predictive insights into bioactive compounds from streptomyces as inhibitors of sars-cov-2 mutant strains by receptor binding domain: molecular docking and dynamics simulation approaches

Background: the receptor-binding domain (rbd) of the spike protein of sars-cov-2 interacts with the angiotensinconverting enzyme 2 (ace2) receptor in humans. to date, numerous sars-cov-2 variants, particularly those involving mutations in the rbd, have been identified. these variants exhibit differences in transmission, pathogenicity, diagnostics, and vaccine efficacy. objectives: although therapeutic agents are currently available to inhibit sars-cov-2, most provide supportive and symptomatic relief. moreover, different variants may exhibit resistance to these treatments. this study aimed to identify a potential compound with favorable antiviral effects against sars-cov-2 variants. methods: the study explored drug discovery through structure-based virtual screening of natural products (nps) from the streptomedb database, targeting the ace2-binding pocket of the sars-cov-2 rbd protein. the analysis included the wild-type protein (pdb id: 6vw1) as well as the alpha, beta, delta, lambda, omicron/ba.1, and omicron/ba.2 variants. results: in silico screening identified ‘stambomycin b’ as a potential compound with the highest binding affinity. molecular dynamics simulations of the complexes, conducted over 100 ns, confirmed the prediction that ‘stambomycin b’ could inhibit different sars-cov-2 variants effectively. conclusions: this study concludes that ‘stambomycin b’, a macrolide compound produced by streptomyces ambofaciens, may be a candidate np for effectively combating all mutants that occur in the binding of sars-cov-2 rbd to ace2, even those that may arise in the future.