ABSTRACT
The Influenza A virus is a great threat for human health, while various subtypes of the virus made it difficult to develop drugs. With the development of state-of-art computational chemistry, computational molecular docking could serve as a virtual screen of potential leading compound. In this study, we performed molecular docking for influenza A H1N1 (A/PR/8/34) with small molecules such as quercetin and chlorogenic acid, which were derived from traditional Chinese medicine. The results showed that these small molecules have strong binding abilities with neuraminidase from H1N1 (A/PR/8/34). Further details showed that the structural features of the molecules might be helpful for further drug design and development. The experiments in vitro, in vivo have validated the anti-influenza effect of quercetin and chlorogenic acid, which indicating comparable protection effects as zanamivir. Taken together, it was proposed that chlorogenic acid and quercetin could be employed as the effective lead compounds for anti-influenza A H1N1.
Subject(s)
Antiviral Agents/therapeutic use , Chlorogenic Acid/therapeutic use , Drug Evaluation, Preclinical/methods , Influenza, Human/drug therapy , Medicine, Chinese Traditional , Quercetin/therapeutic use , Amino Acid Sequence , Animals , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Chlorogenic Acid/chemistry , Chlorogenic Acid/pharmacology , Cytopathogenic Effect, Viral/drug effects , Female , Humans , Hydrogen Bonding , Influenza A Virus, H1N1 Subtype/drug effects , Influenza, Human/virology , Mice, Inbred BALB C , Molecular Docking Simulation , Molecular Sequence Data , Neuraminidase/antagonists & inhibitors , Neuraminidase/chemistry , Orthomyxoviridae Infections/drug therapy , Orthomyxoviridae Infections/virology , Quercetin/chemistry , Quercetin/pharmacology , Reproducibility of Results , Small Molecule Libraries/pharmacology , ThermodynamicsABSTRACT
AIMS: The relationship between oxidative stress and the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria diagnosed gestational diabetes mellitus GDM isn't well known. Our aim is to evaluate the oxidative stress in women diagnosed by the IADPSG criteria versus the American Diabetes Association (ADA) criteria in China. METHODS: Malondialdehyde (MDA), 8-isoprostane (8IsoP), xanthine oxidize (XO), lipid peroxides (LPO), superoxide dismutase (SOD), glutathione peroxidase (GPX), total antioxidant capacity (TAC), vitamin C (Vc) and vitamins E (Ve) were determined in maternal and cord plasma and placenta of 68 pregnant women. Among these, 28 were diagnosed with GDM while the other 40 were controls. RESULTS: The maternal, cord and placental MDA, XO and 8IsoP levels were significantly higher while SOD and TAC levels were significantly lower in GDM women by either criterion (P < 0.05). XO and 8IsoP levels were higher in ADA group than IADPSG only group while TAC levels significant lower (P < 0.05). Cord MDA, cord and placental XO, and maternal and cord 8IsoP showed significant positive relationship with HbA1c values (P < 0.05). Cord XO levels increased (P < 0.05) while maternal and placental SOD levels decreased (P < 0.05) in women who received cesarean section compared with those delivered normally. Increased XO levels and decreased Ve levels in cord plasma were also found in macrosomia (P < 0.05). CONCLUSIONS: Oxidative stress is present in women diagnosed by IADPSG but to a lesser degree than by ADA. All these women should be monitored and perhaps antioxidant supplemented.