The binding affinity of the antiviral pentapeptide ATN-161 with the targets of the alpha5beta1 integrin closed and open conformations, the main protease and the omicron variant S (B.1.1.529) protein complexed with hACE2 of SARSCoV-2 was studied using molecular docking and molecular dynamics simulation. The complexes were successfully formed through the use of molecular docking simulations, in which binding poses of ATN-161 with the studied targets were obtained. Subsequently, classical molecular dynamics simulations were performed to investigate the stability of the formed complex. Steered molecular dynamics simulations, umbrella sampling and weighted histogram analysis method were used to obtain the mean force potential of each system, and thus calculate the binding energy for ATN-161 in the binding site of the respective protein targets. The results shows that ATN-161 binds to alpha5beta1 integrin in its active and inactive form, with binding energies of -14.4 plus–minus 0.5 and -12.6 plus–minus 0.2 kcal mol-1 , respectively. ATN-161 binds weakly to omicron variant protein S complexed with hACE2 with an energy of only -3.2 plus–minus 0.3 kcal mol-1. However, ATN-161 binds to MPRO with the binding energy of -17.7 plus–minus 0.2 kcal mol-1, indicating that this peptide binds strongly to MPRO. Finally, the study of the binding kinetics with the tau-RAMD method indicates that ATN-161 presents the relative residence time of 2.8 plus–minus 0.4 and 2.5 plus–minus 0.5 ns for ATN-161 and GC376, respectively. The results obtained in this work indicate a potential drug candidate against SARS-CoV-2, especially with the emergence of new variants of SARS-CoV-2.