key: cord-1051884-zdx77tfv
authors: Rosenthal, Sun Hee; Kagan, Ron M.; Gerasimova, Anna; Anderson, Ben; Grover, David; Hua, Michael; Liu, Yan; Owen, Renius; Lacbawan, Felicitas
title: Identification of eight SARS-CoV-2 ORF7a deletion variants in 2,726 clinical specimens
date: 2020-12-11
journal: bioRxiv
DOI: 10.1101/2020.12.10.418855
sha: a2fb0de8683a1299699ac5aeb92afc5053585ef9
doc_id: 1051884
cord_uid: zdx77tfv

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ORF7a, the ortholog of SARS-CoV ORF7a, is a type I transmembrane protein and plays an important role in virus-host interactions. Deletion variants in ORF7a may influence virulence, but only a few such isolates have been reported. Here, we report 8 unique ORF7a deletion variants of 6 to 96 nucleotides in length identified from 2,726 clinical specimens collected in March of 2020.

Although Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes are 19 considered genetically stable, various mutations within the genome have been reported [1] . 20 SARS-CoV-2 ORF7a, the ortholog of SARS-CoV ORF7a, is a type I transmembrane protein and 21 plays an important role in virus-host interactions [2, 3] . Deletion variants in ORF7a may 22 influence virulence, but only a few such isolates have been reported [4] [5] [6] . 23 As part of an ongoing SPHERES Consortium project [7] , we sequenced the SARS-CoV- Figure 1A ). The 13-nucleotide deletion removed the ORF7a stop 43 codon and the ORF7b start codon, resulting in an extended ORF7a and a truncated ORF7b. is 427bp, and the expected amplicon sizes of the deletion isolates of 96, 57, 40, 18, 13, 12, 9, and 56 6nt_del are 331, 370, 387, 409, 414, 415, 418 , and 421bp, respectively. All deletion variants were confirmed by Sanger sequencing using amplicons targeting the 59 ORF7a-ORF7b regions ( Figure 1B) . Three of the 8 isolates were heterogenous, with deletion 60 variant frequency between 18% and 38% as determined by next-generation sequencing (NGS) 61 ( βF, and βG) β-sheet in the ectodomain was suggested to be the major functional interface [10] .

As the 4 ectodomain deletion variants in our study resulted in the loss of at least 1 β-sheet strand 69 within the functional interface, we hypothesize that those isolates would have lost ORF7a 

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