| Texto completo | |
| Autor(es): |
da Costa, Clauber Henrique Souza
;
de Freitas, Camila Auad Beltrao
;
dos Santos, Alberto Monteiro
;
de Souza, Carlos Gabriel da Silva
;
Silva, Jose Rogerio A.
;
Lameira, Jeronimo
;
Moliner, Vicent
;
Skaf, Munir S.
Número total de Autores: 8
|
| Tipo de documento: | Artigo Científico |
| Fonte: | JOURNAL OF CHEMICAL INFORMATION AND MODELING; v. 65, n. 14, p. 17-pg., 2025-07-11. |
| Resumo | |
The SARS-CoV-2 virus, responsible for the COVID-19 pandemic, has continuously evolved, generating numerous variants with varying degrees of infectivity and transmissibility. The EG.5 subvariant of SARS-CoV-2 emerged globally in mid-2023 as part of the ongoing evolution of the Omicron lineage. Derived from the recombinant XBB.1.9 sublineage, EG.5 has attracted attention due to its enhanced immune escape and sustained transmissibility. As a member of the FLip lineage, EG.5 harbors the convergent F456L mutation in the spike receptor-binding domain (RBD), a key residue for neutralizing antibody recognition. Understanding the molecular mechanisms underlying these variations is crucial for developing effective antiviral strategies. In this study, we employed accelerated molecular dynamics simulations, free-energy calculations, and interaction fingerprint analysis, to investigate the intricate molecular interactions between the spike RBD and the angiotensin-converting enzyme 2 (ACE2) receptor in wild-type SARS-CoV-2 and its variants, specifically Omicron, XBB.1.9.2, and the concerning EG.5 variant. Our findings reveal that electrostatic interactions are the predominant driving force behind the stabilization of the viral spike protein-ACE2 complex. The Omicron, XBB.1.9.2, and EG.5 variants exhibit distinct electrostatic profiles at the spike-ACE2 interface, with mutations at key residues reconfiguring local interactions. These changes enhance ACE2 binding specificity and stabilize the spike-ACE2 complex through intensified electrostatic interactions. The EG.5 variant, with its stronger binding affinity to ACE2, underscores the ongoing threat posed by SARS-CoV-2. The F456L mutation in EG.5 enhances protein stability, further supporting its increased affinity for ACE2. Our research provides valuable insights for designing targeted antiviral therapies, including peptide inhibitors and bioactive compounds. Continuous research is essential to effectively combat COVID-19 and its evolving variants. (AU) | |
| Processo FAPESP: | 22/04695-2 - Mecanismos de reação de enzimas e aprimoramento catalítico com base em estados de transição e algoritmos de aprendizado de máquina |
| Beneficiário: | Alberto Monteiro dos Santos |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 22/04703-5 - Simulações de dinâmica molecular de enzimas de interesse biotecnológico |
| Beneficiário: | Clauber Henrique Souza da Costa |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 23/13707-7 - Estudos Computacionais da Biodegradação Enzimática do Tereftalato de Polietileno (PET): Explorando a Estabilidade e Eficiência das PETases |
| Beneficiário: | Clauber Henrique Souza da Costa |
| Modalidade de apoio: | Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado |
| Processo FAPESP: | 19/17874-0 - EMU concedido no Proc. 2013/08293-7, KAHUNA upgrade - HPE Apollo Gen10 Supercomputer |
| Beneficiário: | Munir Salomao Skaf |
| Modalidade de apoio: | Auxílio à Pesquisa - Programa Equipamentos Multiusuários |
| Processo FAPESP: | 13/08293-7 - CECC - Centro de Engenharia e Ciências Computacionais |
| Beneficiário: | Munir Salomao Skaf |
| Modalidade de apoio: | Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs |