tetano
Editor, Senior Moderator
Gene Rep
. 2021 Mar;22:100997.
doi: 10.1016/j.genrep.2020.100997. Epub 2020 Dec 8.
Mutational insights into the envelope protein of SARS-CoV-2
M Shaminur Rahman[SUP] 1 [/SUP], M Nazmul Hoque[SUP] 1 2 [/SUP], M Rafiul Islam[SUP] 1 [/SUP], Israt Islam[SUP] 1 [/SUP], Israt Dilruba Mishu[SUP] 1 [/SUP], Md Mizanur Rahaman[SUP] 1 [/SUP], Munawar Sultana[SUP] 1 [/SUP], M Anwar Hossain[SUP] 1 [/SUP]
Affiliations
Abstract
The ongoing mutations in the structural proteins of SARS-CoV-2 are the major impediment for prevention and control of the COVID-19 disease. Presently we focused on evolution of the envelope (E) protein, one of the most enigmatic and less studied protein among the four structural proteins (S, E, M and N) associated with multitude of immunopathological functions of SARS-CoV-2. In the present study, we comprehensively analyzed 81,818 high quality E protein sequences of SARS-CoV-2 globally available in the GISAID database as of 20 August 2020. Compared to Wuhan reference strain, our mutational analysis explored only 1.2 % (982/81818) mutant strains undergoing a total of 115 unique amino acid (aa) substitutions in the E protein, highlighting the fact that most (98.8 %) of the E protein of SARS-CoV-2 strains are highly conserved. Moreover, we found 58.77 % (134 of 228) nucleotides (nt) positions of SARS-CoV-2 E gene encountering a total of 176 unique nt-level mutations globally, which may affect the efficacy of real time RT-PCR-based molecular detection of COVID-19. Importantly, higher aa variations observed in the C-terminal domain (CTD) of the E protein, particularly at Ser[SUP]55[/SUP]-Phe[SUP]56[/SUP], Arg[SUP]69[/SUP] and the C-terminal end (DLLV: 72-75) may alter the binding of SARS-CoV-2 Envelope protein to tight junction-associated PALS1 and thus could play a key role in COVID-19 pathogenesis. Furthermore, this study revealed the V25A mutation in the transmembrane domain which is a key factor for the homopentameric conformation of E protein. Our analysis also observed a triple cysteine motif harboring mutation (L39M, A41S, A41V, C43F, C43R, C43S, C44Y, N45R) which may hinder the binding of E protein with spike glycoprotein. These results therefore suggest the continuous monitoring of the structural proteins including the envelope protein of SARS-CoV-2 since the number of genome sequences from across the world are continuously increasing.
Keywords: CTD, C-terminal domain; E, envelope; Envelope protein; M, membrane; Mutations; N, nucleocapsid; NC, negatively charged; NP, non-polar; PC, positively charged; S, spike; SARS-CoV-2; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus-2; TMD, transmembrane domain; Transmembrane domain; Triple cysteine motif; aa, amino acid; nt, nucleotide.
. 2021 Mar;22:100997.
doi: 10.1016/j.genrep.2020.100997. Epub 2020 Dec 8.
Mutational insights into the envelope protein of SARS-CoV-2
M Shaminur Rahman[SUP] 1 [/SUP], M Nazmul Hoque[SUP] 1 2 [/SUP], M Rafiul Islam[SUP] 1 [/SUP], Israt Islam[SUP] 1 [/SUP], Israt Dilruba Mishu[SUP] 1 [/SUP], Md Mizanur Rahaman[SUP] 1 [/SUP], Munawar Sultana[SUP] 1 [/SUP], M Anwar Hossain[SUP] 1 [/SUP]
Affiliations
- PMID: 33319124
- PMCID: PMC7723457
- DOI: 10.1016/j.genrep.2020.100997
Abstract
The ongoing mutations in the structural proteins of SARS-CoV-2 are the major impediment for prevention and control of the COVID-19 disease. Presently we focused on evolution of the envelope (E) protein, one of the most enigmatic and less studied protein among the four structural proteins (S, E, M and N) associated with multitude of immunopathological functions of SARS-CoV-2. In the present study, we comprehensively analyzed 81,818 high quality E protein sequences of SARS-CoV-2 globally available in the GISAID database as of 20 August 2020. Compared to Wuhan reference strain, our mutational analysis explored only 1.2 % (982/81818) mutant strains undergoing a total of 115 unique amino acid (aa) substitutions in the E protein, highlighting the fact that most (98.8 %) of the E protein of SARS-CoV-2 strains are highly conserved. Moreover, we found 58.77 % (134 of 228) nucleotides (nt) positions of SARS-CoV-2 E gene encountering a total of 176 unique nt-level mutations globally, which may affect the efficacy of real time RT-PCR-based molecular detection of COVID-19. Importantly, higher aa variations observed in the C-terminal domain (CTD) of the E protein, particularly at Ser[SUP]55[/SUP]-Phe[SUP]56[/SUP], Arg[SUP]69[/SUP] and the C-terminal end (DLLV: 72-75) may alter the binding of SARS-CoV-2 Envelope protein to tight junction-associated PALS1 and thus could play a key role in COVID-19 pathogenesis. Furthermore, this study revealed the V25A mutation in the transmembrane domain which is a key factor for the homopentameric conformation of E protein. Our analysis also observed a triple cysteine motif harboring mutation (L39M, A41S, A41V, C43F, C43R, C43S, C44Y, N45R) which may hinder the binding of E protein with spike glycoprotein. These results therefore suggest the continuous monitoring of the structural proteins including the envelope protein of SARS-CoV-2 since the number of genome sequences from across the world are continuously increasing.
Keywords: CTD, C-terminal domain; E, envelope; Envelope protein; M, membrane; Mutations; N, nucleocapsid; NC, negatively charged; NP, non-polar; PC, positively charged; S, spike; SARS-CoV-2; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus-2; TMD, transmembrane domain; Transmembrane domain; Triple cysteine motif; aa, amino acid; nt, nucleotide.