Many conotoxins, natural peptides of marine cone snails, have been identified to target neurons. Here, we provide data on pharmacological families of the conotoxins of 11 species of cone snails collected in Bali. The identified definitive pharmacological families possibly targeting neuronal tissues were α (alpha), ι (iota), κ (kappa), and ρ (rho). These classes shall target nicotinic acetylcholine receptors, voltage-gated Na channels, voltage-gated K channels, and α1-adrenoceptors, respectively. The VI/VII-O3 conotoxins might be prospected as an inhibitor of N-methyl-d-aspartate. Con-ikot-ikot could be applied as an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor blocker medicine. The definitive pharmacology classes of conotoxins as well as those yet to be elucidated need to be further established and verified.
The prolonged global spread and community transmission of severe acute respiratory syndrome virus 2 (SARS-CoV-2) has led to the emergence of variants and brought questions regarding disease severity and vaccine effectiveness. We conducted simple bioinformatics on the spike gene of a representative of each variant. The data show that a number of polymorphic amino acids are located mostly on the amino-terminal side of the S1/S2 cleavage site. The Omicron variant diverges from the others, with the highest number of amino acid substitutions, including the receptor-binding site (RBS), epitopes, S1/S2 cleavage site, fusion peptide, and heptad repeat 1. The current sharp global increase in the frequency of the Omicron genome constitutes evidence of its high community transmissibility. In conclusion, the proposed guideline could give an immediate insight of the probable biological nature of any variant of SARS-Cov-2. As the Omicron diverged the farthest from the original pandemic strain, Wuhan-Hu-1, we expect different epidemiological and clinical patterns of Omicron cases. On vaccine efficacy, slight changes in some epitopes while others are conserved should not lead to a significant reduction in the effectiveness of an approved vaccine.
Since its discovery at the end of 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly evolved into many variants, including the subvariant BA.2 and the GKA clade. Genomic clarification is needed for better management of the current pandemic as well as the possible reemergence of novel variants. The sequence of the reference genome Wuhan-Hu-1 and approximately 20 representatives of each variant were downloaded from GenBank and GISAID. Two representatives with no track of in-definitive nucleotides were selected. The sequences were aligned using muscle. The location of insertion/deletion (indel) in the genome was mapped following the open reading frame (ORF) of Wuhan-Hu-1. The phylogeny of the spike protein coding region was constructed using the maximum likelihood method. Amino acid substitutions in all ORFs were analyzed separately. There are two indel sites in ORF1AB, eight in spike, and one each in ORF3A, matrix (MA), nucleoprotein (NP), and the 3′-untranslated regions (3′UTR). Some indel sites and residues/substitutions are not unique, and some are variant-specific. The phylogeny shows that Omicron, Deltacron, and BA2 are clustered together and separated from other variants with 100% bootstrap support. In conclusion, whole-genome comparison of representatives of all variants revealed indel patterns that are specific to SARS-CoV-2 variants or subvariants. Polymorphic amino acid comparison across all coding regions also showed amino acid residues shared by specific groups of variants. Finally, the higher transmissibility of BA.2 might be due at least in part to the 48 nucleotide deletions in the 3′UTR, while the seem-to-be extinction of GKA clade is due to the lack of genetic advantages as a consequence of amino acid substitutions in various genes.
Since its discovery at the end of 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly evolved into many variants, including subvariant BA.2 and the GKA clade. Genomic clarification is needed for better management of the current pandemic as well as the possible re-emergence of novel variants. The sequence of the original strain Wuhan-Hu-1 and approximately 20 representatives of each variant were downloaded from GenBank and GISAID. Two representatives with no track of un-definitive nucleotides were selected. The sequences were aligned using Muscle. The location of insertion/deletion (indel) in the genome was mapped following the open reading frame (ORF) of Wuhan-Hu-1. Amino acid substitutions in all ORFs were analysed separately. Evolutionary analysis was inferred using maximum likelihood. There are two indel sites in ORF1AB, eight in spike, and one each in ORF3A, Matrix (MA), Nucleoprotein (NP), and the 3’-untranslated regions (3’UTR). Some indel sites are not unique, and some are variant specific. There are 10 residues shared by the Omicron, BA2, and GKA lineages. Three deletions in NP are unique to Omicron and BA.2; two substitutions in ORF1AB, four in spike, three in NP, and two in ORF7A and ORF8 were exclusive to the Delta and GPA clades. Delta, Omicron, and BA.2 share the same single residue spike. Three insertions in spike are unique for Omicron and GKA. Phylogenetic analysis shows that the Omicron, BA.2, and GKA clades share a common cluster that emerged from Delta. In conclusion, whole-genome comparison reveals indels and polymorphic amino acids specific to variants or sub-variants. We propose that the GKA clade is an Omicron subvariant. Finally, the higher transmissibility of BA.2 might be attributed to a 48-nucleotide deletion in the 3’UTR.
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