RESUMO
Viral proteases are highly specific and recognize conserved cleavage site sequences of â¼6-8 amino acids. Short stretches of homologous host-pathogen sequences (SSHHPS) can be found spanning the viral protease cleavage sites. We hypothesized that these sequences corresponded to specific host protein targets since >40 host proteins have been shown to be cleaved by Group IV viral proteases and one Group VI viral protease. Using PHI-BLAST and the viral protease cleavage site sequences, we searched the human proteome for host targets and analyzed the hit results. Although the polyprotein and host proteins related to the suppression of the innate immune responses may be the primary targets of these viral proteases, we identified other cleavable host proteins. These proteins appear to be related to the virus-induced phenotype associated with Group IV viruses, suggesting that information about viral pathogenesis may be extractable directly from the viral genome sequence. Here we identify sequences cleaved by the SARS-CoV-2 papain-like protease (PLpro) in vitro within human MYH7 and MYH6 (two cardiac myosins linked to several cardiomyopathies), FOXP3 (an X-linked Treg cell transcription factor), ErbB4 (HER4), and vitamin-K-dependent plasma protein S (PROS1), an anticoagulation protein that prevents blood clots. Zinc inhibited the cleavage of these host sequences in vitro. Other patterns emerged from multispecies sequence alignments of the cleavage sites, which may have implications for the selection of animal models and zoonosis. SSHHPS/nsP is an example of a sequence-specific post-translational silencing mechanism.
Assuntos
Papaína , Peptídeo Hidrolases , SARS-CoV-2/enzimologia , Proteases Virais/metabolismo , Sequência de Aminoácidos , Miosinas Cardíacas/química , Fatores de Transcrição Forkhead/química , Humanos , Cadeias Pesadas de Miosina/química , Papaína/metabolismo , Peptídeo Hidrolases/metabolismo , Proteína S/química , Receptor ErbB-4/químicaRESUMO
Después del desarrollo y la comercialización en masa de los antibióticos, las bacterias patógenas y ambientales han desarrollado resistencia a los antibióticos desde el siglo pasado, de modo que la infección causada por organismos resistentes a los antibióticos (ORAs) podría ser considerada como una infección emergente. Debido a ello, su control debe ser priorizado ya que constituye una amenaza para todas las naciones, sin reparar en su territorio y situación económica. El incremento de la vigilancia en Estados Unidos de América, Europa y Asia Oriental ha ilustrado lo rápido que pueden diseminarse, trayendo como consecuencia un incremento en la carga de infecciones causadas por los ORAs, sin embargo, la información disponible en los países de continuo desarrollo en América Latina es limitada. Esta revisión describe información reciente de estudios de vigilancia de ORAs en América Latina, así como también fuentes comunes de ORAs y posibles estrategias para su control.
After the development and mass commercialization of antibiotics, pathogenic and environmental bacteria have developed resistance to antibiotics since the last century, so that the infection caused by antibiotic-resistant organisms (AROs) could be considered an emerging infection. As a result, its control should be prioritized as a threat to all nations, regardless of territory and economic situation. Increased surveillance in the United States, Europe and East Asia has illustrated the rapid spread leading to an increasing burden of infections caused by AROs. However, the information available in countries of continued development in Latin America is limited. This review describes recent information on AROs surveillance studies in Latin America as well as common sources of AROs and possible strategies for their control.