Helicobacter pylori infects approximately 44% of the global human population (over 3.5 billion individuals) and is classified as a Group I definite carcinogen by the WHO/IARC. Current antibiotic eradication therapies face critically escalating primary resistance: clarithromycin resistance exceeds 20-33% globally, metronidazole 35-70%, and levofloxacin 13-35%. Bacteriophage therapy represents a biologically rational alternative, but no naturally occurring H. pylori-specific phage capable of surviving the gastric environment (pH 2.0-3.5) has been isolated and no clinical trials exist. We present the first fully de novo computational pipeline for the design of a synthetic acid-resistant bacteriophage targeting H. pylori, developed within a local high-performance computing infrastructure. Using the Extremophile Capsid Engineering (ECE) protocol — inspired by hyperthermophilic archaea (Sulfolobus acidocaldarius, Picrophilus torridus) — we extracted the Major Capsid Protein (MCP) from a Campylobacter phage scaffold (NCBI: 294338166), applied 90 targeted mutagenic substitutions replacing acid-labile polar residues with hydrophobic amino acids (Val, Leu, Ile, Met, Trp), and introduced Cysteine disulfide bridges mimicking archaeal covalent cross-linking. The engineered MCP was folded via ESMFold tensorial prediction, energy-minimized to -845.2 kcal/mol (resolving 13 steric clashes), and assembled with 6 copies of a synthetic Receptor Binding Protein (RBP; 214 aa; energy: -467.8 kcal/mol) in hexagonal symmetry. The complete virion was rendered at 61 FPS via our proprietary Hardware-accelerated WebGL2 viewer (WebGL2 Raymarching + NGL dual-mode engine).
Г Л Снигур (Thu,) studied this question.