Table 1.

Summary of the different potential therapies targeting SARS-CoV-2 S protein

Treatment	Source	Mechanism of action	Clinical phases (87)
Natural/ Repurposed products
Linoleic acid	N-6 polyunsaturated fatty acid (PUFA) obtained from vegetable oil	It binds to LA-binding pocket in RBDs of S Protein	NA, Potential drug
Emodin	Natural anthraquinon	Potentially inhibits the S protein and ACE-2 receptor interaction, suppresses the inflammation associated with COVID-19	NA, Potential drug
Bisoxatin	Synthetic drug	Significantly binds to RBD of S protein	NA, computational studies, potential lead compound
Natural lectins
GRFT (Griffithsin)	Algae-derived lectin isolated from the red alga Griffithsia sp.	Binds to the glycosylation sites of S1 subunit, preventing the subsequent steps essential for viral entry	In vitro studies, Phase: NA
FRIL	Glucose/ mannose lectin isolated from Lablab purpureus plant	Binds to the high-mannose glycans and complex-type N-glycans	In vitro studies
Antiviral peptides
EK1C4	Synthetic lipopeptide	Targets the HR1 domains of S protein; thus, forming a 6-HB structure similar to the native one, results in inhibiting the viral fusion	Preclinical (In vivo studies)
SBP1	Synthetic peptide	Mimics the residues 21–43 of ACE-2 PD α1 helix sequence, and binds to the RBD, disrupting the ACE-2 and S protein interaction	Potential inhibitors require further testing in animal and human cells
Recombinant-based therapy
Recombinant Soluble ACE-2	Human recombinant	Competitively binds to S protein and distracts the virus from the membrane-bound ACE-2 receptors	Randomized Interventional (Clinical Trial), Phase: NA
Casirivimab, Imdevimab, Bamlanivimab and Etesevimab	Neutralizing monoclonal antibodies (mAbs)	Bind to the SARS-CoV-2 S protein RBD and inhibits its attachment to ACE2	FDA authorized for emergency emergency use (phase II–III clinical trials)