ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global coronavirus disease 2019 (COVID-19) pandemic that has affected the lives of billions of individuals. However, the host-virus interactions still need further investigation to reveal the underling mechanism of SARS-CoV-2 pathogenesis. Here, transcriptomics analysis of SARS-CoV-2 infection highlighted possible correlation between host-associated signaling pathway and virus. In detail, cAMP-protein kinase (PKA) pathway has an essential role in SARS-CoV-2 infection, followed by the interaction between cyclic AMP response element binding protein (CREB) and CREB-binding protein (CBP) could be induced and leading to the enhancement of CREB/CBP transcriptional activity. The replication of Delta and Omicron BA.5 were inhibited by about 49.4% and 44.7% after knockdown of CREB and CBP with small interfering RNAs, respectively. Furthermore, a small organic molecule naphthol AS-E (nAS-E), which targets on the interaction between CREB and CBP, potently inhibited SARS-CoV-2 wild-type (WT) infection with comparable the half-maximal effective concentration (EC50 ) 1.04 µM to Remdesivir 0.57 µM. Compared with WT virus, EC50 in Calu-3 cells against Delta, Omicron BA.2, and Omicron BA.5 were, on average, 1.5-fold, 1.1-fold, and 1.5-fold higher, respectively, nAS-E had a satisfied antiviral effect against Omicron variants. Taken together, our study demonstrated the importance of CREB/CBP induced by cAMP-PKA pathway during SARS-CoV-2 infection, and further provided a novel CREB/CBP interaction therapeutic drug targets for COVID-19.
Subject(s)
COVID-19 , Cyclic AMP Response Element-Binding Protein , Host-Pathogen Interactions , Humans , COVID-19/metabolism , Cyclic AMP/metabolism , Cyclic AMP Response Element-Binding Protein/metabolism , Cyclic AMP-Dependent Protein Kinases/metabolism , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , CREB-Binding Protein/metabolism , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/physiologyABSTRACT
As the most successful therapy for missing teeth, dental implant has become increasingly prevalent around the world. A lot of papers have reported diverse local risk factors affecting the success and survival rate of dental implants, either for a short or a long period. However, there are also many types of systemic disorders or relatively administrated medicine that may jeopardize the security and success of dental implant treatment. Additionally, the coronavirus disease 2019 pandemic also poses a challenge to dental implant clinicians. Some of these risk factors are clinically common but to some extent unfamiliar to dentists, thus optimal measurements are often lacking when they occur in dental clinics. In this review, we analyze potential systemic risk factors that may affect the success rate of dental implants. Some of them may affect bone mineral density or enhance the likelihood of local infection, thus impeding osseointegration. Others may even systemically increase the risk of the surgery and threaten patients' life. In order to help novices receive high-risk patients who need to get dental implant treatment in a more reasonable way, we accordingly review recent research results and clinical experiments to discuss promising precautions, such as stopping drugs that impact bone mineral density or the operation, and addressing any perturbations on vital signs.