Reverse transcriptase and integrase are key enzymes that play a pivotal role in HIV-1 viral maturation and replication. Reverse transcriptase consists of two active sites: RNA-dependent DNA polymerase and RNase H. The catalytic domains of integrase and RNase H share striking similarity, comprising two aspartates and one glutamate residue, also known as the catalytic DDE triad, and a Mg2+ pair. The simultaneous inhibition of reverse transcriptase and integrase can be a rational drug discovery approach for combating the emerging drug resistance problem. In the present review, the dual inhibition of RNase H and integrase is systematically discussed, including rationality of design, journey of development, advancement and future perspective.
β-Carboline, a naturally occurring indole alkaloid, holds a momentous spot in the field of medicinal chemistry due to its myriad of pharmacological actions like anticancer, antiviral, antibacterial, antifungal, antileishmanial, antimalarial, neuropharmacological, anti-inflammatory and antithrombotic among others. β-Carbolines exhibit their pharmacological activity via diverse mechanisms. This review provides a recent update (2015-2020) on the anti-infective potential of natural and synthetic β-carboline analogs focusing on its antibacterial, antifungal, antiviral, antimalarial, antileishmanial and antitrypanosomal properties. In cases where enough details are available, a note on its mechanism of action is also added.
COVID-19 caused by the novel SARS-CoV-2 has been declared a pandemic by the WHO is causing havoc across the entire world. As of May end, about 6 million people have been affected, and 367 166 have died from COVID-19. Recent studies suggest that the SARS-CoV-2 genome shares about 80% similarity with the SARS-CoV-1 while their protein RNA dependent RNA polymerase (RdRp) shares 96% sequence similarity. Remdesivir, an RdRp inhibitor, exhibited potent activity against SARS-CoV-2 in vitro. 3-Chymotrypsin like protease (also known as Mpro) and papain-like protease, have emerged as the potential therapeutic targets for drug discovery against coronaviruses owing to their crucial role in viral entry and host-cell invasion. Crystal structures of therapeutically important SARS-CoV-2 target proteins, namely, RdRp, Mpro, endoribonuclease Nsp15/NendoU and receptor binding domain of CoV-2 spike protein has been resolved, which have facilitated the structure-based design and discovery of new inhibitors. Furthermore, studies have indicated that the spike proteins of SARS-CoV-2 use the Angiotensin Converting Enzyme-2 (ACE-2) receptor for its attachment similar to SARS-CoV-1, which is followed by priming of spike protein by Transmembrane protease serine 2 (TMPRSS2) which can be targeted by a proven inhibitor of TMPRSS2, camostat. The current treatment strategy includes repurposing of existing drugs that were found to be effective against other RNA viruses like SARS, MERS, and Ebola. This review presents a critical analysis of druggable targets of SARS CoV-2, new drug discovery, development, and treatment opportunities for COVID-19.
A diverse group of rhizobacteria persists in the rhizospheric soil, on the surface of roots, or in association with rice plants. These bacteria colonize plant root systems, enhance plant growth and crop yield. Indigenous rhizobacteria are known to promote soil health, grain production quality and serve as sustainable bioinoculant. The present study was aimed to isolate, identify and characterize indigenous plant growth promoting (PGP) diazotrophic bacteria associated with the rhizosphere of rice fields from different areas of Jammu and Kashmir, India. A total of 15 bacteria were isolated and evaluated for various PGP traits, antagonistic activity against phytopathogens, production of hydrolytic enzymes and biofilm formation under in-vitro conditions. The majority of the isolated bacteria were Gram-negative. Out of 15 bacterial isolates, nine isolates produced IAA (12.24 ± 2.86 to 250.3 ± 1.15 μg/ml), 6 isolates exhibited phosphate solubilization activity (36.69 ± 1.63 to 312.4 ± 1.15 μg/ml), 7 isolates exhibited rock phosphate solubilization while 5 isolates solubilized zinc (10-18 mm), 7 isolates showed siderophore production, 8 isolates exhibited HCN production, 6 isolates exhibited aminocyclopropane-1-carboxylate (ACC) deaminase activity, 13 isolates exhibited cellulase activity, nine isolates exhibited amylase and lipase activity and six isolates exhibited chitinase activity. In addition, 5 isolates showed amplification with the nifH gene and showed a significant amount of nitrogenase activity in a range of 0.127-4.39 μmol C2H4/mg protein/h. Five isolates viz., IHK-1, IHK-3, IHK-13, IHK-15 and IHK-25 exhibited most PGP attributes and successfully limited the mycelial growth of Rhizoctonia solani and Fusarium oxysporum in-vitro. All the five bacterial isolates were identified based on morphological, biochemical and 16S rDNA gene sequencing study, as Stenotrophomonas maltophilia, Enterobacter sp., Bacillus sp., Ochrobactrum haematophilum and Pseudomonas aeruginosa. Rice plants developed from seeds inoculated with these PGP strains individually had considerably higher germination percentage, seed vigor index and total dry biomass when compared to control. These findings strongly imply that the PGP diazotrophic bacteria identified in this work could be employed as plant growth stimulators in rice.