Evolutionary Insights into the Envelope Protein of SARS-CoV-2

Abstract

The ongoing mutations in the structural proteins of SARS-CoV-2 is the major impediment for prevention and control of the COVID-19 disease. The envelope (E) protein of SARS-CoV-2 is a structural protein existing in both monomeric and homopentameric forms, associated with a multitude of functions including virus assembly, replication, dissemination, release of virions, infection, pathogenesis, and immune response stimulation. In the present study, 81,818 high quality E protein sequences retrieving from the GISAID were subjected to mutational analyses. Our analysis revealed that only 0.012 % (982/81818) stains possessed amino acid (aa) substitutions in 63 sites of the genome while 58.77% mutations in the primary structure of nucleotides in 134 sites. We found the V25A mutation in the transmembrane domain which is a key factor for the homopentameric conformation of E protein. We also observed a triple cysteine motif harboring mutations (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 each structural protein of SARS-CoV-2 since the number of genome sequences from across the world are continuously increasing.

Blockade of SARS-CoV-2 infection in vitro by highly potent PI3K-α/mTOR/BRD4 inhibitor

“…Several observations related to Gordon et al ( 29 ) reporting that BRD4 binds to the SARS-CoV-2 E protein include: 1) the E protein forms a homopentameric cation-selective channel which is required for viral budding and release from cells, 2) the E protein is a 72-residue viroporin molecule, 3) mutations or deletions within the transmembrane channel attenuate viral pathogenicity ( 53 ). Data from emerging mutant strains of SARS-CoV-2 strains indicates presence of several variation in the C terminal domain E protein, that may impact its binding with host protein PALS1with altered disease pathogenesis ( 54 ). BRD2/BRD4 also has a significant role in cell cycle regulation, inflammation, and inhibition of BRD4 by SF2523 enhances the innate and adaptive immune response ( 37 ).…”

The Effect of Neurotransmitters on Programmed Cell Death and Formation of Reactive Oxygen Species in the Epidermis of Pea Leaves

“…2, А, Б). В мировой литературе есть множество работ, свидетельствующих об антиоксидантных свойствах различных фенольных соединений [26][27][28]. Д.Б.…”

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“…Further, Saurabh and colleagues [19] We can infer that the tertiary structure of the E protein is the same in SARS-CoV-2 as in ZC45 and ZXC21, since the amino acid sequences are identical. Further, we can infer that all strains of SARS-CoV-2 that have developed since the outbreak have almost the same tertiary structure, since 98.8% of SARS-CoV-2 strains are highly conserved, with an extremely low mutation rate: 1.2% of SARS-CoV-2 strains had gene mutations (synonymous and nonsynonymous) from the Wuhan reference strain [22]. High levels of amino acid variation in the PBM (D72Y, D72G, D72H, D72N, D72V, and D72A; L73F, L73V; L74P, L74V; V75L, V75F) have been observed [22], and these may alter the binding of the SARS-CoV-2 E protein to ZO-1 and/or protein associated with LIN7 1 (PALS1) [22].…”

“…Further, we can infer that all strains of SARS-CoV-2 that have developed since the outbreak have almost the same tertiary structure, since 98.8% of SARS-CoV-2 strains are highly conserved, with an extremely low mutation rate: 1.2% of SARS-CoV-2 strains had gene mutations (synonymous and nonsynonymous) from the Wuhan reference strain [22]. High levels of amino acid variation in the PBM (D72Y, D72G, D72H, D72N, D72V, and D72A; L73F, L73V; L74P, L74V; V75L, V75F) have been observed [22], and these may alter the binding of the SARS-CoV-2 E protein to ZO-1 and/or protein associated with LIN7 1 (PALS1) [22]. Except for the V25A mutation in the transmembrane domain [22], most of the mutations do not affect the tertiary structure with respect to the homopentameric cation channel viroporin.…”

“…High levels of amino acid variation in the PBM (D72Y, D72G, D72H, D72N, D72V, and D72A; L73F, L73V; L74P, L74V; V75L, V75F) have been observed [22], and these may alter the binding of the SARS-CoV-2 E protein to ZO-1 and/or protein associated with LIN7 1 (PALS1) [22]. Except for the V25A mutation in the transmembrane domain [22], most of the mutations do not affect the tertiary structure with respect to the homopentameric cation channel viroporin. If SARS-CoV-2 accrues further mutations in areas that are currently not mutated, the tertiary structure will be altered, which would eventually lead to the malfunction of the E protein viroporin.…”