In-silico ADMET and molecular docking evaluation of an active cyclopeptide from a Saharan Streptomyces strain with anticancer, anti-HIV, and anti- SARS-CoV-2 activities

The emergence of new SARS-CoV-2 variants, HIV drug resistance, and the persistent burden of breast cancer have created an urgent need to identify new antiviral and anticancer drug candidates. In this investigation, we employed in-silico methods to evaluate the pharmacokinetic proprieties and toxicity, and the inhibitory potential of a cyclic peptide compound produced by a novel Streptomyces strain using target enzymes. In silico analysis of the ADMET profile indicates that the cyclic peptide cyclo(L-pro-L-tyr) has favorable physicochemical properties, good lipophilicity and water solubility, generally favorable pharmacokinetic characteristics, and low toxicity for the cyclic peptide. In addition, the docking studies of the compound showed strong binding affinities with HIV-1 integrase at -7.4 kcal/mol, HIV-1 reverse transcriptase at -8.1 kcal/mol, COVID-19 main protease at -8.5 kcal/mol, and SARS-CoV-2 spike glycoprotein at -7.7 kcal/mol compared to references inhibitors. Furthermore, it has a good binding affinity with estrogen receptor alpha associated with breast cancer at -6.8 kcal/mol compared to reference inhibitors. Therefore, the findings demonstrate the potential of cyclo(L-pro-L-tyr) as a novel bioactive compound with antiviral and anticancer properties. This means that it needs to be tested in more experiments and further developed as a lead compound for treating SARS-CoV-2 infections, HIV/AIDS, and breast cancer.