While advances in vaccine technology allowed the rapid production and approval of COVID-19 vaccines, the availability of antivirals has relied mainly on drug repurposing. Most of the proposed antivirals aim to inhibit viral entry or regulate the severity of the coronavirus infection. Of the SARS-CoV-2 three structural proteins (membrane, envelope, and nucleocapsid) that play an essential role in the assembly and formation of infectious virion particles, the envelope protein (E protein) is the least studied in terms of finding inhibitors of its function using repurposed drugs. E protein can homo-oligomerize to form a pentamer that functions as a cation-selective ion channel. This study aimed to find potential antiviral molecules targeting SARS-CoV-2 viroporin E. To achieve this, we applied virtual screening methods to the ASINEX antiviral library that contains 6827 compounds. Eight promising inhibitors were identified. The docking process was conducted on a structure of the SARS-CoV-2 viroporin E (2-E) taken from the NMR-resolved structure published by Cao Y. et al. [5], showing that these compounds could accommodate within the 2-E channel through aliphatic, aromatic, and polar interactions with the amino acid residues Val18, Leu20, Phe16, Phe19, and Thr23 of helices B, D, and E of the pentamer. All these compounds showed excellent ADMET properties like absorption, metabolism, minimal toxicity, and bioavailability. They remained stabilized at the binding site of viroporin E during the MD simulation and confirmed by MMPBSA results. The identified lead compounds are proposed as effective inhibitors of the 2-E by inhibiting the envelope formation and virion assembly.