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Clinically validated examples of in silico and structure-based approaches contributing directly to approved therapeutics include the development of HIV protease inhibitors in the 1990sthe first drugs designed using computational structureactivity relationshipsand the more recent application of GPCR crystal structures to guide ligand optimization for receptors, including the 2-adrenoceptor and GLP-1 receptor (Zhao et al., 2020)

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