Working Paper Article Version 2 This version is not peer-reviewed

SARS-Cov-2 ORF3a: Mutability and Function

Version 1 : Received: 3 July 2020 / Approved: 5 July 2020 / Online: 5 July 2020 (06:54:01 CEST)
Version 2 : Received: 29 October 2020 / Approved: 30 October 2020 / Online: 30 October 2020 (10:10:58 CET)

How to cite: Bianchi, M.; Borsetti, A.; Ciccozzi, M.; Pascarella, S. SARS-Cov-2 ORF3a: Mutability and Function. Preprints 2020, 2020070049 Bianchi, M.; Borsetti, A.; Ciccozzi, M.; Pascarella, S. SARS-Cov-2 ORF3a: Mutability and Function. Preprints 2020, 2020070049


In this study, the analysis of the changes of SARS-CoV-2 Orf3a protein during pandemic is reported. Orf3a, a conserved protein in the Coronaviruses, is involved in virus replication and release. A software workflow able to carry out a quick, systematic and repeatable screening of the SARS-CoV-2 genome isolates to detect protein mutations, was utilized to scan 70,752 high-quality SARS-CoV-2 genomes available in GISAID databank at the end of August 2020. All ORF3a mutations in the virus genomes were grouped according to the collection date interval and over the entire data set. The considered intervals were start of collection-February, March, April, May, June, July and August 2020. The top five most frequent variants were examined within each collection interval. Overall, seventeen variants have been isolated. Ten of the seventeen mutant sites occur within the transmembrane (TM) domain of ORF3a and are in contact with the central pore or side tunnels. The other variant sites are in different places of the Orf3a structure. Within the entire sample, the five most frequent mutations are V13L, Q57H, Q57H+A99V, G196V and G252V. The same analysis identified 28 sites identically conserved in all the genome isolates. These sites are possibly involved in stabilization of monomer, dimer, tetramerization and interaction with other cellular components. The results here reported can be helpful to understand virus biology and to design new therapeutic strategies.

Subject Areas

Orf3a; Tunnel; Conserved sites; Q57H; Viroporin; Mutated sites

Comments (1)

Comment 1
Received: 30 October 2020
Commenter: Stefano Pascarella
Commenter's Conflict of Interests: Author
Comment: This manuscript is a "specialization" of the overview reported in the parent preprint. In fact, it focusses onto the protein ORF3a while applying the same methodology. Authorship has been changed to reflect the new contributions to the paper. The preprint has been submitted to a journal.
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