A benzimidazole scaffold as a promising inhibitor against SARS-CoV-2.

The manuscript reports the green-chemical synthesis of a new diindole-substituted benzimidazole compound, B1 through a straightforward route in coupling between indolyl-3-carboxaldehyde and o-phenylenediamine in water medium under the aerobic condition at 75 ºC. The single crystal X-ray structural analysis of B1 suggests that the disubstituted benzimidazole compound crystallizes in a monoclinic system and the indole groups exist in a perpendicular fashion with respect to benzimidazole moiety. The SARS-CoV-2 screening activity has been studied against 1 × 10e4 VeroE6 cells in a dose-dependent manner following Hoechst 33342 and nucleocapsid staining activity with respect to remdesivir. The compound exhibits 92.4% cell viability for 30 h and 35.1% inhibition against VeroE6 cells at non-cytotoxic concentration. Molecular docking studies predict high binding propensities of B1 with the main protease (Mpro) and non-structural (nsp2 and nsp7-nsp8) proteins of SARS-CoV-2 through a number of non-covalent interactions. Molecular dynamics (MD) simulation analysis for 100 ns confirms the formation of stable conformations of B1-docked proteins with significant changes of binding energy, attributing the potential inhibition properties of the synthetic benzimidazole scaffold against SARS-CoV-2. Communicated by Ramaswamy H. Sarma.

Mechanisms of Antimicrobial Resistance: Highlights on Current Advance Methods for Detection of Drug Resistance and Current Pipeline Antitubercular Agents.

BACKGROUND: Sir Alexander Fleming accidentally discovered antibiotics in 1928. Antibiotics have played a significant role in treating infectious diseases. The extensive use of antibiotics has enabled the microorganisms to develop resistance against the antibiotics given, which has become a global concern. This review aims to examine some of the mechanisms behind resistance and advanced methods for detecting drug-resistant and antibacterial drugs in the clinical pipeline. METHODS: An extensive search was carried out in different databases, viz. Scopus, Embase, Cochrane, and PubMed. The keywords used in the search were antimicrobial resistance, antibiotic resistance, antimicrobial tolerance, antibiotic tolerance, and methods to reduce antimicrobial resistance. All the studies published in the English language and studies focusing on antibiotic resistance were included in the analysis. RESULTS: The most common mechanisms involved in antimicrobial resistance are reflux pumping, antibiotic inactivation, acquired resistance, intrinsic resistance, mutation, bio-film resistance, etc. Antibacterial medicinal products for multidrug resistance (MDR) infections are active against pathogens, which are registered in the World Health Organization (WHO) priority pathogen list (PPL). CONCLUSION: Furthermore, their innovativeness was assessed by their lack of cross-resistance. Finally, novel antibacterial drugs without pre-existing inter-resistance, especially those with highresistance gram-negative bacteria and tuberculosis (TB), are understated and urgently required.

A hydrated 2,3-diaminophenazinium chloride as a promising building block against SARS-CoV-2.

Phenazine scaffolds are the versatile secondary metabolites of bacterial origin. It functions in the biological control of plant pathogens and contributes to the producing strains ecological fitness and pathogenicity. In the light of the excellent therapeutic properties of phenazine, we have synthesized a hydrated 2,3-diaminophenazinium chloride (DAPH+Cl-·3H2O) through direct catalytic oxidation of o-phenylenediamine with an iron(III) complex, [Fe(1,10-phenanthroline)2Cl2]NO3 in ethanol under aerobic condition. The crystal structure, molecular complexity and supramolecular aspects of DAPH+Cl- were confirmed and elucidated with different spectroscopic methods and single crystal X-ray structural analysis. Crystal engineering study on DAPH+Cl- exhibits a fascinating formation of (H2O)2…Cl-…(H2O) cluster and energy framework analysis of defines the role of chloride ions in the stabilization of DAPH+Cl-. The bactericidal efficiency of the compound has been testified against few clinical bacteria like Streptococcus pneumoniae, Escherichia coli, K. pneumoniae using the disc diffusion method and the results of high inhibition zone suggest its excellent antibacterial properties. The phenazinium chloride exhibits a significant percentage of cell viability and a considerable inhibition property against SARS-CoV-2 at non-cytotoxic concentration compared to remdesivir. Molecular docking studies estimate a good binding propensity of DAPH+Cl- with non-structural proteins (nsp2 and nsp7-nsp-8) and the main protease (Mpro) of SARS-CoV-2. The molecular dynamics simulation studies attribute the conformationally stable structures of the DAPH+Cl- bound Mpro and nsp2, nsp7-nsp8 complexes as evident from the considerable binding energy values, - 19.2 ± 0.3, - 25.7 ± 0.1, and - 24.5 ± 0.7 kcal/mol, respectively.

Biologically Active Antimicrobial Compounds from Marine Microorganisms (2005-2019).

INTRODUCTION: The increase in contagious diseases like nosocomial infections, urinary tract infections, and meningitis has led to the emergence of antimicrobial resistance urgently needs new antimicrobial medication with new modes of action. Some of the antibiotics present in the market have been obtained from terrestrial plants, or extracted semisynthetically from materials which can be fermented. METHODS: Marine microorganisms account for approximately 80% of sea biomass. They are essential for the survival and well-being of aquatic habitats due to their indispensable contribution to biogeochemical cycles and biological processes. In marine ecosystems, microorganisms live as microbial communities in seawater, where symbiotic relationships are formed, and their ecological functions are fulfilled. RESULTS: Marine microorganisms remain the largest, most diverse and most exciting source of structurally and functionally complex antimicrobial agents. They are extremely involved in their structure and functions. Enormous biological wealth lies in marine habitats. These microorganisms are potential sources of novel antimicrobial compounds to combat the most infectious diseases like nosocomial infections, and urinary tract infections. CONCLUSION: This study deals with biologically active antimicrobial compounds taken from marine microorganism source, which was reported between the years 2005 and 2019. This review highlights their chemical groups, their bioactivities and sources. Marine microorganism exploitation techniques have also been reported by the authors.