Evolving geographic diversity in SARS-CoV2 and in silico analysis of replicating enzyme 3CLpro targeting repurposed drug candidates.

BACKGROUND: Severe acute respiratory syndrome (SARS) has been initiating pandemics since the beginning of the century. In December 2019, the world was hit again by a devastating SARS episode that has so far infected almost four million individuals worldwide, with over 200,000 fatalities having already occurred by mid-April 2020, and the infection rate continues to grow exponentially. SARS coronavirus 2 (SARS-CoV-2) is a single stranded RNA pathogen which is characterised by a high mutation rate. It is vital to explore the mutagenic capability of the viral genome that enables SARS-CoV-2 to rapidly jump from one host immunity to another and adapt to the genetic pool of local populations. METHODS: For this study, we analysed 2301 complete viral sequences reported from SARS-CoV-2 infected patients. SARS-CoV-2 host genomes were collected from The Global Initiative on Sharing All Influenza Data (GISAID) database containing 9 genomes from pangolin-CoV origin and 3 genomes from bat-CoV origin, Wuhan SARS-CoV2 reference genome was collected from GeneBank database. The Multiple sequence alignment tool, Clustal Omega was used for genomic sequence alignment. The viral replicating enzyme, 3-chymotrypsin-like cysteine protease (3CLpro) that plays a key role in its pathogenicity was used to assess its affinity with pharmacological inhibitors and repurposed drugs such as anti-viral flavones, biflavanoids, anti-malarial drugs and vitamin supplements. RESULTS: Our results demonstrate that bat-CoV shares > 96% similar identity, while pangolin-CoV shares 85.98% identity with Wuhan SARS-CoV-2 genome. This in-depth analysis has identified 12 novel recurrent mutations in South American and African viral genomes out of which 3 were unique in South America, 4 unique in Africa and 5 were present in-patient isolates from both populations. Using state of the art in silico approaches, this study further investigates the interaction of repurposed drugs with the SARS-CoV-2 3CLpro enzyme, which regulates viral replication machinery. CONCLUSIONS: Overall, this study provides insights into the evolving mutations, with implications to understand viral pathogenicity and possible new strategies for repurposing compounds to combat the nCovid-19 pandemic.

Hepatoprotective effect of Aloe vera against cartap- and malathion-induced toxicity in Wistar rats.

Exposure to mixture of pesticides in agricultural practices pose a serious threat to the nontarget animals. In present work, we have evaluated the synergistic effect of cartap and malathion on rat liver followed by impact of Aloe vera leaves aqueous extract, which is not known. The animals in eight groups were used; each containing six rats: Group 1 acted as a control, Group 2-control with A. vera leaves aqueous extract, Group 3-with cartap, Group 4-with malathion, Group 5-with mixture of cartap and malathion, Group 6-cartap with the pretreatment of A. vera leaf extract, Group 7-malathion with the pretreatment of A. vera leaf extract, Group 8-mixture of cartap and malathion with the pretreatment of A. vera leaf extract . The animals treated for 15 days were killed after 24hr of last treatment. The biochemical studies in the rat liver demonstrated significant perturbations in the levels of nonenzymatic (glutathione and malondialdehyde) and enzymatic (superoxide dismutase, catalase, and glutathione- S-transferase) antioxidative indices. The histopathological examination of liver revealed serious congestion in central vein and the disorganization of hepatic cords due to pesticide treatment. The administration of A. vera leaves aqueous extract was able to markedly protect rat liver from the pesticides-induced toxicity. The data indicated that pesticides were able to significantly induce oxidative stress which was substantially reduced by the application of plant extract .

Camphor sulphonic acid mediated quantitative 1,3-diol protection of major Labdane diterpenes isolated from Andrographis paniculata.

Phytochemical survey of the methanol extract of the dried aerial parts of Andrographis paniculata led to the isolation of major labdane diterpenes, namely 14-deoxy-11,12-didehydroandrographolide, andrographolide and neoandrographolide. Andrographolide was found to be the major phytoconstituent of the plant which was biologically active. For better physiochemical characteristics and bioefficacy, andrographolide is subjected to semi-synthetic modifications. However, presence of several free hydroxyl groups associated with this molecule make it quite polar and poorly soluble in many organic solvents and hence unsuitable for synthetic modifications. One way of resolving its solubility issue is to protect 1,3-diol quantitatively under mild reaction condition without effecting other functional groups. Reaction conditions were optimised using different solvent systems and catalysts towards this direction. X-ray structure of 3,19-isopropylidene-14-deoxy-11,12-didehydroandrographolide is being reported here for the first time. Isolated compounds and derivatives were confirmed by spectral analysis or X-ray data analysis.

Anti-tuberculosis activity of Indian grass KHUS (Vetiveria zizanioides L. Nash).

AIMS & OBJECTIVES: Vetiveria zizanioides L. Nash (Family: Poaceae) root (intact and spent) extracts and fractions were evaluated for antimycobacterial activity against Mycobacterium tuberculosis H(37)Rv and H(37)Ra strains using radiometric BACTEC 460 TB system. METHODS & RESULTS: The ethanolic extract of intact as well as spent root were showed potent antituberculosis activity at a minimum concentration of 500µg/mL. The hexane fraction also showed antibacterial action by recording continuous decline in growth index (GI) of M. tuberculosis at 50µg/mL. It was furthermore observed that root extract and hexane fraction showed activity even after the extraction of essential oil by hydro-distillation. CONCLUSION: Our results suggest that ethanolic extract and hexane fraction exhibited potent antimycobacterial activity. SIGNIFICANCE AND IMPACT OF THE STUDY: The observed potential inhibitory characteristic not only supports the traditional medicinal uses of vetiver but also signify a promising candidature of root extract and hexane fraction of V. zizanioides as an antituberculosis agent.

Antifungal activity of Glycyrrhiza glabra extracts and its active constituent glabridin.

Glabridin, an active constituent of Glycyrrhiza glabra roots, was found to be active against both yeast and filamentous fungi. Glabridin also showed resistance modifying activity against drug resistant mutants of Candida albicans at a minimum inhibitory concentration of 31.25-250 microg/mL. Although the compound was reported earlier to be active against Candida albicans, but this is the first report of its activity against drug resistant mutants.

Antimicrobial potential of Glycyrrhiza glabra roots.

The present study was aimed to investigate antimicrobial potential of Glycyrrhiza glabra roots. Antimycobacterial activity of Glycyrrhiza glabra was found at 500 microg/mL concentration. Bioactivity guided phytochemical analysis identified glabridin as potentially active against both Mycobacterium tuberculosis H(37)Ra and H(37)Rv strains at 29.16 microg/mL concentration. It exhibited antimicrobial activity against both Gram-positive and Gram-negative bacteria. Our results indicate potential use of licorice as antitubercular agent through systemic experiments and sophisticated anti-TB assay.