The latest research further strengthened that the spike-RBD sequence of SARS-CoV-2 interacts with host receptor ACE2 and this RBD-ACE2 complex plays a key role in virus invasion and virulence (Walls et al., 2020). Based on virtual screening results, LDN interacts with ACE2. Naltrexone prefers to bind in the central cavity formed SARS-CoV-2 RBD and ACE2 receptor. Tyr505 and Glu406 of RBD formed two crucial hydrogen bonds with the naltrexone with an atomic distance of 2.08 and 1.80, while, Arg403 formed electrostatic contact. While the His34, Glu37, and Phe390 of ACE2 displayed some hydrophobic contacts (mostly pi-alkyl contacts) with naltrexone. Overall this suggests LDN can strongly interact with SARS-CoV-2 RBD, including its RBM may further influence RDB- ACE2 binding, and host cell infectivity.