Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jul 15:300:198441.
doi: 10.1016/j.virusres.2021.198441. Epub 2021 Apr 30.

Pathogenic perspective of missense mutations of ORF3a protein of SARS-CoV-2

Sk Sarif Hassan  1 , Diksha Attrish  2 , Shinjini Ghosh  3 , Pabitra Pal Choudhury  4 , Bidyut Roy  5
Affiliations

Pathogenic perspective of missense mutations of ORF3a protein of SARS-CoV-2

Sk Sarif Hassan et al. Virus Res. .

Abstract

One of the most important proteins for COVID-19 pathogenesis in SARS-CoV-2 is the ORF3a which is the largest accessory protein among others coded by the SARS-CoV-2 genome. The major roles of the protein include virulence, infectivity, ion channel activity, morphogenesis, and virus release. The coronavirus, SARS-CoV-2 is mutating rapidly, therefore, critical study of mutations in ORF3a is certainly important from the pathogenic perspective. Here, a sum of 175 non-synonymous mutations in the ORF3a of SARS-CoV-2 were identified from 7194 complete genomes of SARS-CoV-2 available from NCBI database. Effects of these mutations on structural stability, and functions of ORF3a were also studied. Broadly, three different classes of mutations, such as neutral, disease, and mixed (neutral and disease) types of mutations were observed. Consecutive phenomena of mutations in ORF3a protein were studied based on the timeline of detection of the mutations. Considering the amino acid compositions of the ORF3a protein, twenty clusters were detected using the K-means clustering method. The present findings on 175 novel mutations of ORF3a proteins will extend our knowledge on ORF3a, a vital accessory protein in SARS-CoV-2, to enlighten the pathogenicity of this life-threatening virus.

Keywords: COVID-19; Genetic variations; Missense mutations; ORF3a; SARS-CoV-2; Shannon entropy.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Schematic view of the domains in primary sequence of ORF3a protein.
Fig. 2
Fig. 2
Mutations in the respective position in ORF3a protein sequence compared with reference Wuhan sequence YP_009724391.1. Note: From: existing amino acid in reference sequence; position: amino acid position in the sequence; To: mutated amino acid in studied sequence.
Fig. 3
Fig. 3
Pie chart of the frequency of distinct mutations.
Fig. 4
Fig. 4
A snapshot of the predicted effect of the frequently occurred mutation Q57H in ORF3a using Meta-SNP web-server.
Fig. 5
Fig. 5
Percentage of disease, neutral, and mixed (neutral & disease) type of mutations over the ORF3a proteins.
Fig. 6
Fig. 6
World maps of percentage of occurrence of neutral, disease, and mixed type of mutations over the ORF3a proteins.
Fig. 7
Fig. 7
Flow of mutations in Australian ORF3a proteins.
Fig. 8
Fig. 8
Flow of mutations in ORF3a proteins from the USA.
Fig. 9
Fig. 9
Flow of mutations in ORF3a proteins of Indian origin.
Fig. 10
Fig. 10
Network flow of mutations of ORF3a proteins considering from various geo-locations.
Fig. 11
Fig. 11
Network flow of mutations of ORF3a proteins considering from various geo-locations. Note: A: Australia, B: Bangaldesh, F: France, G: Greece, and U: USA.
Fig. 12
Fig. 12
Structures of ORF3a (Reference coloured as grey in left), Structure of mutated ORF3a (coloured with blue in the middle), and Overlaid ORF3a (rightmost image).
Fig. 13
Fig. 13
Structures of ORF3a (Reference coloured as grey in left), Structure of mutated ORF3a (coloured with blue in the middle), and Overlaid ORF3a (rightmost image).
Fig. 14
Fig. 14
Structures of ORF3a  (Reference coloured as grey in left), Structure of mutated ORF3a (coloured with blue in the middle), and Overlaid ORF3a (rightmost image).
Fig. 15
Fig. 15
Structures of ORF3a (Reference coloured as grey in left), Structure of mutated ORF3a  (coloured with blue in the middle), and Overlaid ORF3a (rightmost image).
Fig. 16
Fig. 16
Structures of ORF3a (Reference coloured as grey in left), Structure of mutated ORF3a (coloured with blue in the middle), and Overlaid ORF3a  (rightmost image).
Fig. 17
Fig. 17
Dendogram of the twenty clusters.
Fig. 18
Fig. 18
SE of amino acid compositions of ORF3a proteins.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Al-Osail A.M., Al-Wazzah M.J. The history and epidemiology of middle east respiratory syndrome corona virus. Multidiscip. Respir. Med. 2017;12(1):20. - PMC - PubMed
    1. Andersen K.G., Rambaut A., Lipkin W.I., Holmes E.C., Garry R.F. The proximal origin of sars-cov-2. Nat. Med. 2020;26(4):450–452. - PMC - PubMed
    1. Brooks D.J., Fresco J.R., Lesk A.M., Singh M. Evolution of amino acid frequencies in proteins over deep time: inferred order of introduction of amino acids into the genetic code. Mol. Biol. Evolut. 2002;19(10):1645–1655. - PubMed
    1. Buchholz U.J., Bukreyev A., Yang L., Lamirande E.W., Murphy B.R., Subbarao K., Collins P.L. Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity. Proc. Natl. Acad. Sci. USA. 2004;101(26):9804–9809. - PMC - PubMed
    1. Capriotti E., Fariselli P., Casadio R. I-mutant2. 0: predicting stability changes upon mutation from the protein sequence or structure. Nucleic Acids Res. 2005;33(suppl_2):W306–W310. - PMC - PubMed