Long COVID-19: Electronic Characterization of the SARS-CoV-2 Envelope Protein Using DFT as a Basis for Therapeutic Hypothesis

Long COVID, or post-COVID-19, is emerging as a prevalent and complex syndrome affecting a significant percentage of patients who have recovered from the acute phase of SARS-CoV-2 infection. The viral envelope protein (E), a 75 amino acid ion channel, is a crucial structural component involved in viral pathogenesis. This study employs density functional theory (DFT) principles to calculate global reactivity descriptors of the short hydrophilic N-terminal domain of the E protein. The results indicate an ionization potential (<i>IP</i>) of 6.47eV, an electron affinity (<i>EA</i>) of 4.39eV, and a molecular hardness (<i>η</i>) of 1.04eV, suggesting moderate to high chemical reactivity. An electrophilicity (<i>ω</i>) value of 14.17eV reveals a marked tendency to accept electrons. These electronic descriptors, along with the described biological functions of the E protein, such as its role in viral assembly, budding, and modulation of the host inflammatory response, position it as a promising therapeutic target. We also report on the reactivity sites (<i>HOMO-LUMO</i>) present in the short hydrophilic N-terminal domain. Inhibition of the E protein could alter key viral processes and attenuate the immune dysregulation underlying persistent COVID-19, opening new avenues for rational drug design.