Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.2.1.1 (ACS)
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Human adenoviruses (HAdVs) infect respiratory, gastrointestinal, and urinary tracts and give rise to eye infections and epidemic keratoconjunctivitis (EKC). They persist in lymphoid tissue and cause morbidity and mortality in immunocompromised people. Treatments with significant postexposure efficacy are not available. Here, we report that inhibition of the cell cycle-dependent kinase 9 (Cdk9) by RNA interference, or the compound flavopiridol, blocked infections with HAdV-C2/5, EKC-causing HAdV-D8/37, and progeny formation in human corneal epithelial and cancer cells. Flavopiridol abrogated the production of the immediate early viral transactivating protein E1A without affecting nuclear import of viral DNA. In morphometric plaque assays, the compound exhibited antiviral efficacy in both pre- and postexposure regimens with therapeutic indexes exceeding 10. The study identifies Cdk9 as a postexposure drug target against adenovirus infections in vitro and suggests that the clinically tested anticancer drug flavopiridol is a candidate for treating adenoviral EKC or adenovirus emergence upon immune suppression.
ACS Infect Dis 2017 06 09
PMID:Cell Cycle-Dependent Kinase Cdk9 Is a Postexposure Drug Target against Human Adenoviruses. 2843 29

Anthocyanins are bioactive compounds naturally found in a variety of leaves, fruits, and vegetables. Anthocyanin pigments undergo a modification in their chemical structure when exposed to different concentrations of hydrogen ions, and they were extensively studied to be used as active elements in biocompatible pH sensors. The ocular pH is a significant parameter to assess the ocular physiology in cases of postocular surgery, keratoconjunctivitis, and ocular rosacea. Contact lenses have the potential to be used as medical diagnostic devices for in situ continuous monitoring of the ocular physiology. Here, anthocyanin-functionalized contact lenses were developed as wearable sensors to monitor the ocular pH. Anthocyanin pigments were extracted from Brassica oleracea and used to functionalize the polymeric matrices of commercial soft contact lenses by soaking and drop-casting processes. Contact lenses responded to the physiological ocular pH of 6.5, 7.0, and 7.5, exhibiting a systematic color shift from pink (pH 6.5) to purple (pH 7.0) and blue (pH 7.5). The functionalization of contact lens sensors was evaluated as a function of the dye concentration. Quantitative values were obtained by comparing the RGB triplets of the colors obtained with the naturally extracted dye and with delphinidin chloride dye in 0.0 to 1.5 mmol L-1 aqueous solution. The functionalization of contact lenses was studied as a function of the soaking time, resulting in best results when soaking for 24 h. The dye leakage from the contact lenses in deionized water was evaluated, and a negligible leakage after 18 h was observed. Poly-2-hydroxy ethylmethacrylate contact lenses were fabricated and cross-linked with anthocyanin dye, resulting in a slight color shift upon pH changes from 6.5 to 7.4. Contact lens pH sensors may be used to continuously monitor the ocular pH at point-of-care settings.
ACS Omega 2019 Dec 24
PMID:Anthocyanin-Functionalized Contact Lens Sensors for Ocular pH Monitoring. 3189 Oct 56

Coxsackievirus A24 variant (CVA24v) and human adenovirus 37 (HAdV-37) are leading causative agents of the severe and highly contagious ocular infections acute hemorrhagic conjunctivitis and epidemic keratoconjunctivitis, respectively. Currently, neither vaccines nor antiviral agents are available for treating these diseases, which affect millions of individuals worldwide. CVA24v and HAdV-37 utilize sialic acid as attachment receptors facilitating entry into host cells. Previously, we and others have shown that derivatives based on sialic acid are effective in preventing HAdV-37 binding and infection of cells. Here, we designed and synthesized novel pentavalent sialic acid conjugates and studied their inhibitory effect against CVA24v and HAdV-37 binding and infection of human corneal epithelial cells. The pentavalent conjugates are the first reported inhibitors of CVA24v infection and proved efficient in blocking HAdV-37 binding. Taken together, the pentavalent conjugates presented here form a basis for the development of general inhibitors of these highly contagious ocular pathogens.
ACS Chem Biol 2020 10 16
PMID:Pentavalent Sialic Acid Conjugates Block Coxsackievirus A24 Variant and Human Adenovirus Type 37-Viruses That Cause Highly Contagious Eye Infections. 3284 19