Synthesis and structure–activity relationship study of saponin-based membrane fusion inhibitors against SARS-CoV-2

•SAR studies of synthetic saponins regarding their inhibition of SARS-CoV-2′s cell entry.•Development of two minimal synthetic saponins (19 and 20) that are equipotent to platycodin D.•Our newly developed saponin derivatives prevent the fusion between the virus and host cell membranes.•Effectiveness of our newly developed saponin based antiviral agents against all known variants of SARS-CoV-2.