Modares Journal of Biotechnology

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), the causative agent of COVID-19, initiates its life cycle by binding to the angiotensin-converting enzyme 2 (ACE2) receptor. The viral spike protein facilitates this binding, enabling viral entry into host cells. Inhibiting ACE2 could therefore prevent viral entry and mitigate COVID-19 pathogenesis. To identify potential ACE2 inhibitors, we employed a combined computational approach involving pharmacophore modeling, molecular docking, and molecular dynamics simulations. A pharmacophore model was generated and used to screen the ZINC database. Subsequently, molecular docking studies were performed to assess the binding affinity of the selected compounds to the ACE2 active site. Six compounds with binding free energies below -11 kcal/mol and favorable binding orientations were identified as potential ACE2 inhibitors. Molecular dynamics simulations were conducted on the top-ranked compound, ZINC39880968, to validate the docking results. The simulation results were consistent with the docking predictions, further supporting the potential inhibitory activity of this compound. Overall, our findings suggest that ZINC39880968 is a promising candidate for further investigation as a potential therapeutic agent against COVID-19.

Abstract The COVID-19 pandemic has created a global health crisis, and developing effective treatments is essential to prevent the spread of the disease and save millions of lives. One of the key proteins involved in the replication cycle of SARS-CoV-2, the virus that causes COVID-19, is the main protease enzyme, 3CL^pro. Due to its high importance, this enzyme is the subject of molecular, structural, and clinical investigations, and efforts have been made to develop drugs that can inhibit its activity. One such drug is the chemical compound N3, which has been found to have a high inhibitory effect against 3CL^pro. However, traditional medicine perspectives on this issue have been less explored. In this research, molecular docking interaction simulation and all-atom molecular dynamics (MD) simulation were conducted to study the potential inhibitory capability of generally available 21 plant-extracted compounds against the 3CL^pro enzyme. Three compounds with the highest inhibition probability were selected from the molecular docking results and subjected to 100 ns of MD simulation to investigate their stability and structural-dynamic-energetic features. Beside the complexes stability, the results from the simulation demonstrated that, all our selected three compounds induce N3 comparable structural-dynamics characteristics to 3CL^pro and, therefore, are expected to have a similar inhibitory ability against this enzyme. Compound number 5 was found to have the most favorable binding energy and was proposed as the best plant substitute for N3. The results from this research can be directly used to design experimental research for 3CLpro enzyme inhibition, saving the time-financial cost.

Abstract Abstract
Aims: Basillus anthrasis is the causative agent of anthrax that can form the highly resilient spore. Because of this attribute, it is suitable to use as biological weapon and considered as a dangerous biological bioterrorism agent. The aim of this study is to predict an inhibitor of anthrax toxin receptor on human cells by using bioinformatics tools.
Methods: The interaction between anthrax toxin receptor and 57 herbal compounds were studied by using Swissdock webserver. Then the amino acids involved in the strong interactions, were obtained by UCSF Chimera software.
Results: According to the results of this study, among the investigated compounds, 10 compounds include: Asarone, Bisabolol, Chlorogenic acid, Geraniol, Harmine, Harmaline, Sulforaphane, Fluphenazine, L-catechin and D-catechin are capable of inhibiting anthrax toxin receptor. That sulforaphane is probably the most effective inhibitor.
Conclusion: Results derived from processed analyses offer laboratory researches based on these compounds to produce an effective drug against anthrax toxin.