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SARS-CoV-2 is an RNA coronavirus responsible for Acute Respiratory Syndrome (COVID-19). In January 2021, the re-occurrence of COVID-19 infection was at its peak, considered the second wave of epidemics. In the initial stage, it was considered a double mutant strain due to two significant mutations observed in their Spike protein (E484Q and L452R). Although it was first detected in India later on, it was spread to several countries worldwide, causing high fatality due to this strain. In the present study, we investigated the spreading of B.1.617 strain worldwide through 822 genome sequences submitted in GISAID on 21 April 2021. All genome sequences were analyzed for variations in genome sequences based on their effects due to changes in nucleotides. At Allele frequency 0.05, there were a total of 47 variations in ORF1ab, 22 in Spike protein gene, 6 variations in N gene, 5 in ORF8 and M gene, four mutations in Orf7a, and one nucleotide substitution observed for ORF3a, ORF6 and ORF7b gene. The clustering for similar mutations mentioned B.1.617 sub-lineages. The outcome of this study established relative occurrence and spread worldwide. The study’s finding represented that “double mutant” strain is not only spread through traveling but it is also observed to evolve naturally with different mutations observed in B.1.617 lineage. The information extracted from the study helps to understand viral evolution and genome variations of B.1.617 lineage. The results support the need of separating B.1.617 into sub-lineages.

Pneumonia of unknown cause detected in Wuhan, China was first reported to the WHO Country Office in China on 31 December 2019. The outbreak was declared a Public Health Emergency of International Concern on 30 January 2020. Currently, there is no Vaccine against COVID-19 pandemic and infection is spreading worldwide vary rapidly there is an exigent requirement of practicable drug treatment. Drug repurposing is one of the most promising approaches for that. Many reports are available with in silico drug repurposing but the majority of them engrossed on a single target. The present study aimed at screening the approved against Covid19 protein and extract the combination of operational comprehensively. A total of 1735 drug molecules against all COVID19 protein structures and sequential screening recognize the better potential of anti-HCV drugs over anti-HIV drugs. The study designated Elbasvir, Ledipasvir, Paritaprevir, Velpatasvir, Antrafenine Ergotamin as promising drug candidates for covid19 treatment. The computational analysis also reveled the better potential of proposed drugs over the currently used drug combination for COVID19 drugs.

Two novel 4-acylhydrazone-5-pyrazolones (L1=(Z)-N'-((4-chlorophenyl)(3-methyl-5-oxo-1-(p-tolyl)-4,5-dihydro-1H-pyrazol-4-yl)methylene)benzohydrazide and L2 = (Z)-N'-((4-chloro phenyl )(1-(3-chlorophenyl)-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-4-yl)methylene)benzohydrazide) were synthesized from 4-acyl-5-pyrazolone and benzoyl hydrazide and assessed for in silico and in vitro antimalarial activity. Synthesized one binary Zinc(II) complex 1 [Zn(L1)2]from L1. Two mixed ligands complexes 2 [Zn(L2)(bpy)(OAc)]EtOH and 3 [Zn(L2)(phen)(H2O)] were synthesized from L2 with 2,2’-bipyridine and 1, 10-phenanthroline, respectively. Ligands and complexes were characterized by 1H NMR, FT-IR, UV-Vis, Single crystal X-ray diffraction and conductance measurement. All compounds displayed decent outcomes in invitro antimalarial activity.

Two novel 4-acylhydrazone-5-pyrazolones (L1=(Z)-N'-((4-chlorophenyl)(3-methyl-5-oxo-1-(p-tolyl)-4,5-dihydro-1H-pyrazol-4-yl)methylene)benzohydrazide and L2 = (Z)-N'-((4-chlorophenyl)(1-(3-chlorophenyl)-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-4-yl)methylene)benzohydrazide) were synthesized from 4-acyl-5-pyrazolone and benzoyl hydrazide and assessed for in silico and in vitro antimalarial activity. One binary zinc(II) complex 1 [Zn(L1)2]DMF was synthesized from L1. Two mixed ligands complexes 2 [Zn(L2)(bpy)(OAc)]EtOH and 3 [Zn(L2)(phen)(H2O)] were synthesized from L2 with 2,2′-bipyridine and 1, 10-phenanthroline respectively. Ligands and complexes were characterized by 1H NMR, FT-IR, UV-Vis, Single crystal X-ray diffraction and conductance measurement. All compounds displayed decent outcomes in in vitro antimalarial activity.

Acute liver injury is frequently associated with oxidative stress. Here, we investigated the therapeutic potential of carbon monoxide releasing molecule A-1 (CORM A-1) in oxidative stress-mediated liver injury. Overnight-fasted mice were injected with acetaminophen (APAP; 300 mg/kg; intraperitoneally) and were sacrificed at 4 and 12 h. They showed elevated levels of serum transaminases, depleted hepatic glutathione (GSH) and hepatocyte necrosis. Mice injected with CORM A-1 (20 mg/kg) 1 h after APAP administration, had reduced serum transaminases, preserved hepatic GSH and reduced hepatocyte necrosis. Mice that received a lethal dose of APAP (600 mg/kg), died by 10 h; but those co-treated with CORM A-1 showed a 50% survival. Compared to APAP-treated mice, livers from those co-treated with CORM A-1, had upregulation of Nrf2 and ARE genes (HO-1, GCLM and NQO-1). APAP-treated mice had elevated hepatic mRNA levels of inflammatory genes (Nf-κB, TNF-α, IL1-β and IL-6), an effect blunted in those co-treated with CORM A-1. In tert-butyl hydroperoxide (t-BHP)-treated HepG2 cells, CORM A-1 augmented cell viability, reduced oxidative stress, activated the nuclear factor erythroid 2–related factor 2 (Nrf2) and anti-oxidant response element (ARE) genes. The molecular docking profile of CO in the kelch domain of Keap1 protein suggested that CO released from CORM A-1 mediated Nrf2 activation. Collectively, these data indicate that CORM A-1 reduces oxidative stress by upregulating Nrf2 and related genes, and restoring hepatic GSH, to reduce hepatocyte necrosis and thus minimize liver injury that contributes to an overall improved survival rate.

A decade since the availability of Mycobacterium tuberculosis (Mtb) genome sequence, no promising drug has seen the light of the day. This not only indicates the challenges in discovering new drugs but also suggests a gap in our current understanding of Mtb biology. We attempt to bridge this gap by carrying out extensive re-annotation and constructing a systems level protein interaction map of Mtb with an objective of finding novel drug target candidates. Towards this, we synergized crowd sourcing and social networking methods through an initiative `Connect to Decode' (C2D) to generate the first and largest manually curated interactome of Mtb termed `3interactome pathway' (IPW), encompassing a total of 1434 proteins connected through 2575 functional relationships. Interactions leading to gene regulation, signal transduction, metabolism, structural complex formation have been catalogued. In the process, we have functionally annotated 87% of the Mtb genome in context of gene products. We further combine IPW with STRING based network to report central proteins, which may be assessed as potential drug targets for development of drugs with least possible side effects. The fact that five of the 17 predicted drug targets are already experimentally validated either genetically or biochemically lends credence to our unique approach.