Analysis of Coronavirus Envelope Protein with Cellular Automata (CA) Model

TL;DR

This study uses cellular automata models to analyze how mutations in the coronavirus envelope protein influence its structure, function, and interaction with host cells, potentially affecting transmissibility.

Contribution

It introduces a novel computational cellular automata model to compare wild and mutant envelope proteins of SARS-CoV-2 and other coronaviruses, linking mutations to structural and functional differences.

Findings

Mutations in envelope protein correlate with changes in structure and function.

The model distinguishes differences between wild and mutant proteins.

Mutational impacts on transmissibility are inferred from structural analysis.

Abstract

The reason of significantly higher transmissibility of SARS Covid (2019 CoV-2) compared to SARS Covid (2003 CoV) and MERS Covid (2012 MERS) can be attributed to mutations reported in structural proteins, and the role played by non-structural proteins (nsps) and accessory proteins (ORFs) for viral replication, assembly, and shedding. Envelope protein E is one of the four structural proteins of minimum length. Recent studies have confirmed critical role played by the envelope protein in the viral life cycle including assembly of virion exported from infected cell for its transmission. However, the determinants of the highly complex viral - host interactions of envelope protein, particularly with host Golgi complex, have not been adequately characterized. CoV-2 and CoV Envelope proteins of length 75 and 76 amino acids differ in four amino acid locations. The additional amino acid Gly (G) at location 70 makes CoV length 76. The amino acid pair EG at location 69-70 of CoV in place of amino acid R in location 69 of CoV-2, has been identified as a major determining factor in the current investigation. This paper concentrates on the design of computational model to compare the structure/function of wild and mutants of CoV-2 with wild and mutants of CoV in the functionally important region of the protein chain pair. We hypothesize that differences of CAML model parameter of CoV-2 and CoV characterize the deviation in structure and function of envelope proteins in respect of interaction of virus with host Golgi complex; and this difference gets reflected in the difference of their transmissibility. The hypothesis has been validated from single point mutational study on- (i) human HBB beta-globin hemoglobin protein associated with sickle cell anemia, (ii) mutants of envelope protein of Covid-2 infected patients reported in recent publications.