Table 2.

In silico studies reported peptide design toward severe acute respiratory syndrome coronavirus 2

Authors/year	Target	Suggested potential therapeutic candidates	Result
Souza PF et al., 2020	S1 and ACE receptor-binding domain	Mo-CBP 3-PepI, Mo-CBP 3-PepII, RcAlb-PepIII, and PepKAA	Mo-CBP3-PepII (85%) and PepKAA (74%) had the highest affinity with it[19]
Chaturvedi et al., 2020	Mutating S protein RBDs	ACE2-peptides (A475V, G476S, S477I, V483A, and V503F)	Starting with appropriate peptide templates based on selected ACE2 segments (natural RBD binder), the templates are gradually changed by random mutations, with the mutations that maximize their RBD-binding free energies being retained[20]
Sasidharan et al., 2020	p18 and p28 against the viral structural S-protein and nonstructural 3CLpro and PLpro proteins	Azurin and its peptides	MD simulations revealed that p28 has a high affinity for S-protein and the ACE2 receptor, implying that p28 could be used as a protein–protein interaction inhibitor[21]
Huang et al., 2020	Blocking the critical spike-RBD and hACE2 interactions	The binding potency of designed peptides to hACE2 was significantly higher than that of the wild-type hACE2 receptor	The top engineered peptide binders had significantly higher binding potency to hACE2 than the wild-type peptide binders (−53.35 vs. −46.46 EvoEF2 energy unit for design and wild type, respectively)[7]
Ling et al., 2020	Heptad repeat 1/2 fusion of spike protein	They ran a simulation of HR1/2 regions and the fusion core on a computer HR1: 919-NQKLIANQFNSAIGKIQDSLS STASALGKLQDVVNQNAQALNTLVKQ-965; HR2:1171-GINASVVNIQKEIDR LNEVAKNLNESLIDL-1200; HR2-anti-P: 1	The binding energy of the HR2-based antiviral peptide to HR1 was 43.0 kcal/mol, which was higher than the natural stage of the fusion core (−33.4 kcal/mol), implying that the expected antiviral peptide would compete with HR1 to prevent the fusion core from forming[22]

RBDs=Receptor-binding domains, ACE=Angiotensin-converting enzyme, hACE2=Human ACE2, HR=Heptad repeat, SARS-CoV-2=Severe acute respiratory syndrome coronavirus 2, Mo-CBP 3-PepI, PepKAA, 3CL, EvoEF2