Large scale peptide screening against main protease of SARS CoV‐2

Abstract

The COVID‐19 pandemic has been a public health emergency, with deadly forms constantly emerging around the world, highlighting the dire need for highly effective antiviral therapeutics. Peptide therapeutics show significant potential for this viral disease due to their efficiency, safety, and specificity. Here, two thousand seven hundred eight antibacterial peptides were screened computationally targeting the Main protease (Mpro) of SARS CoV‐2. Six top‐ranked peptides according to their binding scores, binding pose were investigated by molecular dynamics to explore the interaction and binding behavior of peptide‐Mpro complexes. The structural and energetic characteristics of Mpro‐DRAMP01760 and Mpro‐DRAMP01808 complexes fluctuated less during a 250 ns MD simulation. In addition, three peptides (DRAMP01760, DRAMP01808, and DRAMP01342) bind strongly to Mpro protein, according to the free energy landscape and principal component analysis. Peptide helicity and secondary structure analysis are in agreement with our findings. Interaction analysis of protein‐peptide complexes demonstrated that Mpro's residue CYS145, HIS41, PRO168, GLU166, GLN189, ASN142, MET49, and THR26 play significant contributions in peptide‐protein attachment. Binding free energy analysis (MM‐PBSA) demonstrated the energy profile of interacting residues of Mpro in peptide‐Mpro complexes. To summarize, the peptides DRAMP01808 and DRAMP01760 may be highly Mpro specific, resulting disruption in a viral replication and transcription. The results of this research are expected to assist future research toward the development of antiviral peptide‐based therapeutics for Covid‐19 treatment.

Enzymatic Screening of β-Amyloid Precursor Protein-Based Substrates

“…As Aβs are quite aggregative and cause Alzheimer's-type dementia, BACE1 has been a target enzyme to develop drugs against Alzheimer's disease. Screening a library of substrates to find superior cleavage sequences is quite useful for future drug development [15][16][17]. The digestion of the P 3 library suggested that the Ser(Me) residue is a candidate for future drug design.…”

Isolation, Virtual Screening, and Evaluation of Hazelnut-Derived Immunoactive Peptides for the Inhibition of SARS-CoV-2 Main Protease

“…As a result, peptidyl inhibitors N3 and D-4-77 inhibit M pro , showing half-maximal inhibitory concentrations (IC 50 ) of 125 and 0.95 μM, respectively. Furthermore, bioactive peptides from natural sources that offer efficacy and safety as the potential SARS-CoV-2 M pro have been urgently needed …”

“…Furthermore, bioactive peptides from natural sources that offer efficacy and safety as the potential SARS-CoV-2 M pro have been urgently needed. 29 Bioactive peptides are typically small dietary protein fragments consisting of 2−20 amino acid residues with an average molecular weight of <3 kDa. 30 They are characterized by various physiological activities, such as antioxidative, 31,32 antihypertensive, 33,34 antidiabetic, 35 antimicrobial, 36 and immunomodulatory properties.…”

Antiviral peptides inhibiting the main protease of SARS‐CoV‐2 investigated by computational screening and in vitro protease assay

“…Xia et al designed 229E-HR2P, a peptide for HR1 and HR2 regions of the HCoV-229E that could be utilized as an antiviral drug when accompanied by different antiviral drugs to exert a synergistic effect [30]. From several other studies, it has been demonstrated that several AMPs can also act against a broad range of viruses, referred to as AVPs [31][32][33][34][35][36][37][38]. Several patents of peptides as drug candidates against SARS and MERS are already available, and it is worth noting that peptide inhibitors have the benefits of higher tissue penetration, cost-effectiveness, specificity, and minimal toxicity [39,40].…”

“…The success of this molecule has reinvigorated the investigation for novel protease inhibitors based on peptides and peptidomimetics [47]. Several computational studies also revealed that AVPs may be further developed to inhibit the Mpro of SARS-CoV-2 [37,48]. Virtual screening of a combinatorial peptide library was also conducted against the active sites of Mpro and receptorbinding domain (RBD) [49].…”