RESUMO
A serious pandemic has been caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The interaction between spike surface viral protein (Sgp) and the angiotensin-converting enzyme 2 (ACE2) cellular receptor is essential to understand the SARS-CoV-2 infectivity and pathogenicity. Currently, no drugs are available to treat the infection caused by this coronavirus and the use of antimicrobial peptides (AMPs) may be a promising alternative therapeutic strategy to control SARS-CoV-2. In this study, we investigated the in silico interaction of AMPs with viral structural proteins and host cell receptors. We screened the antimicrobial peptide database (APD3) and selected 15 peptides based on their physicochemical and antiviral properties. The interactions of AMPs with Sgp and ACE2 were performed by docking analysis. The results revealed that two amphibian AMPs, caerin 1.6 and caerin 1.10, had the highest affinity for Sgp proteins while interaction with the ACE2 receptor was reduced. The effective AMPs interacted particularly with Arg995 located in the S2 subunits of Sgp, which is key subunit that plays an essential role in viral fusion and entry into the host cell through ACE2. Given these computational findings, new potentially effective AMPs with antiviral properties for SARS-CoV-2 were identified, but they need experimental validation for their therapeutic effectiveness.
Assuntos
Enzima de Conversão de Angiotensina 2/química , Tratamento Farmacológico da COVID-19 , SARS-CoV-2/química , Glicoproteína da Espícula de Coronavírus/química , Proteínas de Anfíbios/química , Proteínas de Anfíbios/uso terapêutico , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Antivirais/química , Antivirais/uso terapêutico , Sítios de Ligação/genética , COVID-19/genética , COVID-19/virologia , Simulação por Computador , Humanos , Pandemias , Proteínas Citotóxicas Formadoras de Poros/química , Proteínas Citotóxicas Formadoras de Poros/uso terapêutico , Ligação Proteica/genética , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/uso terapêutico , Proteínas Estruturais Virais/química , Proteínas Estruturais Virais/genética , Proteínas Estruturais Virais/uso terapêuticoRESUMO
Anionic antimicrobial peptides (AAMPs) with net charges ranging from -1 to -8 have been identified in frogs, toads, newts and salamanders across Africa, South America and China. Most of these peptides show antibacterial activity and a number of them are multifunctional, variously showing antifungal activity, anticancer action, neuropeptide function and the ability to potentiate conventional antibiotics. Antimicrobial mechanisms proposed for these AAMPs, include toroidal pore formation and the Shai-Huang-Matsazuki model of membrane interaction along with pH dependent amyloidogenesis and membranolysis via tilted peptide formation. The potential for therapeutic and biotechnical application of these AAMPs has been demonstrated, including the development of amyloid-based nanomaterials and antiviral agents. It is concluded that amphibian AAMPs represent an untapped potential source of biologically active agents and merit far greater research interest.