Flaviviruses are small viruses with single-stranded RNA, which include the yellow fever virus, dengue virus, West Nile virus, Japanese encephalitis virus, tick-borne encephalitis virus, and Zika virus; and are causal agents of the most important emerging diseases that have no available treatment to date. In recent years, the strategy has focused on the development of replication inhibitors of these viruses designed to act mainly by affecting the activity of enzyme proteins, such as NS3 and NS5, which perform important functions in the viral replication process. This article describes the importance of flaviviruses and the development of molecules used as inhibitors of viral replication in this genus.
A large number of stool specimens, of healthy newborn infants, collected from various hospitals and clinics in Bangalore City, India, have been examined for the presence of asymptomatic rotaviral excretion. Out of 370 samples analysed during a three year period from 1988 to 1991, 133 specimens (36%) were positive for rotavirus RNA. All these asymptomatic neonatal strains, without exception, showed "long" RNA pattern, but subgroup I specificity. Serotype analysis by ELISA or by hybridization with serotype-specific probes indicated that these strains probably represent a new serotype in newborn children. We find an exclusive association of human rotaviruses having "long" RNA pattern and subgroup I specificity with asymptomatic neonatal infections in contrast to the earlier observations of association of such unusual strains with acute gastroenteritis in young children.
Streptococcus mutans is the main early colonizing cariogenic bacteria because it recognizes salivary pellicle receptors. The Antigen I/II (Ag I/II) of S. mutans is among the most important adhesins in this process, and is involved in the adhesion to the tooth surface and the bacterial co-aggregation in the early stage of biofilm formation. However, this protein has not been used as a target in a virtual strategy search for inhibitors. Based on the predicted binding affinities, drug-like properties and toxicity, molecules were selected and evaluated for their ability to reduce S. mutans adhesion. A virtual screening of 883,551 molecules was conducted; cytotoxicity analysis on fibroblast cells, S. mutans adhesion studies, scanning electron microscopy analysis for bacterial integrity and molecular dynamics simulation were also performed. We found three molecules ZINC19835187 (ZI-187), ZINC19924939 (ZI-939) and ZINC19924906 (ZI-906) without cytotoxic activity, which inhibited about 90% the adhesion of S. mutans to polystyrene microplates. Molecular dynamic simulation by 300 nanoseconds showed stability of the interaction between ZI-187 and Ag I/II (PDB: 3IPK). This work provides new molecules that targets Ag I/II and have the capacity to inhibit in vitro the S. mutans adhesion on polystyrene microplates.
Although acute flaccid paralysis (AFP) surveillance is the “gold standard” for detecting cases of polio, environmental surveillance can provide supplementary information in the absence of paralytic poliomyelitis cases. This study aimed to detect the introduction and/or circulation of wild poliovirus or vaccine-derived polioviruses (VDPV) in wastewater, covering a significant population of Armenia, Colombia, before trivalent oral polio vaccine (OPV) cessation. Between March and September 2015, 24 wastewater samples were collected from eight study sites in eight communes of Armenia, Colombia. Virus detection and characterization were performed using both cell culture (i.e., RD or L20B cells) and RT-PCR. Polioviruses were isolated in 11 (45.8%) of 24 wastewater samples. All isolates were identified as Sabin strains (type 1 = 9, type 3 = 2) by intratypic differentiation. Type 2 poliovirus was not detected in any of the samples. No wild poliovirus or VDPV was detected among the isolates. Non-polio enterovirus was identified in 8.3% (2/24) of the samples. This study revealed the excretion of Sabin poliovirus from OPV-immunized individuals, as well as the absence of VDPV and wild poliovirus in wastewaters of Armenia, Colombia. This confirms that environmental surveillance is an effective method, as an additional support to AFP surveillance, to monitor poliovirus during the OPV-to-IPV (inactivated polio vaccine) transition period.
This study aims to explore a possible silent circulation of wild and vaccine-derived polioviruses in departments of Colombia with polio vaccination coverage of below 80%. The study collected 52 samples of wastewater concentrated as a result of precipitation with polyethylene glycol and sodium chloride. The viral detection was carried out through isolation and the identification through neutralization of the cytopathic effect, as well as through a conventional polymerase chain reaction following reverse transcription. The isolated polioviruses were characterized by the VP1 gene sequence. In two of the 52 samples, there was a presence of the Sabin type 2 poliovirus with more than 99% sequence similarity with the Sabin type 2 strain polio. Circulation of the nonpolio enterovirus was detected in 17.3% of the samples. The serotypes identified corresponded to coxsackievirus B1, echovirus 30, and echovirus 11. No evidence of the spread of either vaccine-derived poliovirus or wild poliovirus was detected in the departments of Colombia with polio coverage lower than 80%.
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