CoV-2 never had to adapt to evade this defense. As prenylated OAS1 is widespread in animals, the billions of people that lack a prenylated OAS1 could make humans particularly vulnerable to the spillover of coronaviruses from horseshoe bats.

Author list:


  1. MRC–University of Glasgow Centre for Virus Research, Institute of Infection, Inflammation and Immunity, University of Glasgow, UK
  2. Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, CB2 0AW, UK.
  3. Roslin Institute, University of Edinburgh, United Kingdom
  4. Laboratory of Tropical Diseases – Prof. Luiz Jacintho da Silva, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, SP, Brazil
  5. Department of Education and Research, Oncology Control Centre of Amazonas State – FCECON, Manaus, AM, Brazil; Tropical Medicine Foundation Dr. Heitor Vieira Dourado, Manaus, AM, Brazil
  6. Department of Pathology and Forensic Medicine, Tropical Medicine Foundation Dr. Heitor Vieira Dourado, Manaus, AM, Brazil
  7. ISARIC4C investigators
  8. Wellcome Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, UK
  9. Division of Infection & Immunity, Cardiff University, Cardiff, United Kingdom

# Corresponding author



Arthur Wickenhagen1, Elena Sugrue1*, Spyros Lytras1*, Srikeerthana Kuchi1*, Matthew L Turnbull1, Colin Loney1, Vanessa Herder1, Jay Allan1, Innes Jarmson1, Natalia Cameron-Ruiz1, Margus Varjak1, Rute M Pinto1, Douglas G Stewart1, Simon Swingler1, Marko Noerenberg1, Edward J D Greenwood2, Thomas W M Crozier2, Quan Gu1, Sara Clohisey3, Bo Wang3, Fabio Trindade Maranhão Costa4, Monique Freire Santana5, Luiz Carlos de Lima Ferreira6, ISARIC4C investigators7, Joao Luiz Da Silva Filho8, Matthias Marti8, Richard J Stanton9, Eddie C Y Wang9, Alfredo Castello-Palomares1, Antonia Ho1, Kenneth Baillie3,7, Ruth F Jarrett1, David L Robertson1, Massimo Palmarini1, Paul J Lehner2, Suzannah J Rihn1, Sam J Wilson1,#.