Design and selection of peptides to block the SARS-CoV-2 receptor binding domain by molecular docking

Abstract

The novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is currently one of the most contagious viruses in existence and the cause of the worst pandemic in this century, COVID-19. SARS-CoV-2 infection begins with the recognition of the cellular receptor angiotensin converting enzyme-2 by its spike glycoprotein receptor-binding domain (RBD). Thus, the use of small peptides to neutralize the infective mechanism of SARS-CoV-2 through the RBD is an interesting strategy. The binding ability of 104 peptides (University of Nebraska Medical Center’s Antimicrobial Peptide Database) to the RBD was assessed using molecular docking. Based on the molecular docking results, peptides with great affinity to the RBD were selected. The most common amino acids involved in the recognition of the RBD were identified to design novel peptides based on the number of hydrogen bonds that were formed. At physiological pH, these peptides are almost neutral and soluble in aqueous media. Interestingly, several peptides showed the capability to bind to the active surface area of the RBD of the Wuhan strain, as well as to the RBD of the Delta variant and other SARS-Cov-2 variants. Therefore, these peptides have promising potential in the treatment of the COVID-19 disease caused by different variants of SARS-CoV-2. This research work will be focused on the molecular docking of peptides by molecular dynamics, in addition to an analysis of the possible interaction of these peptides with physiological proteins. This methodology could be extended to design peptides that are active against other viruses.

Virtual Screening of Peptide Libraries: The Search for Peptide-Based Therapeutics Using Computational Tools

“…Briefly, SARS-CoV-2 belongs to the enveloped viruses, including a positive-sense single-stranded RNA, and its genome encodes different viral proteins supporting its infective action [176]. For instance, the SARS-CoV-2 spike protein binds to the human receptor angiotensin-converting enzyme 2 (ACE2) through a receptor-binding domain (RBD), thus allowing viral entry into host cells [176,[183][184][185][186][187][188][189][190]. In addition, the 3C-like protease (3CLpro), also known as main protease (Mpro), is a viral protein with a key role in the processing of the polyprotein precursors pp1a and pp1b into the functional proteins necessary for viral propagation [176,[191][192][193][194].…”

“…To discover peptide ligands of the spike RBD that could reduce SARS-CoV-2 infectivity by blocking viral entry, a work by Ramirez-Acosta and collaborators reported on a virtual screening strategy employing antimicrobial peptides [190]. A library of 104 peptides was assembled starting from the Antimicrobial Peptide Database (APD) of the University of Nebraska Medical Center [170,206] by focusing on those peptides with known antiviral activities [190]. Since lysozyme is an innate immune system component with antimicrobial activity, three lysozyme fragments were inserted into the library [190].…”

Synergistic peptide combinations designed to suppress SARS-CoV-2

“…Recently, Surfactin-like lipopeptides from Bacillus clausii demonstrated efficient binding of S1 and inhibition of virus entry, presenting a potential alternative for treating SARS-CoV-2 infection [ 16 ]. Studies have indicated that a peptide cocktail derived from SARS-CoV-2 can provide strong protection against viral infection [ 17 , 18 ]. We hypothesize that combinations of peptides targeting various stages of viral invasion (such as ACE2 and S protein binding and membrane fusion) may effectively and comprehensively prevent the spread of SARS-CoV-2 and its variants.…”

Prospecting native and analogous peptides with anti-SARS-CoV-2 potential derived from the trypsin inhibitor purified from tamarind seeds

“…Briefly, TMPRSS2-mediated protein S cleavage may trigger membrane fusion to release the viral genome into the cytoplasm ( Belouzard et al, 2012 ). The SARS-CoV-2 infects cells via a critical protein-protein interaction (PPI) between the SARS-CoV S-protein receptor binding domain (RBD) with the protease domain (PD) of the human cell surface receptor angiotensin-converting enzyme 2 (ACE-2) ( Morgan et al, 2021 , Ramirez-Acosta et al, 2022 ).…”