The worldwide impact of viral diseases throughout history is substantial. Our research focus was SARS-CoV-2, which emerged as a substantial problem for the scientific community. Given the limitations of current therapies in terms of efficacy and availability, it is imperative to develop safe and effective inhibitors that interface between the virus and the ACE2 receptor. This study aims to synthesize peptides as ACE2 inhibitors and evaluate their efficacy in preventingSARS-CoV-2 infection via an a5ß1 integrin-based mechanism. ATN-161 has shown high specificity and efficacy against SARS-CoV-2, demonstrating safety in both in vivo and in vitro studies. Based on the reported ATN-161 structure, three peptide analogs were designed by strategically modifying the position of the proline in the amino acid sequence. The ability of proline to stabilize and enhance peptide activity was exploited to improve the analog properties. The synthesis of ATN-161 analogs was accomplished using solid-phase peptide synthesis (SPPS). The stepwise addition of protected amino acids to the growing peptide chain involved affixing, de protection, amino acid coupling, and cleavage of the synthesized peptide from the resin. To assess their potential as anti-Covid agents, the peptides were evaluated on Vero (E6) cells. Experimental results demonstrated that one of the synthesized analogs reduced the virus-receptor interaction more effectively than ATN-161, demonstrating its role in mitigatingSARS-CoV-2 infection. This is the first study reporting the potential therapeutic efficacy of synthetic analogs of ATN-161 as fusion inhibitors.