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This article is about Nature. We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply. The coronaviruses disease is especially severe in young people. The effectiveness of the vaccine is compromised by the emergence of the enhanced transmissibility variant. The need for further development of anti-SARS-CoV-2 therapies is emphasized by the emergence of these variant. We describe the isolation of highly virulent mouse-adapted viruses and use them to test a novel therapeutic drug in aged animals. Humans have many of the same genes that are found in mice, but they also have some of the same genes that are found in humans. Immune pressure is not required for selection according to their appearance during mouse adaptation. In aged mice, elevated levels of prostaglandin D2 and PLA 2 G2D contributed to poor outcomes. Middle-aged mice that lack expression of PLA 2 G2D are protected from severe disease. Treatment with a PTGDR antagonist, asapiprant, protected aged mice from lethal infections. The PLA 2 G2D-PGD 2 /PTGDR pathway is a useful target for therapeutic interventions because it protects aged animals. The strategy for identifying immune cells at 6dpi in BALB/c mice was used. You agree to abide by the Community Guidelines when you submit a comment. If you find something that does not comply with our guidelines, please flag it as inappropriate.
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