In silico evaluation of isatin-based derivatives with RNA-dependent RNA polymerase of the novel coronavirus SARS-CoV-2.

Isatin (1H-indole-2,3-dione)-containing compounds have been shown to possess several remarkable biological activities. We had previously explored a few isatin-based imidazole derivatives for their predicted dual activity against both inflammation and cancer. We explored 47 different isatin-based derivatives (IBDs) for other potential biological activities using in silico tools and found them to possess anti-viral activity. Using AutoDock tools, the binding site, binding energy, inhibitory constant/Ki and receptor-ligand interactions for each of the compounds were analyzed against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). The partition coefficient (logP) values were predicted using MedChem Designer tool. Based on the best Ki, binding energy and the ideal range of logP (between 1.0 and 3.0), 10 out of total 47 compounds were deemed to be prospective RdRp inhibitors. Some of these compounds gave better Ki, binding energy and logP values when compared to standard RdRp inhibitors, such as remdesivir (REM) (Ki = 15.61 µM, logP = 2.2; binding energy = -6.95), a clinically approved RdRp inhibitor and nine other RdRp inhibitors. The results showed that the 10 selected IBDs could be further explored. Molecular dynamics simulations (MDSs) showed that the selected RdRp-IBD complexes were highly stable compared to the native RdRp and RdRp-REM complex during 100 ns time periods. DFT studies were performed for the compounds 16a, 24a, 28a, 38a and 40a, to evaluate the charge transfer mechanism for the interactions between the IBDs and the RdRp residues. Among these, ADME profiling revealed that 28a is a possible lead compound which can be explored further for anti-RdRp activity in vitro. Communicated by Ramaswamy H. Sarma.

Diversity of native larvivorous fish fauna during pre- and post-tsunami in Car Nicobar, Andaman & Nicobar Islands, India.

BACKGROUND & OBJECTIVES: Malaria is a serious public health problem in Car Nicobar Island, Andaman & Nicobar Islands, India. Using larvivorous fishes has proved to be the cheapest method for vector management approach, with long suppression of mosquito population. This study aims to scale-up the diversity of larvivorous fishes and their potential larvivoracity to evolve an appropriate biological intervention strategy against the immature stages of malaria vectors. METHODS: During 2003 (pre-tsunami) and 2014-2016 (post-tsunami), an ecological descriptive survey was carried out in the water bodies around Car Nicobar Island. Fishes were captured using fishing nets and cast nets; and placed in plastic jars and preserved in formalin solution. Fishes were identified and classified according to the available keys. Their abundance and data on the current conservation status was recorded and analyzed. Their potential larvivoracity was graded according to their feeding intensity. RESULTS: Pre-tsunami, a total of 27 larvivorous fish species belonging to 11 orders, 23 families and 23 genera were identified. Order Perciformes and the family Cyprinidae were the most ascendant group constituting 51.9 and 11.1%, respectively. While, 80.8% of species were preferred to inhabit the freshwater region, only 37% of species were surface feeders (SF). According to the conservation, assessment and management plan (CAMP, 1998), 44.4% species were at lower risk least concern (LRlc), while 55.6% species were at least concerned (LC) as per the IUCN, 2017 categorization. However, after the tsunami, 17 fish species had gone extinct and 10 fish species were found to remain alive in the local water bodies. INTERPRETATION & CONCLUSION: Post-tsunami, the larvivoracity analysis indicated that Ophiocara aporos, Ophiocara procephala, Valamugil seheli, Channa punctata, Kuhlia rupestris, Khulia mugil, and Terapon jarbua possess high-level larvivorous potentiality in nature and are recommended for vector control in the study area. These fish species were facing several anthropogenic threats, such as human interference, loss of habitat, trade, overexploitation, and fishing. Therefore, it is important to protect the water bodies from external impact and implement the conservation strategies. Further, periodic fish fauna surveys, identification of breeding sites, scale-up of the larvivorous potentiality at the field level, creating public awareness through health education on establishment of larvivorous fish ponds and planning for mass rearing of the native fish species should be adopted as part of vector management approach in the endemic malarious region of Car Nicobar Island.

Native larvivorous fish diversity as a biological control agent against mosquito larvae in an endemic malarious region of Ranchi district in Jharkhand, India.

BACKGROUND & OBJECTIVES: Mosquitoes are responsible for transmitting several diseases, including malaria, dengue, chikungunya, filariasis, and yellow fever, etc. Release of larvivorous fishes is one of the cheapest method of vector management approach, with long suppression of mosquito population. The present study identifies the native larvivorous fishes and evaluates their potential larvivoracity for biological control of mosquito larvae in an endemic malarious region. METHODS: During the year 2012-13, an ecological descriptive study was carried out in diverse aquatic habitats of fish species found in different areas of Ranchi district, in Jharkhand state of India. Fishes were captured using fishing nets, and identified and classified according to the available keys. Their larvivorous potential was graded according to their feeding potential. Data on current conservation status as well as their abundance were also recorded and analysed. RESULTS: In total, 30 larvivorous fish species belonging to seven orders, 10 families and 21 genera were identified. Order Cypriniformes and the family Cyprinidae were the most ascendant group constituting 66.7 and 60%, respectively. The grading assessment of larvivorous potential for different fish species revealed that, Colisa fasciatus possess maximum larvivoracity (+ + + + +). According to the conservation, assessment and management plan (CAMP, 1998), 60% species were at lower risk near threat (LRnt), while 86.7% species were at least concerned (LC) as per the IUCN, 2017 categorisation. All fish species preferred to inhabit in freshwater. Maximum species occurrence was found in the river (63.3%). Only 30% species were bottom feeders (BF). INTERPRETATION & CONCLUSION: The larvivoracity and habitat distribution analysis indicated that C. fasciatus, Oreochromis mossambica, Esomus danricus, Oryzias melastigma, Puntius sophore, P. ticto, Rasbora daniconius, R. elegans, Aplocheilus panchax, and Danio (B) rerio possess high-level larvivorous potentiality in nature and are recommended for malaria control in the study area. There is an increasing pressure on the fish fauna, of facing several threats, such as fishing, human interference, loss of habitat, overexploitation, pollution, siltation, trade, and diseases. Therefore, periodic survey and monitoring of fish biodiversity, demarcation of breeding sites, field level research study on the efficacy of these fishes, and public awareness on establishment of larvivorous fish ponds should be adopted as a part of the vector management approach in the endemic malarious region of Ranchi district in Jharkhand, India.

Episodes of the epidemiological factors correlated with prevailing viral infections with dengue virus and molecular characterization of serotype-specific dengue virus circulation in eastern India.

BACKGROUND: Dengue is one of the most important and widespread viral infection comprises 4 related serotypes (DEN-1, 2, 3, and 4). Infection with one serotype does not protect against the others, and sequential infections put people at greater risk for dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). This study determines the epidemiology of prevailing viral infections with dengue and molecular characterization of serotype-specific DENV circulation in Odisha of eastern India. METHODS: During the year 2013, 1980 blood samples with suspected dengue cases were obtained between days 1-10 of illness and analyzed by NS1 Ag-RDT, NS1 Ag-ELISA, and RT-PCR. The differential detection of dengue infections and DENV serotyping were carried out by IgM/IgG Ab-ELISA and RT-PCR, respectively. RESULTS: Of the 1980 samples, 733 (37.0%) were positive for dengue RNA by RT-PCR. The confirmed cases of dengue were more in males (73.6%) in comparing to females (26.4%). The age group of 15-44years (527 cases, 71.9%) were more susceptible to dengue infections. 656 (89.5%) cases had infected with monotypic infection by different DENV serotype and 77 (10.5%) cases had multitypic infections by multiple serotypes of DENV. Of the total multitypic infections, there were 74 (10.1%) cases had infected with DENV-2 and DENV-3 serotypes at a time; and only 3 (0.4%) cases had the concurrent infections of all three serotypes that were, DENV-1, DENV-2, and DENV-3. Of the 28 DHF cases, there were 17 (2.3%) cases had infected with multitypic infections and 11 (1.5%) cases had infected with monotypic infection. CONCLUSION: Dengue infections have prevailed from the month of July and grasped it's the peak in September. Rain, temperature and relative humidity have favored the dengue infections. Young adults and males are more susceptible to dengue infections. Serotypes DEN-2 followed by DEN-3 was dominant among the confirmed dengue cases. Co-circulation of multitypic infections with multiple DENV serotypes and the emergence of DHF cases suggested that eastern Indian state Odisha was becoming a hyper-endemic province for dengue; therefore, continuous surveillance is suggested for understanding the epidemiology of the diseases and monitoring the changes in the characteristics of circulating DENV strains.

Prevalence of dengue viral and malaria parasitic co-infections in an epidemic district, Angul of Odisha, India: An eco-epidemiological and cross-sectional study for the prospective aspects of public health.

The co-existence of dengue and malaria infection in an individual and the primary and secondary dengue infection during co-infection were assessed. Over 1 year, 1980 blood samples were collected from suspected cases of dengue fever and analyzed by rapid diagnostic test (RDT), enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) methods to detect dengue infection. RDT and microscopic methods were used to detect malaria. Of the 1980 samples, only 22 (3.0%) cases were identified as dengue-malaria co-infection cases, out of which 13 were male and 9 were female. The highest number of confirmed cases were found during the hot and humid months of September and October (7 cases, 31.8%) and within the over 15 years age group. Of the cases of co-infection, dengue primary infection (21 cases, 95.5%) was significantly more common than dengue secondary infection (1 case, 4.5%) among all of the age groups. There were 12 cases of Plasmodium falciparum and 10 cases of Plasmodium vivax infection among malarial cases. A high prevalence of concurrence of dengue and malaria infection was recorded in this ecosystem. In light of the severity of co-infection and overlapping symptoms, a multidimensional diagnostic approach is suggested.