Viveca Giongo

Caulerpin as a potential antiviral drug against herpes simplex virus type 1

About 80% of the human adult population is infected with HSV-1. Although there are many anti-HSV-1 drugs available (acyclovir, ganciclovir, valaciclovir, foscarnet), their continuous use promotes the selection of resistant strains, mainly in ACV patients. In addition to resistance, the drugs also have toxicity, particularly when administration is prolonged. The study of new molecules isolated from green algae with potential antiviral activity represents a good opportunity for the development of antiviral drugs. Caulerpin, the major product from the marine algae Caulerpa Lamouroux (Caulerpales), is known for its biological activities such as antioxidant, antifungal, acetylcholinesterase inhibitor (AChE) and antibacterial activity. In this work, we show that caulerpin could be an alternative to acyclovir as an anti-HSV-1 drug that inhibits the alpha and beta phases of the replication cycle.

Marine natural seaweed products as potential antiviral drugs against Bovine viral diarrhea virus

Bovine viral diarrhea virus (BVDV) is an etiologic agent that causes important economic losses in the world. It is endemic in cattle herds in most parts of the world. The purpose of this study was to evaluate the in vitro cytotoxic effect and antiviral properties of several marine natural products obtained from seaweeds: the indole alkaloid caulerpin (CAV, 1) and three diterpenes: 6-hydroxydichotoma-3,14-diene-1,17-dial (DA, 2), 10,18-diacetoxy-8-hydroxy-2,6-dolabelladiene (DB1, 3) and 8,10,18-trihydroxy-2,6-dolabelladiene (DB3, 4). The screening to evaluate the cytotoxicity of compounds did not show toxic effects to MDBK cells. The antiviral activity of the compounds was measured by the inhibition of the cytopathic effect on infected cells by plaque assay (PA) and EC50 values were calculated for CAV (EC=2,0± 5.8), DA (EC 2,8± 7.7), DB1 (EC 2,0±9.7), and DB3 (EC 2,3±7.4). Acyclovir (EC50 322± 5.9) was used in all experiments as the control standard. Although the results of the antiviral activity suggest that all compounds are promising as antiviral agents against BVDV, the Selectivity Index suggests that DB1 is the safest of the compounds tested.

Evaluation of the acute toxicity of dolabelladienotriol, a potential antiviral from the brown alga Dictyota pfaffii, in BALB/c mice

Dolabelladienotriol is a product extracted from the brown marine alga Dictyota pfaffii from Brazil that has been shown to have antiviral activity and low cytotoxicity. Our studies have evaluated the acute toxicity of dolabelladienotriol in BALB/c mice for ten days after administration of a single dose. Among the parameters considered were behavior, weight, biochemical and histological analyses of blood samples taken at three different times (Bs.0, Bs.1 and Bs.2) and optical microscopic examination of organs like liver, kidney, stomach and small intestine. Mice deaths were not observed at any dose during the ten day period. There were some changes in the biochemical analysis results for urea nitrogen (BUN) and alanine aminotransferase (ALT), but the changes were not significantly different from the reference levels of the animals before administration of the substance. Histological analyses of tissues were very similar for all animals. The alterations in liver and kidney tissues did not affect the animals´ behavior at any concentration, not even at 50 mg/kg, where the most significant changes in tissues were seen. This study indicates that dolabelladienotriol has low toxicity in administered dose range.

Molecular modeling of a phenyl-amidine class of NMDA receptor antagonists and the rational design of new triazolyl-amidine derivatives.

Recently, many efforts have been made to develop N‐methyl‐d‐aspartic acid receptor antagonists for treating different pathological conditions such as thrombo‐embolic stroke, traumatic head injury, Huntington’s, Parkinson’s, and Alzheimer’s diseases). However, as side‐effects limit the use of most antagonists, new drugs are still required. In this work, we performed a (quantitative) structure‐activity relationship analysis of 17 phenyl‐amidine derivatives (1a–1q), reported as N‐methyl‐d‐aspartic acid receptor antagonists, and used this data to rationally design the triazolyl‐amidines. The best (quantitative) structure‐activity relationship model constructed by multiple linear regression analysis presented high data fitting (R = 0.914) was able to explain 83.6% of the biological data variance (R2 = 0.836), presented a satisfactory internal predictive ability (Q2 = 0.609) and contained the descriptors (EHOMO, Ovality and cLogP). Our assays confirmed that glutamate promotes an extensive cell death in avian neurons (77%) and 2a and 2b protected the neurons from the glutamate effect (from 77% to 27% and 45%, respectively). The results of neurotoxicity and cytotoxicity on Vero cells suggested the favorable profile of 2a and 2b. Also, the molecular modeling used to predict the activity, the interaction with the receptor and the pharmacokinetic and toxicity of the triazolyl‐amidines pointed them as a promising class for further exploration as N‐methyl‐d‐aspartic acid receptor antagonists.

Subchronic toxicity and anti-HSV-1 activity in experimental animal of dolabelladienetriol from the seaweed, Dictyota pfaffii

&NA; This study examined in rats the subchronic toxicity and anti‐ HSV‐1activity after oral administration of dolabelladienetriol (D1), a diterpene isolated from the seaweed Dictyota pfaffii. In subchronic toxicity (SCT) tests, female rats received D1 by gavage 15 mg/kg/day (n = 5) for 50 days, and general behavior, death, hematological, biochemical and histological changes in the liver, kidney, stomach, and duodenum were determined. For the anti‐HSV‐1 activity, female mice were infected and treated orally with a dose of 20 mg/kg (n = 5) twice a day with D1 and any lesions in the skin were then recorded for 18 days. Dolabelladienetriol in SCT did not significantly change behavior, body weight, hematological or biochemical profiles. The liver and kidneys, however, showed some alterations in rats treated with D1, similar to those in rats treated with ACV, while the other tissues had no significant changes. The anti‐HSV‐1 activity of D1 had a similar efficacy to the ACV drug control in mice. Our results showed that D1 has potential commercial development as a new HSV‐1drug. HighlightsSubchronic oral toxicity of dolabelladienetriol tested in Wistar rats.Low toxicity of dolabelladienetriol in 15 mg/kg concentration for 50 days.Therapeutic effective of dolabelladienetriol (20/mg/day) against HSV‐1 in BALB/c.

Study of Virioplankton Abundance and Morphological Diversity in a Brazilian Coastal Region Influenced by Upwelling System

Marine viruses are among the most common, abundant and diverse biological entities in seawater columns. Despite this, little is yet know about virus abundance and distribution in tropical aquatic ecosystems. Here, we evaluated virus abundance and their relationship to host and environment variables within Arraial do Cabo upwelling system, Rio de Janeiro State, Southeast of Brazil. Seawater samples were collected in four seasonal campaigns from five sampling sites including different ar eas of human settlement characterized by anthropogenic activity (sewage disposal/ port activity) and upwelling phenomena. Virioplankton abundance ranged from 0.79 to 7.95 x10 8 .part.mL -1 , whereas bacterioplankton abundance ranged from 2.6 to 13.4 x107.cell.mL-1. Viruses distribution was evaluated in relation to their possible hosts, and viral abundance positively correlated with both bacteria (r = 0.65; p < 0.01) and chlorophyll-a (r = 0.61; p < 0.01). Additionally, a method of concentration using adsorption/elution into electronegative membrane combined to electron microscopy, revealed the presence of bacteriophages, belonging to Myoviridae and Podoviridae families. Principal component analysis showed clear evidence that there is a seasonal influence between Arraial do Cabo biotic and abiotic variables, and that the high abundance of viruses was correlated mainly with nitrogen inorganic forms (NO 2 - and NO 3 -), PO 4 3- , chlorophyll-a and bacteria. Thus, our study indicated that viral abundance in Arraial do Cabo coastal region depends on host cell abundance, which appears to be controlled mainly by nutrient availability.