No abstract

Since most anti-HIV-1 drugs must penetrate host cells to prevent viral replication, developing viral inhibitors as drugs is essential because they inactivate viruses before binding to host cells. gp120 HIV-1 surface glycoprotein, which has a role in the first stages of HIV-1 infection and entrance of the virus to the cell, is one of the proper molecules for targeted therapy. The phenylalanine-43 cavity located protectively between the inner and outer domains of gp120 of several virus variants has been an attractive medical target for its interaction with CD4. Contrary to industrial drugs, saffron's bioactivity has recently been noticed due to its bio-accessibility and bioavailability, low toxicity, and ease of production. Due to its carotenoid content, this study examined, for the first time, the main components of saffron (Crocin, Picrocrocin, Safranal and Crocetin) for their ability to inhibit viral-cellular membrane fusion and inactivate cell-free HIV-1.The dockings were performed using Autodock Vina Software to study the interactions between the saffron compounds mentioned above with gp120 and CD4 separately. Hence, the dockings were done using Autodock Vina software. The results showed that Crocin and Picrocrocin compounds attach to the protected Phe43 Cavity and Asp368, Trp427, and Ile371 (binding site) of gp120. To confirm the stability, the best complexes of docking were studied using molecular dynamic simulation (via Gromacs 2020.2). It was observed that Crocin keeps its attachment for 100 ns of the simulation, but Picrocrocin detaches. In the end, the binding affinity of Crocin and gp120 was calculated in the 100 snapshots of the last 10 ns of simulations using PRODIGY, which was À 10.3 kcal/mol. Finally, Crocin was suggested as a treatment for AIDS. Based on our atomic-level studies, we have determined that Crocin can stably bind to gp120 but not to human CD4 + T cells in the absence of HIV-1.