SARS-Cov-2 ORF3a: Mutability and function

Martina Bianchi,Alessandra Borsetti,Massimo Ciccozzi,Stefano Pascarella

doi:10.1016/j.ijbiomac.2020.12.142

Martina Bianchi, Alessandra Borsetti + Show 2 more

Open Access

https://doi.org/10.1016/j.ijbiomac.2020.12.142

Copy DOI

Abstract

In this study, analysis of changes of SARS-CoV-2 ORF3a protein during pandemic is reported. ORF3a, a conserved coronavirus protein, is involved in virus replication and release. A set of 70,752 high-quality SARS-CoV-2 genomes available in GISAID databank at the end of August 2020 have been scanned. 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.

Highlights

Coronavirus Disease (COVID-19) became almost suddenly, but not unexpectedly, a serious threat to human health [1,2,3]
The etiological agent of the disease is a Coronavirus classified as Sars-CoV-2 (Severe acute respiratory syndrome CoronaVirus 2) related to Sars-CoV
A software workflow able to carry out a quick, systematic and repeatable screening of the Sars-CoV-2 genome isolates to scrutinize the frequency of specific mutations in each of the protein expressed by the virus, is reported

Summary

Introduction

Coronavirus Disease (COVID-19) became almost suddenly, but not unexpectedly, a serious threat to human health [1,2,3]. In 2002, Sars-CoV caused an outbreak of atypical and severe, often lethal, pneumonia in Guangdong province, China This virus had a relatively low contagiousness and could be contained as to prevent worldwide spreading [4]. Many initiatives are currently ongoing to develop effective diagnostic tools, vaccines and therapeutic strategies able to prevent and fight Sars-CoV-2 infections and diseases. In this context, it is important to understand the dynamics of evolution of the virus and to study how its proteome changes. A software workflow able to carry out a quick, systematic and repeatable screening of the Sars-CoV-2 genome isolates to scrutinize the frequency of specific mutations in each of the protein expressed by the virus, is reported. The most pervasive mutations of the three proteins are described and the most variable/conservative regions mapped onto the sequences

Methods

Results

Conclusion