The COVID‐19 (coronavirus disease) global pandemic, caused by the spread of the SARS‐CoV‐2 (severe acute respiratory syndrome coronavirus 2) virus, currently has limited treatment options which include vaccines, anti‐virals, and repurposed therapeutics. With their high specificity, tunability, and biocompatibility, small molecules like peptides are positioned to act as key players in combating SARS‐CoV‐2, and can be readily modified to match viral mutation rate. A recent expansion of the understanding of the viral structure and entry mechanisms has led to the proliferation of therapeutic viral entry inhibitors. In this comprehensive review, inhibitors of SARS and SARS‐CoV‐2 are investigated and discussed based on therapeutic design, inhibitory mechanistic approaches, and common targets. Peptide therapeutics are highlighted, which have demonstrated in vitro or in vivo efficacy, discuss advantages of peptide therapeutics, and common strategies in identifying targets for viral inhibition.
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