Exploring new antiviral targets for influenza and COVID-19: Mapping promising hot spots in viral RNA polymerases

• Autor(a) principal: Figueiredo-Nunes, Inês
• Data de Publicação: 2022
• Outros Autores: Trigueiro-Louro, João, Rebelo-de-Andrade, Helena
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.18/8587
• topic: SARS-CoV-2; COVID-19; Betacoronaviruses; Consensus Druggable Pocket; Conservation Score; Druggability Score; Influenza A Virus; PB1 Protein; Influenza; nsp12 Protein; Infecções Respiratórias; Resistência aos Antimicrobianos

Influenza and COVID-19 are infectious respiratory diseases that represent a major concern to public health with social and economic impact worldwide, for which the available therapeutic options are not satisfactory. The RdRp has a central role in viral replication and thus represents a major target for the development of antiviral approaches. In this study, we focused on Influenza A virus PB1 polymerase protein and the betacoronaviruses nsp12 polymerase protein, considering their functional and structural similarities. We have performed conservation and druggability analysis to map conserved druggable regions, that may have functional or structural importance in these proteins. We disclosed the most promising and new targeting regions for the discovery of new potential polymerase inhibitors. Conserved druggable regions of putative interaction with favipiravir and molnupiravir were also mapped. We have also compared and integrated the current findings with previous research.