In silico and structure-based evaluation of deleterious mutations identified in human Chk1, Chk2, and Wee1 protein kinase.

Checkpoint kinases Chk1, Chk2, Wee1 are playing a key role in DNA damage response and genomic integrity. Cancer-associated mutations identified in human Chk1, Chk2, and Wee1 were retrieved to understand the function associated with the mutation and also alterations in the folding pattern. Therefore, an attempt has been made to identify deleterious effect of variants using in silico and structure-based approach. Variants of uncertain significance for Chk1, Chk2, and Wee1 were retrieved from different databases and four prediction servers were employed to predict pathogenicity of mutations. Further, Interpro, I-Mutant 3.0, Consurf, TM-align, and have (y)our protein explained were used for comprehensive study of the deleterious effects of variants. The sequences of Chk1, Chk2, and Wee1 were analyzed using Clustal Omega, and the three-dimensional structures of the proteins were aligned using TM-align. The molecular dynamics simulations were performed to explore the differences in folding pattern between Chk1, Chk2, Wee1 wild-type, and mutant protein and also to evaluate the structural integrity. Thirty-six variants in Chk1, 250 Variants in Chk2, and 29 in Wee1 were categorized as pathogenic using in silico prediction tools. Furthermore, 25 mutations in Chk1, 189 in Chk2, and 14 in Wee1 were highly conserved, possessing deleterious effect and also influencing the protein structure and function. These identified mutations may provide underlying genetic intricacies to serve as potential targets for therapeutic inventions and clinical management.

Comprehensive Analysis of Antioxidant Properties, GC-MS, and FTIR profiles of Myrica esculenta Fruit Extracts from Western East Khasi Hills of Meghalaya.

This study investigates the phytoconstituents of Myrica esculenta fruit extracts using various solvents, including n-hexane, dichloromethane, ethyl acetate, methanol, and water. Qualitative phytochemical analysis revealed the presence of several phytochemicals, with the highest concentration found in the methanol extract. The total phenolic (94.5 ± 0.96 mg gallic acid equivalent (GAE)/g) and flavonoid (74.27 ± 0.29 mg quercetin equivalent (QE)/g) contents were also highest in the methanol extract. Antioxidant activity was measured using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic) acid (ABTS), and Ferric Reducing Antioxidant Power (FRAP) assays. The methanol extract exhibited superior antioxidant activity with DPPH and ABTS IC50 values of 22.27 ± 0.98 µg/ml and 19.69 ± 0.36 µg/ml, respectively, compared to ascorbic acid. FRAP activity was also highest in the methanol extract (87.125 ± 0.33 mg Trolox equivalents (TE)/g). Gas Chromatography-Mass Spectrometry (GC-MS) analysis identified antioxidant compounds hexanedioic acid, bis(2-ethylhexyl) ester, methyl 11,12-octadecadienoate, and pentadecanoic acid. while Fourier Transform Infrared Spectroscopy (FTIR) analysis detected functional groups such as alkenes, ketones, esters, alcohols and carboxylic acids. These findings suggest that the methanolic extract of M. esculenta fruits is a rich source of natural antioxidants, making it suitable for pharmaceutical, health, and nutritional supplements aimed at enhancing overall health.

Does social media provide adequate health education for prevention of COVID-19? A case study of YouTube videos on social distancing and hand-washing.

Social media offers an opportune platform for educating the public about the recommended interventions during global health emergencies. This case study evaluated information in the popular social media platform YouTube about two key interventions (namely, 'social distancing' and 'hand washing') recommended during coronavirus disease-2019. Using the keywords 'social distancing' and 'hand washing', 77 and 78 videos, respectively, were selected from YouTube through pre-defined criteria. The understandability, actionability and quality of information in these videos were assessed. Cumulatively, the social distancing videos received >9 million views and the hand-washing videos received >37 million views. Thirteen social distancing videos (16.9%) and 46 hand-washing videos (58.9%) provided understandable, actionable and good-quality information. The non-understandable, non-actionable or poor-quality videos had paradoxically more viewer engagements than the understandable, actionable or good-quality videos, respectively. Most social distancing videos came from news agencies (68.8%). Hand-washing videos were mostly uploaded by health agencies or academic institutes (52.6%). The videos were less likely to be understandable and actionable and to be of good quality when uploaded by sources other than health agencies or academic institutes. The paucity of adequate information and the limited representation of 'authoritative' sources were concerning. Strategies for harnessing social media as an effective medium for public health education are necessary during pandemics.

Identification of potential plant-based inhibitor against viral proteases of SARS-CoV-2 through molecular docking, MM-PBSA binding energy calculations and molecular dynamics simulation.

The Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus, SARS-CoV-2, has recently emerged as a pandemic. Here, an attempt has been made through in-silico high throughput screening to explore the antiviral compounds from traditionally used plants for antiviral treatments in India namely, Tea, Neem and Turmeric, as potential inhibitors of two widely studied viral proteases, main protease (Mpro) and papain-like protease (PLpro) of the SARS-CoV-2. Molecular docking study using BIOVIA Discovery Studio 2018 revealed, (-)-epicatechin-3-O-gallate (ECG), a tea polyphenol has a binding affinity toward both the selected receptors, with the lowest CDocker energy - 46.22 kcal mol-1 for SARS-CoV-2 Mpro and CDocker energy - 44.72 kcal mol-1 for SARS-CoV-2 PLpro, respectively. The SARS-CoV-2 Mpro complexed with (-)-epicatechin-3-O-gallate, which had shown the best binding affinity was subjected to molecular dynamics simulations to validate its binding affinity, during which, the root-mean-square-deviation values of SARS-CoV-2 Mpro-Co-crystal ligand (N3) and SARS-CoV-2 Mpro- (-)-epicatechin-3-O-gallate systems were found to be more stable than SARS-CoV-2 Mpro system. Further, (-)-epicatechin-3-O-gallate was subjected to QSAR analysis which predicted IC50 of 0.3281 nM against SARS-CoV-2 Mpro. Overall, (-)-epicatechin-3-O-gallate showed a potential binding affinity with SARS-CoV-2 Mpro and could be proposed as a potential natural compound for COVID-19 treatment.

Densitometric analysis of rep-PCR data: Insight into genetic variability and transmission of Clostridium perfringens typed with an improved multiplex PCR.

An epidemiological study was conducted in North-East India (part of Indo-Burma biodiversity hotspot) to better understand the distribution, diversity, and transmission of Clostridium perfringens among livestock, pets, wild animals (captive), and humans. A total of 160 C. perfringens isolates were recovered from 642 diarrhoeic faecal samples with an isolation rate of 24.92%. Isolation rate was the highest among captive wild animals (37.5%) followed by dog (34.6%), human (33.8%), pig (32.7%), cattle (20.8%), goat (18.3%) and poultry (9.3%). Isolates were toxin typed using a seven gene multiplex PCR designed for simultaneous detection of cpa, cpb, cpb2, etx, iap, cpe and netB. The majority of isolates, 128 (80%) were of type A, followed by 17 (10.62%), 5 (3.12%), 4 (2.5%), 3 (1.87%), 2 (1.25%) and 1 (0.63%) isolates of type C, D, E, G, F and B, respectively. Beta 2 toxin gene was present in 65 (50%) of type A isolates, followed by 7 (41.2%), 4 (80%), 1(25%), and 1 (100%) of type C, D, G and B isolates, respectively. Beta 2 toxin has a high prevalence among dogs (28.6%), cattle (27.3%), and pig (20.8%) compared to humans, goat, wild animals, and poultry (1.2-14.3%). The prevalence of CPE and NetB toxin-positive strains was low, with only 3 (1.8%) and 5 (3.1%) isolates, respectively. Association of C. perfringens with diarrhoea in Civet Cat, Golden Langur, and Gray Langur has been reported for the first time. The genetic diversity and transmission of isolates were investigated using automated rep-PCR (Diversilab®, bioMérieux) using two densitometry-based matrices: modified Kullback-Leibler (KL) and Pearson's correlation (PC). The PC and modified KL matrices formed three distinct clusters with 59% and 27.2% similarity, respectively. C. perfringens diversity and transmission were best studied using modified KL matrix that placed more emphasis on the presence of bands rather than intensity. However, the PC method was found to be more suitable for differentiating strains within a toxin type, with slightly higher D-values.

Fish gill microbiome from India's largest Brahmaputra River-a trans-border biodiversity hotspot region.

In this study, we sequenced the V3-V4 region of 16S rRNA gene amplicon using paired-end Illumina HiSeq to study the bacterial community in the gills of fish from the bank of the trans-border river of Brahmaputra, Northeast India. Metagenome data consisted of 278,784 reads, 248-bp length, and 56.48% GC content with 85% sequence having a Phred score Q = 30. Community metagenomics revealed a total of 631 genera belonging to 22 different phyla, dominated by Proteobacteria (118,222 features), Firmicutes (101,043 features), Actinobacteria (34,189 features), Bacteroidetes (17,977 features), and Cyanobacteria (2730 features). The bacterial community identified was composed of both pathogenic zoonotic and non-harmful groups. The pathway or functional analysis of the fish gill microbiome exhibited 21 different pathways which also included the pathogenic-related functions. Our data detected a wide group of bacterial communities that will be useful in further isolating and characterizing the pathogenic bacteria from the fish and also to understand the bacterial association in highly consumed fish.

Efficacy of Pulsed-Field Gel Electrophoresis and Repetitive Element Sequence-Based PCR in Typing of Salmonella Isolates from Assam, India.

A total of 12 Salmonella isolates belonging to different serovars, viz, Salmonella enterica serovar Enteritidis (n = 4), Salmonella enterica serovar Weltevreden (n = 4), Salmonella enterica serovar Newport (n = 1), Salmonella enterica serovar Litchifield (n = 1), and untypeable strains (n = 2) were isolated from 332 diarrheic fecal samples collected from animals, birds, and humans. Of the two molecular typing methods applied, viz, repetitive element sequence-based PCR (REP-PCR) and pulsed-field gel electrophoresis (PFGE), PFGE could clearly differentiate the strains belonging to different serovars as well as differentiate between strains of the same serovar with respect to their source of isolation, whereas REP-PCR could not differentiate between strains of the same serovar. Thus, it can be suggested that PFGE is more useful and appropriate for molecular typing of Salmonella isolates during epidemiological investigations than REP-PCR.

Sodium Phenylbutyrate and Edaravone Abrogate Chronic Restraint Stress-Induced Behavioral Deficits: Implication of Oxido-Nitrosative, Endoplasmic Reticulum Stress Cascade, and Neuroinflammation.

Chronic stress exposure can produce deleterious effects on the hippocampus (HC) which eventually leads to cognitive impairment and depression. Endoplasmic reticulum (ER) stress has been reported as one of the major culprits in the development of stress-induced cognitive impairment and depression. We investigated the neuroprotective efficacy of sodium phenylbutyrate (SPB), an ER stress inhibitor, and edaravone, a free radical scavenger, against chronic restraint stress (CRS)-induced cognitive deficits and anxiety- and depressive-like behavior in mice. Adult male Swiss albino mice were restrained for 6 h/day for 28 days and injected (i.p.) with SPB (40 and 120 mg/kg) or edaravone (3 and 10 mg/kg) for the last seven days. After stress cessation, the anxiety- and depressive-like behavior along with spatial learning and memory were examined. Furthermore, oxido-nitrosative stress, proinflammatory cytokines, and gene expression level of ER stress-related genes were assessed in HC and prefrontal cortex (PFC). CRS-exposed mice showed anxiety- and depressive-like behavior, which was significantly improved by SPB and edaravone treatment. In addition, SPB and edaravone treatment significantly alleviated CRS-induced spatial learning and memory impairment. Furthermore, CRS-evoked oxido-nitrosative stress, neuroinflammation, and depletion of Brain-derived neurotrophic factor were significantly ameliorated by SPB and edaravone treatment. We found significant up-regulation of ER stress-related genes in both HC and PFC regions, which were suppressed by SPB and edaravone treatment in CRS mice. Our study provides evidence that SPB and edaravone exerted neuroprotective effects on CRS-induced cognitive deficits and anxiety- and depressive-like behavior, which is possibly coupled with inhibition of oxido-nitrosative stress, neuroinflammation, and ER stress cascade.

A simplified multiplex PCR-based typing method for common Salmonella enterica serovars supported by online server-based detection system.

BACKGROUND & OBJECTIVES: A rapid and simple alternative method is needed to replace the laborious, time-consuming Salmonella serotyping. The objective of the present study was to improve and simplify a previously reported multiplex polymerase chain reaction (PCR)-based method and to create an online server to enable rapid determination of serovars. METHODS: A method of multiplex PCR-based genome typing (MPGT) was standardized using 59 Salmonella isolates of 31 serovars. Several previously reported primers were modified to obtain a more accurate performance. The screen was separated into four different multiplex reactions distinguishable on standard electrophoresis. A blind study was subsequently performed with 81 isolates of 10 serovars most prevalent in India. Whole genome information from 440 Salmonella isolates was used to confirm the usefulness of this method and concurrence of in silico predictions and PCR results were investigated. A public server (http://www.mpgt-salmonella.res.in) was established for data storage and determination of closest previously observed Salmonella isolates based on obtained MPGT patterns. RESULTS: The 16 target genes amplified showed variability in their presence in strains from different serotypes. Hence, identical amplification patterns suggested genetic relatedness of strains and usually identical serological behaviour. The observed absence/presence patterns of genes were converted to an MPGT code. Altogether, 83 different codes were predicted in silico based on the whole genome information of 440 strains. Results confirmed that major serovars usually displayed unique MPGT codes. INTERPRETATION & CONCLUSIONS: The multiplex PCR assay resulted in specific binary codes for isolates from each of the 31 Salmonella serovars tested. The online server allowed the user to compare obtained PCR results with stored previous patterns. Simplicity, speed and cost-effectiveness make this tool useful for quick outbreak management.

Polymorphism and nucleotide sequencing of BMPR1B gene in prolific Assam hill goat.

Assam hill goat (Capra hircus) is a prolific local goat in India. bone morphogenetic protein receptor (BMPR1B) gene was studied as a candidate gene for the prolificacy of goats. The objective of the present study was to detect the incidence of mutation in the exonic region of BMPR1B gene of Assam hill goat. Total 90 blood samples were collected randomly from different parts of Assam and genomic DNA were extracted using phenol-chloroform method. The quantity and quality of extracted DNA was examined by spectrophotometry and gel electrophoresis, respectively. PCR amplicon showed a product of 140 bp fragment of BMPR1B gene. The purified product upon digestion with AvaII showed monomorphic banding pattern and revealed wild type alleles with AA genotype. Nucleotide sequencing showed one new mutation 773 (G→C) which is found to be unique in Assam hill goat. Construction of tree at nucleotide level generates from the present experiment lies in common cluster which differs from the other breeds of goat. The analysis of polymorphism for BMPR1B in Assam hill goat indicates that the genetic factor responsible for prolificacy or multiple kidding rates is not related to the reported mutated alleles of BMPR1B gene. Therefore, attempts to be made to detect other SNPs for BMPR1B gene or otherwise effort should be made towards other fecundity gene which might be responsible for the prolificacy of Assam hill goat.

Computational approaches for evaluation of isobavachin as potential inhibitor against t877a and w741l mutations in prostate cancer.

Prostate cancer is the World's second most common cancer, with the fifth-highest male mortality rate. Point mutations such as T877A and W741L are frequently seen in advanced prostate cancer patients, conferring drug-resistance and hence driving cancer growth. Such occurrence of drug resistance in prostate cancer necessitates designing of suitable ligands to ensure better interactions with the receptors which can block the progression of the disease. The present study focus on the modification of plant-derived flavonoids that might act as inhibitors against such point mutations namely, T877A and W741L. In T877A mutation threonine is substituted by alanine at the 877 codon and W741L mutation, tryptophan is substituted by lysine at the 741 codon in prostate cancer. The study revolved on the aspect of the evaluation of Isobavachin and its derivatives as a potential agent to tackle such point mutations by using the in silico approach. A total of 98 molecular dockings were performed to find the ligand-receptor complexes with the lowest binding energy employing Autodock Software to conduct the blind and site-specific docking. Additionally, ligands were screened for Drug-likeness and toxicity using several tools yielding eight possible drug candidates. Based on the results of Molecular Docking, Drug-likeness, and ADMET testing, ten structures, including six complexes and three receptors were subjected to molecular dynamics simulation of 100 ns covering RMSD, RMSF, Rg, and MM/PBSA. Based on the simulation results, Isobavachin, IsoMod4, and IsoMod7 were concluded to be stable and exhibited potential properties for developing a novel drug to combat prostate cancer and its associated drug-resistance.Communicated by Ramaswamy H. Sarma.

Evaluation of Pathogenicity and Structural Alterations for the Mutations Identified in the Conserved Region of the C-Terminal Kinase Domain of Human-Ribosomal S6 Kinase 1.

Human-ribosomal s6 kinase 1 (h-RSK1) is an effector kinase of the Ras/MAPK signaling pathway, which is involved in the regulation of the cell cycle, proliferation, and survival. RSKs comprise two functionally distinct kinase domains at the N-terminal (NTKD) and C-terminal (CTKD) separated by a linker region. The mutations in RSK1 may have the potential to provide an extra benefit to the cancer cell to proliferate, migrate, and survive. The present study focuses on evaluating the structural basis for the missense mutations identified at the C-terminal kinase domain of human-RSK1. A total of 139 mutations reported on RSK1 were retrieved from cBioPortal, where 62 were located at the CTKD region. Furthermore, 10 missense mutations Arg434Pro, Thr701Met, Ala704Thr, Arg725Trp, Arg726Gln, His533Asn, Pro613Leu, Ser720Cys, Arg725Gln, and Ser732Phe were predicted to be deleterious using in silico tools. To our observation, these mutations are located in the evolutionarily conserved region of RSK1 and shown to alter the inter- and intramolecular interactions and also the conformational stability of RSK1-CTKD. The molecular dynamics (MD) simulation study further revealed that the five mutations Arg434Pro, Thr701Met, Ala704Thr, Arg725Trp, and Arg726Gln showed maximum structural alterations in RSK1-CTKD. Thus, based on the in silico and MD simulation analysis, it can be concluded that the reported mutations may serve as potential candidates for further functional studies.

Phytocompounds from Phyllanthus acidus (L.) Skeels in the management of Monkeypox Virus infections.

Monkeypox is a communicable disease similar to smallpox, primarily occurring in African countries. However, recently it has spread to countries outside Africa and may arise as the next threat after COVID-pandemic. The causative organism, i.e. Monkeypox Virus (MPV) spreads from one individual to another primarily through inhalation of respiratory droplets or through contact with skin lesions of infected individuals. No known drugs are available specifically for MPV. Due to its similarity with smallpox, treatment of monkeypox is being attempted through the administration of the smallpox vaccine. Therefore, we evaluated the efficacy of the plant Phyllanthus acidus against MPV since it is traditionally used in the treatment of chickenpox and smallpox. Through functional annotation, PASS prediction and Network pharmacology analysis, the effectiveness of these chosen P. acidus-derived phytocompounds against MPV was confirmed. Target prediction of the phytocompounds identified in GC-MS analysis of the plant extract showed them to be associated with 76 human proteins. The compounds also show good binding affinity with selected viral proteins: DNA polymerase (DNApol), Putative Virulence Factor (vPVF) and Cytokine Binding Protein. Prediction of Activity Spectra for Substances (PASS) and functional annotation of the target proteins further support their antiviral nature through interaction with these proteins. The compounds were found to modulate pathways related to symptoms of viral infection and this may help in maintaining homeostasis. Our study demonstrates antiviral activity as well as the therapeutic potential of the plant against MPV infection.Communicated by Ramaswamy H. Sarma.

Development of recombinant subunit vaccine targeting InvH protein of Salmonella Typhimurium and evaluation of its immunoprotective efficacy against salmonellosis.

Salmonella Typhimurium is the most prevalent non-host specific Salmonella serovars and a major concern for both human and animal health systems worldwide contributing to significant economic loss. Type 3 secretion system (T3SS) of Salmonella plays an important role in bacterial adherence and entry into the host epithelial cells. The product of invH gene of Salmonella is an important component of the needle complex of the type 3 secretion system. Hence, the present study was undertaken to clone and express the 15 kDa InvH surface protein of Salmonella Typhimurium in an E. coli host and to evaluate its immune potency in mice. The purified recombinant InvH (r-InvH) protein provoked a significant (p < 0.01) rise in IgG in the inoculated mice. The immunized mice were completely (100%) protected against the challenge dose of 107.5 LD50, while protection against challenge with the same dose of heterologous serovars was 90%. The bacterin-vaccinated group showed homologous protection of 60% against all three serovars. Findings in this study suggest the potential of the r-InvH protein of S. Typhimurium as an effective vaccine candidate against Salmonella infections.

Immunopotential of Pasteurella multocida bivalent outer membrane protein-based vaccine entrapped in aluminum hydroxide nanoparticles.

Swine pasteurellosis is one of the most economically important diseases of pig caused by Pasteurella multocida (P. multocida) capsular types A and D. These organisms are commensals and opportunistic pathogens in the upper respiratory tract in pig. In the present study, we extracted whole outer membrane proteins (OMP) from P. multocida capsular types A and D and were mixed together in the ratio of 1:1 forming bivalent outer-membrane proteins. The bivalent OMP was adsorbed onto aluminum hydroxide nanoparticles. The size of aluminum hydroxide nanoparticles adsorbed outer membrane protein was found to be in the range of 125 to 130 nm. We observed that aluminum hydroxide nanoparticles adjuvanted bivalent OMP-based vaccine elicited quicker immune kinetics in terms of IgG response as compared to aluminum hydroxide microparticles adjuvanted bivalent bacterin vaccine against P. multocida capsular type A and D.

Prevalence, antimicrobial resistance and virulence genes of Salmonella serovars isolated from humans and animals.

We investigated the prevalence, antimicrobial susceptibility, antimicrobial resistance and virulence genes of Salmonella isolates recovered from humans and different species of animals. Out of 1231 samples, 88 (7.15%) Salmonella isolates were obtained, among which 21 (23.86%) belonged to Salmonella enterica subsp. enterica sero var. Weltevreden, 22 (25%) to S. Enteritidis, 16 (18.2%) to S. Typhi and 14 (15.9%) to S. Newport; 7 (7.95%) isolates were untypable. Among the 88 isolates, 65.90% showed resistance to gentamicin, 61.36% to tetracycline, 61.18% to cefotaxime, 48.86% to trimethoprim, 45.45% to ampicillin, 11.36% to ceftriaxone, 10.22% to chloramphenicol and 7.95% each to ciprofloxacin and cefepime. Most of the isolates were susceptible, with a low MIC (≤ 0.25 µg/ml) value, to cefepime, cefotaxime, ciprofloxacin, ceftriaxone and co-trimoxazole and with a moderate MIC (0.5-4 µg/ml) to ampicillin, tetracycline, gentamicin and chloramphenicol. The resistance genes blaTEM, tetA and dfrA12 were most prevalent, irrespective of the host of origin of the isolates. While invA was used for molecular detection of Salmonella, other virulence genes, viz. sipA, sipB, sipC, stn and pagN, were also detected in all Salmonella isolates. A total of 38.64% isolates were multidrug-resistant (MDR), and various virulence genes were present among the isolated serovars. This study highlights the importance of continuous monitoring and surveillance for pathogenic Salmonella and their potential risks to both humans and animals.

Draft Genome Sequence Analysis of the Genotype II African Swine Fever Virus from India.

African swine fever virus (ASFV) entered the northeastern (NE) part of India early in 2020, causing huge economic loss to the piggery sector. Here, we are presenting a brief report on the draft genome sequence of an ASFV strain ABTCVSCK_ASF007 from Assam state of NE India belonging to genotype II.

Potential anti-viral activity of approved repurposed drug against main protease of SARS-CoV-2: an in silico based approach.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which was first reported in Wuhan province of China, has become a deadly pandemic causing alarmingly high morbidity and mortality. In the absence of new targeted drugs and vaccines against SARS-CoV-2 at present, the choices for effective treatments are limited. Therefore, considering the exigency of the situation, we focused on identifying the available approved drugs as potential inhibitor against the promising Coronavirus drug target, the Main Protease, using computer-aided methods. We created a library of U. S. Food and Drug Administration approved anti-microbial drugs and virtually screened it against the available crystal structures of Main Protease of the virus. The study revealed that Viomycin showed the highest -CDocker energy after docking at the active site of SARS-CoV-2 Main Protease. It is noteworthy that Viomycin showed higher -CDocker energy as compared to the drugs currently under clinical trial for SARS-CoV-2 treatment viz. Ritonavir and Lopinavir. Additionally, Viomycin formed higher number of H-bonds with SARS-CoV-2 Main Protease than its co-crystallised inhibitor compound N3. Molecular dynamics simulation further showed that Viomycin embedded deeply inside the binding pocket and formed robust binding with SARS-CoV-2 Main Protease. Therefore, we propose that Viomycin may act as a potential inhibitor of the Main Protease of SARS-CoV-2. Further optimisations with the drug may support the much-needed rapid response to mitigate the pandemic.Communicated by Ramaswamy H. Sarma.

Antinociceptive activity of methanolic extract of leaves of Achyranthes aspera Linn. (Amaranthaceae) in animal models of nociception.

Antinociceptive activity of methanolic extract of leaves of A. aspera was studied by peripheral/non-narcotic model of nociception like acetic acid induced writhing syndrome test and central/narcotic models like hot plate and tail flick tests. The methanolic extract of the plant, administered orally (@ 300, 600 and 900 mg/kg, body weight) and the standard drug (piroxicam; 10 mg/kg body weight, po) produced significant analgesic activity in acetic acid induced writhing syndrome as compared to the vehicle treated control group. In the hot plate analgesic test, in A. aspera at the above doses and the standard drug treated group (morphine sulphate @ 1.5 mg/kg, ip), the duration of reaction time (sec) increased dose dependently and significantly compared to the control group. In the tail flick test, the plant extract produced dose dependant increase in reaction time which was significantly higher in the test and standard group compared to the control group. The plant possesses significant antinociceptive property as evidenced in all the animal models of nociception. It might possibly exert its effect through diverse mechanism that may involve both central and peripheral pathways. The preliminary phytochemical investigation revealed the presence of steroids, alkaloids and triterpene in the methanolic extract of leaves of A. aspera which may be responsible for its antinociceptive activity.

Analysis of codon usage of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) and its adaptability in dog.

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is recognized as one of the life-threatening viruses causing the most destructive pandemic in this century. The genesis of this virus is still unknown. To elucidate its molecular evolution and regulation of gene expression, the knowledge of codon usage is a pre-requisite. In this study, an attempt was made to document the genome-wide codon usage profile and the various factors influencing the codon usage patterns of SARS-CoV-2 in human and dog. The SARS-CoV-2 genome showed relative abundance of A and U nucleotides and relative synonymous codon usage analysis revealed that the preferred synonymous codons mostly end with A/U. The analysis of ENc-GC3s, Neutrality and Parity rule 2 plots indicated that natural selection and other undefined factors dominate the overall codon usage bias in SARS-CoV-2 whereas the impact of mutation pressure is comparatively minor. The codon adaptation index and relative codon deoptimization index of SARS-CoV-2 deciphered that human is more favoured host for adaptation compared to dog. These results enhance our understanding of the factors involved in evolution of the novel human SARS-CoV-2 and its adaptability in dog.