scholarly journals Advances in the Development of Antiviral Compounds for Rotavirus Infections

mBio ◽  
2021 ◽  
Vol 12 (3) ◽  
Author(s):  
María Julieta Tohmé ◽  
Laura Ruth Delgui

ABSTRACT Group A rotaviruses (RVAs) are the major cause of severe acute gastroenteritis (AGE) in children under 5 years of age, annually resulting in nearly 130,000 deaths worldwide. Social conditions in developing countries that contribute to decreased oral rehydration and vaccine efficacy and the lack of approved antiviral drugs position RVA as a global health concern. In this minireview, we present an update in the field of antiviral compounds, mainly in relation to the latest findings in RVA virion structure and the viral replication cycle. In turn, we attempt to provide a perspective on the possible treatments for RVA-associated AGE, with special focus on novel approaches, such as those representing broad-spectrum therapeutic options. In this context, the modulation of host factors, lipid droplets, and the viral polymerase, which is highly conserved among AGE-causing viruses, are analyzed as possible drug targets.

2011 ◽  
Vol 140 (2) ◽  
pp. 247-259 ◽  
Author(s):  
O. CASHMAN ◽  
P. J. COLLINS ◽  
G. LENNON ◽  
B. CRYAN ◽  
V. MARTELLA ◽  
...  

SUMMARYCommunity and hospital-acquired cases of human rotavirus are responsible for millions of gastroenteritis cases in children worldwide, chiefly in developing countries, and vaccines are now available. During surveillance activity for human rotavirus infections in Ireland, between 2006 and 2009, a total of 420 rotavirus strains were collected and analysed. Upon either PCR genotyping and sequence analysis, a variety of VP7 (G1–G4 and G9) and VP4 (P[4], P[6], P[8] and P[9]) genotypes were detected. Strains G1P[8] were found to be predominant throughout the period 2006–2008, with slight fluctuations seen in the very limited samples available in 2008–2009. Upon either PCR genotyping and sequence analysis of selected strains, the G1, G3 and G9 viruses were found to contain E1 (Wa-like) NSP4 and I1 VP6 genotypes, while the analysed G2 strains possessed E2 NSP4 and I2 VP6 genotypes, a genetic make-up which is highly conserved in the major human rotavirus genogroups Wa- and Kun-like, respectively. Upon sequence analysis of the most common VP4 genotype, P[8], at least two distinct lineages were identified, both unrelated to P[8] Irish rotaviruses circulating in previous years, and more closely related to recent European humans rotaviruses. Moreover, sequence analysis of the VP7 of G1 rotaviruses revealed the onset of a G1 variant, previously unseen in the Irish population.


2008 ◽  
Vol 51 (2) ◽  
pp. 287-294 ◽  
Author(s):  
Jucélia Stadinicki dos Santos ◽  
Alice Fernandes Alfieri ◽  
José Paulo Gagliardi Leite ◽  
Irene Skraba ◽  
Amauri Alcindo Alfieri

From January/2000 to December/2003, 550 diarrheic fecal samples from the children and adults were collected in several geographical regions of Paraná State, Brazil. The enzyme immunoassay showed 120 (21.8%) samples positive for the group A rotaviruses. One hundred and fourteen samples were genotyped by multiplex-nested-PCR assay. The highest frequency (77.5%) of the positive samples (n=93) was observed in the children under 5 years old. Rotavirus diarrhea was more frequent in the cold and dry seasons of the four evaluated years. The most frequent genotypes were: G1 (50.9%), G4 (9.6%), G9 (7.0%), G2 (1.7%), G3 (0.9%), P[ 8] (71.9%), and P[ 4] (3.5%). The P[ 8] G1 (46.5%) and P[ 8] G4 (9.6%) were the main combinations found to P and G genotypes. The mixed infections, characterized by the rotaviruses with more than one genotype G or P, and nontypeable rotavirus were observed in 8.8, 3.5, and 16.7% of the samples, respectively. The identification of the G9 genotype in the rotavirus strains tested along the four years of studies ratifies the emergency of this genotype also in Paraná State, South region of Brazil, as the worldwide.


Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 959
Author(s):  
Celeste M. Donato ◽  
Julie E. Bines

Group A rotaviruses belong to the Reoviridae virus family and are classified into G and P genotypes based on the outer capsid proteins VP7 and VP4, respectively [...]


1994 ◽  
Vol 6 (2) ◽  
pp. 175-181 ◽  
Author(s):  
A. Lucchelli ◽  
S. Y. Kang ◽  
M. K. Jayasekera ◽  
A. V. Parwani ◽  
D. H. Zeman ◽  
...  

Group A bovine rotaviruses (BRV) have been identified worldwide as a major cause of diarrhea in the young of many species, including humans. Group A rotaviruses are classified into serotypes on the basis of the outer capsid proteins, VP7 (G types) and VP4 (P types). To date, there are 14 G types of group A rotaviruses, with G1, G6, G8, and G10 described for BRV isolates. In this study, G6- and G lo-specific monoclonal antibodies (MAbs) were used in an enzyme-linked immunosorbent assay (ELISA) for the G typing of BRV-positive stool samples from diarrheic beef and dairy calves from South Dakota, Ohio, Michigan, Nebraska, and Washington, USA, and Ontario, Canada. ELISA plates were coated using a broadly reactive VP7 MAb (Common 60) or with G6- or G10-specific MAbs. BRV-positive fecal samples were diluted and added to duplicate wells, followed by the addition of polyclonal guinea pig anti-group A rotavirus serum as the secondary antibody. Several reference G6 and G10 BRV strains as well as other G types previously reported in cattle (G1, G2, G3, G8) and BRV-negative samples were included as G type specificity and negative controls. From a total of 308 field samples analyzed, 79% (244/308) tested positive by the broadly reactive VP7 MAb; of these, 54% (131/244) were G6 positive, 14% (35/244) were G10 positive, 4% (9/244) were both G6 and G10 positive, and 28% (69/244) were G6 and G10 negative. The negative samples may represent additional or undefined serotypes. The 89 samples from South Dakota were further subdivided into samples from beef ( n = 43) or dairy ( n = 46) herds. G6 was more prevalent in beef herd samples (67%) than in dairy herd samples (47.5%). In addition, dairy herds had higher percentages of G10-positive samples (17.5%) G6-G10 double positives (10%), and untypable samples (25%) than did beef herds, in which the prevalence of G10 positive samples was 5.5%, G6-G10 double positives was 5.5%, and untypable samples was 22%. Application of the serotype ELISA for the analysis of additional BRV samples will provide further epidemiologic data on the distribution of BRV serotypes in beef or dairy cattle, an important consideration for the development of improved BRV vaccines.


Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 674
Author(s):  
Anton Yuzhakov ◽  
Ksenia Yuzhakova ◽  
Nadezhda Kulikova ◽  
Lidia Kisteneva ◽  
Stanislav Cherepushkin ◽  
...  

Group A rotavirus (RVA) infection is the leading cause of hospitalization of children under 5 years old, presenting with symptoms of acute gastroenteritis. The aim of our study was to explore the genetic diversity of RVA among patients admitted to Moscow Infectious Disease Clinical Hospital No. 1 with symptoms of acute gastroenteritis. A total of 653 samples were collected from May 2019 through March 2020. Out of them, 135 (20.67%) fecal samples were found to be positive for rotavirus antigen by ELISA. RT-PCR detected rotavirus RNA in 80 samples. Seven G-genotypes (G1, G2, G3, G4, G8, G9, and G12) and three P-genotypes (P[8], P[4], and P[6]) formed 9 different combinations. The most common combination was G9P[8]. However, for the first time in Moscow, the combination G3P[8] took second place. Moreover, all detected viruses of this combination belonged to Equine-like G3P[8] viruses that had never been detected in Russia before. The genotype G8P[8] and G9P[4] rotaviruses were also detected in Moscow for the first time. Among the studied rotaviruses, there were equal proportions of Wa and DS-1-like strains; previous studies showed that Wa-like strains accounted for the largest proportion of rotaviruses in Russia.


ISRN Virology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Christianah Idowu Ayolabi ◽  
David Ajiboye Ojo ◽  
George Enyimah Armah

Approximately over 500,000 children die annually due to severe dehydrating diarrhea caused by rotaviruses. This work investigated rotavirus infection among children less than 5 years with diarrhea in Lagos and determined the circulating electropherotypes and genotypes of the virus isolates. Three hundred and two (n=302) stool samples from children below 60 months were collected from different hospitals and health care centers in Lagos and subjected to enzyme immunoassay (EIA) to determine the presence of Group A rotavirus, RT-PCR to determine the G-types, and polyacrylamide gel electrophoresis (PAGE) to determine the electropherotypes. The results show that 60.3% of the samples showed distinct rotavirus RNA migration pattern, having long electropherotypes (55.3%) of seven variations dominating over the short electropherotypes (44.5%). Six different G-types were detected (G1, G2, G3, G4, G9, and G12). Serotypes G1 and G12 showed long electropherotypic pattern while G2, G3, and G9 exhibited either short or long electropherotype. All G4 detected show short electropherotypic pattern. In conclusion, information on the genomic diversity and RNA electropherotypes of rotaviruses detected in children with diarrhea in Lagos is reported in this study.


2020 ◽  
Vol 2 (3) ◽  
pp. 1-6
Author(s):  
Baratali Rezapour

Preventable factors such as infectious diseases (pneumonia, diarrhea, and malaria), malnutrition and neonatal complications are still the leading cause of child mortality worldwide 1 In 2013, it is estimated that 6.3 million babies born worldwide died before the age of 5, and approximately 9.2% of these deaths were due to diarrheal diseases 2, 3 in simple, accessible ways, and effective treatment can reduce diarrhea-related mortality and make hospital admissions unnecessary, and the role of mothers is the most important 4. Since the presentation of Oral Rehydration Therapy (ORT) in 1979, mortality has reduced. Diarrhea has had a steady downward trend 5. If mothers who have children under 5 years of age, used correctly ORS, they could easily resolve the problem of dehydration in acute diarrhea 6. Mothers didn’t use correctly ORS because of their Low literacy and lack of knowledge and wrong attitude about ORT7. Some health care workers provide mothers’ required equipments, regardless of their educational needs, and mothers may not use ORS. In this study, health workers identified mothers' educational needs and subsequently they trained them about using ORS at home in acute diarrhea in children under 5 years of age


2020 ◽  
Vol 9 (12) ◽  
pp. e1691210755
Author(s):  
Luan Kelves Miranda de Souza ◽  
Kerolayne de Melo Nogueira ◽  
Jand Venes Rolim Medeiros

Diarrhea, which is a gastrointestinal disease, has as its main characteristic the rapid passage of gastric contents through the intestine, which leads to the loss of water and electrolytes and consequent dehydration. The most common fluid replacement is the use of oral rehydration solution (ORS) together with the use of the drug loperamide. However, the use of this medication can cause severe bacteremia followed by sepsis and even death. Currently, there is no effective pharmacological treatment for diarrhea, therefore, it is noted the importance of seeking new therapeutic targets for the treatment of this disease. Thus, the aim of the present study was to conduct a research on the biological activities already described for Diminazene Aceturate with a special focus on antidiarrheal agents. For this, a survey was carried out, through patent filing searches, in the USPTO, EPO, WIPO and INPI databases, using keywords and Boolean operators. Thus, it was found in the international patent databases the number of documents referring to the use of Diminazene Aceturate in several areas, mainly in the pharmaceutical industry, but with a relatively low number of documents regarding the description of possible antidiarrheal action of the compound under study , which reinforces the innovative character of research involving the use of Diminazene Aceturate as an antidiarrheal agent.


1998 ◽  
Vol 36 (1) ◽  
pp. 6-10 ◽  
Author(s):  
Mitsutaka Kuzuya ◽  
Ritsushi Fujii ◽  
Masako Hamano ◽  
Masao Yamada ◽  
Kuniko Shinozaki ◽  
...  

Fecal specimens from patients with acute diarrhea were collected from 10 prefectures in Japan over a 6-month period (November 1992 to April 1993), and the specimens that were negative for human group A rotaviruses were screened for the presence of human group C rotaviruses (CHRVs) by the reverse passive hemagglutination test. Of 784 specimens examined, 53 samples (6.8%) that were collected in 7 of 10 prefectures were positive for CHRV, indicating that CHRVs are widely distributed across Japan. Most of the CHRV isolates were detected in March and April, and CHRVs mainly prevailed in children ages 3 to 8 years. The genome electropherotypes of eight strains isolated in five individual prefectures were surprisingly similar to each other and were different from those of CHRV strains isolated to date. The outer capsid glycoprotein (VP7) gene homologies of the isolates retrieved in 1993 were subsequently analyzed by the dot blot hybridization method. As a result, the VP7 genes of the isolates revealed very high levels of homology not only with each other but also with the VP7 gene of the OK118 strain isolated in 1988. These results suggest that a large-scale outbreak of CHRV occurred during the winter of 1992 and 1993 in Japan.


1969 ◽  
Vol 2 (1) ◽  
pp. 134-137
Author(s):  
Mohammad Hussain ◽  
Manzoor Ali ◽  
S.M.Naeem ◽  
Nisar Ali ◽  
Muhammad Ismail

Introduction: Sacrococcygeal pilonidal disease is a serious health concern because of its associatedcomplications and recurrence. Pilonidal sinus disease is presented with symptoms ranging fromasymptomatic pits to painful draining lesions that are predominantly located in the sacrococcygeal region. Itis characterized by multiple subcutaneous sinuses, containing hairs. The exact etiology of the disease is notknown. Various treatment options are available. The choice of a particular surgical approach depends on thesurgeon's familiarity with the procedure and perceived results. The present study was aimed to compare twotreatment regimens i.e.excision and primary closure verses excision and healing by secondary intention.Patients and methods: The study was conducted in the department of surgery, Saidu Teaching HospitalSaidu Sharif Swat. Forty nine (49) human subjects with informed consent were included in the study.Patients were divided in two groups, depending on their preference and acceptance of the procedure.Patients in group A under went excision of the tract with primary closure of the defect by primary simpleclosure, Rhomboid Limberg flap or by Karydakis procedure. Patients in group B were those in whom sinustracts were excised and wound was left open for healing by secondary intention.Results: Out of the total 49 patients 3 (6.122%) were female. Mean age was 26 years (range 18-40years).Group A comprised of 24 patients in whom wide local excision was performed and wound was closedprimarily while Group B comprised of 25 patients who underwent wide local excision and wound was leftopen for healing by secondary intention. Mean hospital stay of patients in group B was significantly longerthan group A (p=0.002). The mean time for complete healing of the wound after primary closure wasmarkedly shorter.mConclusion: Primary closure of the wound after excision of the sinus tract is preferable over simple excisionand healing by secondary intention.Key words; Pilonidal sinus, primary closure, simple excision.


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