Seq12, Seq12m, and Seq13m, peptide analogues of the spike glycoprotein shows antiviral properties against SARS-CoV-2: An in silico study through molecular docking, molecular dynamics simulation, and MM-PB/GBSA calculations

Abstract

At the very beginning of the new decade, the COVID-19 pandemic has badly hit modern human societies. SARS-CoV-2, the causative agent of COVID-19 acquiring mutations and circulating as new variants. Herein, we have found three new antiviral peptides (AVPs) against the SARS-CoV-2. These AVPs are analogous to the spike glycoprotein of the SARS-CoV-2. Antiviral peptides, i.e. , Seq12, Seq12m, and Seq13m, can block the receptor-binding domain (RBD) of the SARS-CoV-2, which is necessary for communicating with the angiotensin-converting enzyme 2 (ACE2). Also, these AVPs sustain their antiviral properties, even after the insertion of 25 mutations in the RBD (Rosetta and FoldX based). Further, Seq12 and Seq12m showed negligible cytotoxicity. Besides, the binding free energies calculated using MM-PB/GBSA method are also in agreement with the molecular docking studies. The molecular interactions between AVPs and the viral membrane protein (M) also showed a favorable interaction suggesting it could inhibit the viral re-packaging process. In conclusion, this study suggests Seq12, Seq12m, and Seq13m could be helpful to fight against SARS-CoV-2. These AVPs could also aid virus diagnostic tools and nasal spray against SARS-CoV-2 in the future.

Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2

“…A collection of 100,000 FDA-registered chemicals and approved drugs, as well as about 14 million other purchasable chemicals against multiple SARS-CoV-2 targets, was screened for drug repurposing, 744 where SVM was applied for identifying the top features. Additionally, Dutta et al 745 predicted a novel peptide analog of the S protein using SVM models implemented by the AVPred antiviral peptide prediction server.…”

“…One study predicted the affinities of the peptide analogues Seq12, Seq12m, and Seq13m to S protein through molecular docking, MD simulation, and MM-PB/GBSA calculations. 745 Other docking and MD studies of peptides to S protein include refs ( 876 and 972 − 981 ). In addition, potency of peptides to other targets was also anticipated.…”

Allosteric Site of ACE-2 as a Drug Target for COVID-19

“… 3 At present, most targets against SARS-CoV-2 are focused on the viral RNA-dependent RNA polymerase (RdRp), the main viral protease (M pro ), the spike protein, and the receptor-binding domain (RBD, e.g., fusion inhibitors, ACE-2 contact inhibitors). 4 Vaccines designed using the spike protein of SARS-CoV-2 offer a proactive immune option that produces monoclonal antibodies against the spike protein of SARS-CoV-2. However, mutations are present in the spike protein, for instance, in the delta and omicron variants of SARS-CoV-2.…”

“…The biophysical properties of ACE-2 play an important role because they are essential for interactions between ACE-2 and the viral RBD. 4 Altering the biophysical properties of ACE-2 has a strong effect on the biophysical interactions between ACE-2 and the viral RBD. In other words, due to altered biophysical properties of the ACE-2 receptor, the viral RBD may lose or improve the degree of affinity toward the ACE-2 receptor.…”

“…SARS-CoV-2 that caused COVID-19 uses membrane-bound angiotensin-converting enzyme-2 (ACE-2) together with an auxiliary receptor, transmembrane protease serine 2 (TMPRSS2), to enter into the host cells . At present, most targets against SARS-CoV-2 are focused on the viral RNA-dependent RNA polymerase (RdRp), the main viral protease (M pro ), the spike protein, and the receptor-binding domain (RBD, e.g., fusion inhibitors, ACE-2 contact inhibitors) . Vaccines designed using the spike protein of SARS-CoV-2 offer a proactive immune option that produces monoclonal antibodies against the spike protein of SARS-CoV-2.…”