A full-length cDNA clone of SARS-CoV-2.

National Institute Of Allergy And Infectious Diseases

Investigators

Abstract

To achieve our goal, we generated a full-length infectious cDNA clone of SARS-CoV-2 coronavirus (isolate 2019-nCoV/USA_WA1/2020) and modified it for mouse model by introducing mouse-adapted mutations. In addition, using this cDNA we generated infectious clones for the three epidemiologically-significant variants of SARS-CoV-2: (1) UK variant (lineage B.1.1.7) was constructed by introducing 23 mutations into 2019-nCoV/USA_WA1/2020; (2) South African variant (lineage B.1.351) was constructed by introducing 21 mutations; (3) Brazilian/Manaus variant (lineage P.1) was constructed by introducing 24 mutations. To delineate the role of specific S-gene mutations in emergence of novel SARS-CoV-2 variants, we generated a panel of chimeric SARS-CoV-2 virus constructs. For that, mutations identified in the S gene of B.1.1.7, B.1.351, P.1 lineages were introduced into the genetic backbone of SARS-CoV-2 cDNA (isolate 2019-nCoV/USA_WA1/2020). Recovery and characterization of recombinant viruses in cell culture and/or in mouse model have been performed or are currently on-going in the laboratories of Dr. D. R. Smith (Naval Medical Research Center, Fort Frederick) and Dr. S. Best, (Rocky Mountain National Laboratories, NIAID).