The rapid development of the SARS-CoV-2 mediated COVID-19 pandemic has been the cause of significant health concern, highlighting the immediate need for effective antivirals. SARS-CoV-2 is an RNA virus that has an inherently high mutation rate. These mutations drive viral evolution and genome variability, thereby facilitating viruses to have rapid antigenic shifting to evade host immunity and to develop drug resistance. Viral RNA-dependent RNA polymerases (RdRp) perform viral genome duplication and RNA synthesis. Therefore, we compared the available RdRp sequences of SARS-CoV-2 from Indian isolates and the ‘Wuhan wet sea food market virus’ sequence to identify, if any, variation between them. Our data revealed the occurrence of seven mutations in Indian isolates of SARS-CoV-2. The secondary structure prediction analysis of these seven mutations shows that three of them cause alteration in the structure of RdRp. Furthermore, we did protein modelling studies to show that these mutations can potentially alter the stability of the RdRp protein. Therefore, we propose that RdRp mutations in Indian SARS-CoV-2 isolates might have functional consequences that can interfere with RdRp targeting pharmacological agents.
The rapid development of SARS-CoV-2 mediated COVID-19 pandemic has been the cause of significant health concern, highlighting the immediate need for the effective antivirals. SARS-CoV-2 is an RNA virus that has an inherent high mutation rate.These mutations drive viral evolution and genome variability, thereby, facilitating viruses to have rapid antigenic shifting to evade host immunity and to develop drug resistance. Viral RNA-dependent RNA polymerases (RdRp) perform viral genome duplication and RNA synthesis. Therefore, we compared the available RdRp sequences of SARS-CoV-2 from Indian isolates and 'Wuhan wet sea food market virus' sequence to identify, if any, variation between them. We report seven mutations observed in Indian SARS-CoV-2 isolates and three unique mutations that showed changes in the secondary structure of the RdRp protein at region of mutation. We also studied molecular dynamics using normal mode analyses and found that these mutations alter the stability of RdRp protein. Therefore, we propose that RdRp mutations in Indian SARS-CoV-2 isolates might have functional consequences that can interfere with RdRp targeting pharmacological agents.
SARS-CoV-2, the causative agent of the COVID-19 pandemic, is an RNA virus that has inherent high rate of mutation. Due to the mutations, the virus evolves at a rapid pace that helps them to survive better inside the host. One of the hotspots of pharmacological interventions is to inhibit binding of virus with the host cells, which is mediated by Spike glycoprotein of SARS-CoV-2 and ACE2 receptors present on the human cells. This study was conducted with an aim to identify and characterise the mutation (s) present in the Spike glycoprotein of the SARS-CoV-2. Towards this, an
in silico
methodology was used, and the mutations on Spike glycoprotein were identified by comparing the Spike glycoprotein of first reported sequence from Wuhan wet seafood market virus with the available sequences of SARS-CoV-2 from Indian isolates. Our analysis revealed the presence of twenty-five mutations in Spike glycoprotein among Indian SARS-CoV-2 isolates. These mutations spread all over the protein and can be clustered at least into four distinct positions. Further, mutations at eleven positions exhibited alterations in the secondary structure of the polypeptide chain. We also investigated the influence of these mutations on overall protein dynamics and have shown that they affect the dynamic stability of the Spike glycoprotein.
Background: Mercury is the most noxious heavy metal. Because of its environmental persistence and ability to be accumulated in the fatty tissues of aquatic organism, it poses serious threat to the fish community. Methods: In the present study, freshwater air breathing fish Clarias batrachus were exposed separately to different concentrations of Mercury chloride (HgCl2) for 24 hrs, 48 hrs, 72 hrs and 96 hrs. Firstly, median lethal concentration (LC50) of HgCl2 to fish was determined by Probit analysis and was confirmed by pilot test. The behavioral and locomotary changes were monitored.Result: Test group showed random irregular and rapid swimming, restless activity. Along with these activities the test group became hyperactive, started jumping and changing their direction and position in an irregular manner. Some of the noticeable physiological symptoms during the initial stage of toxicity assessment were rapid opercular movement and frequent gulping of air. Both jerky movement and rapid respiratory response were reported to be occasional and slower in the longer duration exposure. Acute toxicity assessment provides first hand information to keep a check on pollution and to observe and track rigours of aquatic ecosystems.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.