Structural Protein Mutation Landscape of SARS-CoV-2 in Goa, India (2020–2025): Nucleocapsid, Envelope, and Membrane Protein Analysis

This is the first nucleocapsid (N), envelope (E), and membrane (M) protein mutation analysis for SARS-CoV-2 in Goa, India, using 495 good-quality Nextclade-analysed sequences (GISAID EpiCoV; EPI_SET_260610gh; 2020–2025). N protein: 70 unique mutations; N:R203K (65.9%), N:G204R (65.5%), and N:P13L (64.8%) co-occur in approximately two-thirds of sequences with direct implications for rapid antigen test (RAT) diagnostic sensitivity in the Omicron era. Convergent evolution at N:R203 is documented — R203K in Alpha/Omicron and R203M in Delta/Kappa represent independent solutions at the same residue. E protein: E:T9I (64.8%) falls directly in the transmembrane viroporin channel (aa 8–38) and is the Omicron-defining E protein mutation; E:T11A (33.3%) creates a double viroporin channel mutation specifically in BA.2.75/Centaurus sequences. M protein: M:A63T (63.8%) and M:Q19E (63.4%) define the Omicron-era M protein architecture. N protein T cell epitope disruption was highest in Omicron sequences, concentrated in the diagnostically significant linker region. This paper constitutes Paper 4 of a comparative genomic surveillance series for the West Coast and Western Ghats corridor of India. Paper 1: https://doi.org/10.5281/zenodo.20632518. Paper 2: https://doi.org/10.5281/zenodo.20647945. Paper 3: https://doi.org/10.5281/zenodo.20676428. We gratefully acknowledge all data contributors, i.e., the Authors and their Originating laboratories responsible for obtaining the specimens, and their Submitting laboratories for generating the genetic sequence and metadata and sharing via the GISAID Initiative, on which this research is based. The GISAID Supplemental Table listing all originating and submitting laboratory data contributors is deposited with Paper 1 of this series (https://doi.org/10.5281/zenodo.20632518). GISAID citations: Elbe and Buckland-Merrett (2017) doi:10.1002/gch2.1018; Shu and McCauley (2017) doi:10.2807/1560-7917.ES.2017.22.13.30494; Khare et al. (2021) doi:10.46234/ccdcw2021.255