Psoromic acid (PA), a bioactive lichen-derived compound, was investigated for its inhibitory properties against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), along with the inhibitory effect on HSV-1 DNA polymerase, which is a key enzyme that plays an essential role in HSV-1 replication cycle. PA was found to notably inhibit HSV-1 replication (50% inhibitory concentration (IC50): 1.9 μM; selectivity index (SI): 163.2) compared with the standard drug acyclovir (ACV) (IC50: 2.6 μM; SI: 119.2). The combination of PA with ACV has led to potent inhibitory activity against HSV-1 replication (IC50: 1.1 µM; SI: 281.8) compared with that of ACV. Moreover, PA displayed equivalent inhibitory action against HSV-2 replication (50% effective concentration (EC50): 2.7 μM; SI: 114.8) compared with that of ACV (EC50: 2.8 μM; SI: 110.7). The inhibition potency of PA in combination with ACV against HSV-2 replication was also detected (EC50: 1.8 µM; SI: 172.2). Further, PA was observed to effectively inhibit HSV-1 DNA polymerase (as a non-nucleoside inhibitor) with respect to dTTP incorporation in a competitive inhibition mode (half maximal inhibitory concentration (IC50): 0.7 μM; inhibition constant (Ki): 0.3 μM) compared with reference drugs aphidicolin (IC50: 0.8 μM; Ki: 0.4 μM) and ACV triphosphate (ACV-TP) (IC50: 0.9 μM; Ki: 0.5 μM). It is noteworthy that the mechanism by which PA-induced anti-HSV-1 activity was related to its inhibitory action against HSV-1 DNA polymerase. Furthermore, the outcomes of in vitro experiments were authenticated using molecular docking analyses, as the molecular interactions of PA with the active sites of HSV-1 DNA polymerase and HSV-2 protease (an essential enzyme required for HSV-2 replication) were revealed. Since this is a first report on the above-mentioned properties, we can conclude that PA might be a future drug for the treatment of HSV infections as well as a promising lead molecule for further anti-HSV drug design.
- Klíčová slova
- HSV, HSV replication, anti-enzymatic properties, antiherpetic, lichen metabolites, psoromic acid,
- MeSH
- antivirové látky * chemie farmakologie MeSH
- benzoxepiny * chemie farmakologie MeSH
- Cercopithecus aethiops MeSH
- DNA-dependentní DNA-polymerasy * chemie metabolismus MeSH
- inhibitory syntézy nukleových kyselin chemie farmakologie MeSH
- kyseliny karboxylové * chemie farmakologie MeSH
- lidé MeSH
- lidský herpesvirus 1 fyziologie MeSH
- lidský herpesvirus 2 fyziologie MeSH
- lišejníky chemie MeSH
- replikace viru účinky léků MeSH
- simulace molekulového dockingu * MeSH
- Vero buňky MeSH
- virové proteiny * antagonisté a inhibitory chemie metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antivirové látky * MeSH
- benzoxepiny * MeSH
- DNA-dependentní DNA-polymerasy * MeSH
- inhibitory syntézy nukleových kyselin MeSH
- kyseliny karboxylové * MeSH
- psoromic acid MeSH Prohlížeč
- virové proteiny * MeSH
Protected N-branched nucleoside phosphonates containing adenine and thymine bases were prepared as the monomers for the introduction of aza-acyclic nucleotide units into modified oligonucleotides. The phosphotriester and phosphoramidite methods were used for the incorporation of modified and natural units, respectively. The solid phase synthesis of a series of nonamers containing one central modified unit was successfully performed in both 3'→5' and 5'→3' directions. Hybridization properties of the prepared oligoribonucleotides and oligodeoxyribonucleotides were evaluated. The measurement of thermal characteristics of the complexes of modified nonamers with the complementary strand revealed a considerable destabilizing effect of the introduced units. We also examined the substrate/inhibitory properties of aza-acyclic nucleoside phosphono-diphosphate derivatives (analogues of nucleoside triphosphates) but neither inhibition of human and bacterial DNA polymerases nor polymerase-mediated incorporation of these triphosphate analogues into short DNA was observed.
- MeSH
- adenin chemická syntéza chemie MeSH
- DNA-dependentní DNA-polymerasy metabolismus MeSH
- inhibitory syntézy nukleových kyselin chemická syntéza chemie farmakologie MeSH
- lidé MeSH
- nukleosidy chemická syntéza chemie farmakologie MeSH
- oligonukleotidy chemická syntéza chemie farmakologie MeSH
- organofosfonáty chemická syntéza chemie farmakologie MeSH
- sekvence nukleotidů MeSH
- thymin chemická syntéza chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adenin MeSH
- DNA-dependentní DNA-polymerasy MeSH
- inhibitory syntézy nukleových kyselin MeSH
- nukleosidy MeSH
- oligonukleotidy MeSH
- organofosfonáty MeSH
- thymin MeSH
A capillary zone electrophoretic method with indirect UV-detection for determination of rimantadine, an antiviral drug against influenza A, in tablets was validated. Instrumental precision, the method precision, accuracy, calibration curve linearity, selectivity, robustness, and time stability of the sample and the standard were tested. The method was also applied to monitor dissolution tests of the tablets. The possibility of addition of an internal standard for improvement of the method precision was discussed.
- MeSH
- elektroforéza kapilární metody MeSH
- inhibitory syntézy nukleových kyselin analýza chemie MeSH
- rimantadin analýza chemie MeSH
- rozpustnost MeSH
- tablety MeSH
- Publikační typ
- časopisecké články MeSH
- validační studie MeSH
- Názvy látek
- inhibitory syntézy nukleových kyselin MeSH
- rimantadin MeSH
- tablety MeSH
