Ribavirin inhibits the replication of infectious bursal disease virus predominantly through depletion of cellular guanosine pool

IntroductionThe antiviral activity of different mutagens against single-stranded RNA viruses is well documented; however, their activity on the replication of double-stranded RNA viruses remains unexplored. This study aims to investigate the effect of different antivirals on the replication of a chicken embryo fibroblast-adapted Infectious Bursal Disease virus, FVSKG2. This study further explores the antiviral mechanism utilized by the most effective anti-IBDV agent.MethodsThe cytotoxicity and anti-FVSKG2 activity of different antiviral agents (ribavirin, 5-fluorouracil, 5-azacytidine, and amiloride) were evaluated. The virus was serially passaged in chicken embryo fibroblasts 11 times at sub-cytotoxic concentrations of ribavirin, 5-fluorouracil or amiloride. Further, the possible mutagenic and non-mutagenic mechanisms utilized by the most effective anti-FVSKG2 agent were explored.Results and DiscussionRibavirin was the least cytotoxic on chicken embryo fibroblasts, followed by 5-fluorouracil, amiloride and 5-azacytidine. Ribavirin inhibited the replication of FVSKG2 in chicken embryo fibroblasts significantly at concentrations as low as 0.05 mM. The extinction of FVSKG2 was achieved during serial passage of the virus in chicken embryo fibroblasts at ≥0.05 mM ribavirin; however, the emergence of a mutagen-resistant virus was not observed until the eleventh passage. Further, no mutation was observed in 1,898 nucleotides of the FVSKG2 following its five passages in chicken embryo fibroblasts in the presence of 0.025 mM ribavirin. Ribavarin inhibited the FVSKG2 replication in chicken embryo fibroblasts primarily through IMPDH-mediated depletion of the Guanosine Triphosphate pool of cells. However, other mechanisms like ribavirin-mediated cytokine induction or possible inhibition of viral RNA-dependent RNA polymerase through its interaction with the enzyme’s active sites enhance the anti-IBDV effect. Ribavirin inhibits ds- RNA viruses, likely through IMPDH inhibition and not mutagenesis. The inhibitory effect may, however, be augmented by other non-mutagenic mechanisms, like induction of antiviral cytokines in chicken embryo fibroblasts or interaction of ribavirin with the active sites of RNA-dependent RNA polymerase of the virus

High resolution inventory and hazard assessment of potentially dangerous glacial lakes in upper Jhelum basin, Kashmir Himalaya, India

In the Himalayan Mountain region, a large number of glacial lakes have developed in the recent past due to glacier recession under the influence of climate change. In this study, we used high resolution satellite data such as Indian Remote Sensing (IRS) LISS-IV (5.8 m) and Google earth images supplemented with field survey to generate an updated glacial lake inventory of Upper Jhelum Basin (UJB) of Kashmir Himalaya. The Sentinel-2A (10 m), Landsat-OLI (30 m) and MSS (60 m), and Cartosat-DEM (30 m) were additional data sources used for glacial lake mapping and change detection analysis. A total of 393 glacial lakes covering an area of 21.55 ± 3.8 km2 were identified, mapped and inventoried. The lake inventory includes 102 proglacial lakes, 13 supraglacial lakes and 278 unconnected glacial lakes. Using the weighted index-based method, 21 glacial lakes were found as Potentially Dangerous Glacial Lakes (PDGLs). Out of these, 7 lakes were classified as High, 9 as Medium and 5 as Low hazard glacial lakes as per the hazard assessment. Change detection analysis of PDGLs from 1980 to 2020 revealed an increase in area from 5.92 km2 to 8.46 km2 thereby, indicating a growth of 2.51 ±0.9 km2(30%) at a rate of 0.063 km2/year. The formation and growth of glacial lakes in this area is attributed to continuous glacier recession under the warming trend of temperature and declining nature of precipitation. In this study, the findings showed that Tavg and Tmin are rising significantly at a rate of 0.004ºC/year and 0.013ºC/year respectively. This study provides an important database for future GLOF studies in the region

Glacial lake changes and the identification of potentially dangerous glacial lakes (PDGLs) under warming climate in the Dibang River Basin, Eastern Himalaya, India

Climate warming has caused accelerated glacier recession in the Eastern Himalayas. This phenomenon has consequently resulted in the development of new glacial lakes and expansion of the existing ones. The outbursts of these lakes has the potential to cause flashfloods with negative impacts for the downstream community. This study used Remote Sensing data products to develop a glacial lake database of Dibang River Basin for the year 2020. The multi-temporal Landsat series data was used to examine the surficial changes in glacial lakes larger than 0.1 km2. The key parameters derived from previous glacial lake studies were used to identify the Potentially Dangerous Glacial Lakes (PDGLs) and conduct their hazard assessment. Finally, the Indian Monsoon Data Assimilation and Analysis (IMDAA) data was used to analyze the Temperature and Precipitation trends from 1980 to 2020 to understand timpact of climate change on lake behaviour. Our findings reveal that the study region has 403 glacial lakes with a total area of 55.73 km2 in 2020. The area of selected glacial lakes has increased from 29.96 km2 in 1985 to 32.56 km2 in 2020 at a rate of 0.07 km2 per year. Twelve (12) lakes were identified as PDGLs in the study region. After applying the weighted index method, 4 lakes among them were categorized as high, 5 as medium and 3 as low hazard glacial lakes. The Mann Kendal test of Tmin, Tmax and Tmean revealed an increasing trend with a Z statics value of >0, whereas mean precipitation on the contrary showed a significant decreasing trend with a Z statics value of <0. The changes in climatic variables (i.e., temperature and precipitation) indicate that the warmer conditions prevail in the region, causing glacier shrinking and retreat, formation of new lakes and expansion of existing ones. Hence, we propose the continuous monitoring and assessment of high hazard glacial lakes for the prevention and mitigation of Glacier Lake Outburst Floods (GLOFs) in the study region

Glacial Lake Outburst Flood Hazard and Risk Assessment of Gangabal Lake in the Upper Jhelum Basin of Kashmir Himalaya Using Geospatial Technology and Hydrodynamic Modeling

Climate warming-induced glacier recession has resulted in the development and rapid expansion of glacial lakes in the Himalayan region. The increased melting has enhanced the susceptibility for Glacial Lake Outburst Floods (GLOFs) in the region. The catastrophic failure of potentially dangerous glacial lakes could be detrimental to human life and infrastructure in the adjacent low-lying areas. This study attempts to assess the GLOF hazard of Gangabal lake, located in the Upper Jhelum basin of Kashmir Himalaya, using the combined approaches of remote sensing, GIS, and dam break modeling. The parameters, such as area change, ice thickness, mass balance, and surface velocity of the Harmukh glacier, which feeds Gangabal lake, were also assessed using multitemporal satellite data, GlabTop-2, and the Cosi–Corr model. In the worst-case scenario, 100% volume (73 × 106 m3) of water was considered to be released from the lake with a breach formation time (bf) of 40 min, breach width (bw) of 60 m, and producing peak discharge of 16,601.03 m3/s. Our results reveal that the lake area has increased from 1.42 km2 in 1972 to 1.46 km2 in 1981, 1.58 km2 in 1992, 1.61 km2 in 2001, 1.64 km2 in 2010, and 1.66 km2 in 2020. The lake area experienced 17 ± 2% growth from 1972 to 2020 at an annual rate of 0.005 km2. The feeding glacier (Harmukh) contrarily indicated a significant area loss of 0.7 ± 0.03 km2 from 1990 (3.36 km2) to 2020 (2.9 km2). The glacier has a maximum, minimum, and average depth of 85, 7.3, and 23.46 m, respectively. In contrast, the average velocity was estimated to be 3.2 m/yr with a maximum of 7 m/yr. The results obtained from DEM differencing show an average ice thickness loss of 11.04 ± 4.8 m for Harmukh glacier at the rate of 0.92 ± 0.40 m/yr between 2000 and 2012. Assessment of GLOF propagation in the worst-case scenario (scenario-1) revealed that the maximum flood depth varies between 3.87 and 68 m, the maximum flow velocity between 4 and 75 m/s, and the maximum water surface elevation varies between 1548 and 3536 m. The resultant flood wave in the worst-case scenario will reach the nearest location (Naranaag temple) within 90 min after breach initiation with a maximum discharge of 12,896.52 m3 s−1 and maximum flood depth and velocity of 10.54 m and 10.05 m/s, respectively. After evaluation of GLOF impacts on surrounding areas, the area under each inundated landuse class was estimated through the LULC map generated for both scenarios 1 and 2. In scenario 1, the total potentially inundated area was estimated as 5.3 km2, which is somewhat larger than 3.46 km2 in scenario 2. We suggest a location-specific comprehensive investigation of Gangbal lake and Harmukh glacier by applying the advanced hazard and risk assessment models/methods for better predicting a probable future GLOF event