ABSTRACT
Objectives: To address a highly mutable pathogen, mutations must be evaluated. SARS-CoV-2 involves changing infectivity, mortality, and treatment and vaccination susceptibility resulting from mutations. Materials and Methods: We investigated the Asian and worldwide samples of amino-acid sequences (AASs) for envelope (E), membrane (M), nucleocapsid (N), and spike (S) proteins from the announcement of the new coronavirus 2019 (COVID-19) up to January 2022. Sequence alignment to the Wuhan-2019 virus permits tracking mutations in Asian and global samples. Furthermore, we explored the evolutionary tendencies of structural protein mutations and compared the results between Asia and the globe. Results: The mutation analyses indicated that 5.81%, 70.63%, 26.59%, and 3.36% of Asian S, E, M, and N samples did not display any mutation. Additionally, the most relative mutations among the S, E, M, and N AASs occurred in the regions of 508 to 635 AA, 7 to 14 AA, 66 to 88 AA, and 164 to 205 AA in both Asian and total samples. D614G, T9I, I82T, and R203M were inferred as the most frequent mutations in S, E, M, and N AASs. Timeline research showed that substitution mutation in the location of 614 among Asian and total S AASs was detected from January 2020. Conclusion: N protein was the most non-conserved protein, and the most prevalent mutations in S, E, M, and N AASs were D614G, T9I, I82T, and R203M. Screening structural protein mutations is a robust approach for developing drugs, vaccines, and more specific diagnostic tools.
ABSTRACT
BACKGROUND: Emergence of new variants mainly variants of concerns (VOC) is caused by mutations in main structural proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, we aimed to investigate the mutations among structural proteins of SARS-CoV-2 globally. METHODS: We analyzed samples of amino-acid sequences (AASs) for envelope (E), membrane (M), nucleocapsid (N), and spike (S) proteins from the declaration of the coronavirus 2019 (COVID-19) as pandemic to January 2022. The presence and location of mutations were then investigated by aligning the sequences to the reference sequence and categorizing them based on frequency and continent. Finally, the related human genes with the viral structural genes were discovered, and their interactions were reported. RESULTS: The results indicated that the most relative mutations among the E, M, N, and S AASs occurred in the regions of 7 to 14, 66 to 88, 164 to 205, and 508 to 635 AAs, respectively. The most frequent mutations in E, M, N, and S proteins were T9I, I82T, R203M/R203K, and D614G. D614G was the most frequent mutation in all six geographical areas. Following D614G, L18F, A222V, E484K, and N501Y, respectively, were ranked as the most frequent mutations in S protein globally. Besides, A-kinase Anchoring Protein 8 Like (AKAP8L) was shown as the linkage unit between M, E, and E cluster genes. CONCLUSION: Screening the structural protein mutations can help scientists introduce better drug and vaccine development strategies.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Mutation , Spike Glycoprotein, Coronavirus/genetics , Amino Acid Sequence , NucleocapsidABSTRACT
To understand SARS-CoV-2 microevolution, this study explored the genome-wide frequency, gene-wise distribution, and molecular nature of all point-mutations detected across its 71,703 RNA-genomes deposited in GISAID till 21 August 2020. Globally, nsp1/nsp2 and orf7a/orf3a were the most mutation-ridden non-structural and structural genes respectively. Phylogeny of 4618 spatiotemporally-representative genomes revealed that entities belonging to the early lineages are mostly spread over Asian countries, including India, whereas the recently-derived lineages are more globally distributed. Of the total 20,163 instances of polymorphism detected across global genomes, 12,594 and 7569 involved transitions and transversions, predominated by cytidine-to-uridine and guanosine-to-uridine conversions, respectively. Positive selection of nonsynonymous mutations (dN/dS >1) in most of the structural, but not the non-structural, genes indicated that SARS-CoV-2 has already harmonized its replication/transcription machineries with the host metabolism, while it is still redefining virulence/transmissibility strategies at the molecular level. Mechanistic bases and evolutionary/pathogenicity-related implications are discussed for the predominant mutation-types.