Computational Design of Novel Griseofulvin Derivatives Demonstrating Potential Antibacterial Activity: Insights from Molecular Docking and Molecular Dynamics Simulation.

In response to the urgent demand for innovative antibiotics, theoretical investigations have been employed to design novel analogs. Because griseofulvin is a potential antibacterial agent, we have designed novel derivatives of griseofulvin to enhance its antibacterial efficacy and to evaluate their interactions with bacterial targets using in silico analysis. The results of this study reveal that the newly designed derivatives displayed the most robust binding affinities towards PBP2, tyrosine phosphatase, and FtsZ proteins.

In Silico Exploration of Microtubule Agent Griseofulvin and Its Derivatives Interactions with Different Human β-Tubulin Isotypes.

Tubulin isotypes are known to regulate microtubule stability and dynamics, as well as to play a role in the development of resistance to microtubule-targeted cancer drugs. Griseofulvin is known to disrupt cell microtubule dynamics and cause cell death in cancer cells through binding to tubulin protein at the taxol site. However, the detailed binding mode involved molecular interactions, and binding affinities with different human β-tubulin isotypes are not well understood.

Griseofulvin: An Updated Overview of Old and Current Knowledge.

Griseofulvin is an antifungal polyketide metabolite produced mainly by ascomycetes. Since it was commercially introduced in 1959, griseofulvin has been used in treating dermatophyte infections. This fungistatic has gained increasing interest for multifunctional applications in the last decades due to its potential to disrupt mitosis and cell division in human cancer cells and arrest hepatitis C virus replication.

In Silico Molecular Dynamics of Griseofulvin and Its Derivatives Revealed Potential Therapeutic Applications for COVID-19.

Treatment options for Coronavirus Disease 2019 (COVID-19) remain limited, and the option of repurposing approved drugs with promising medicinal properties is of increasing interest in therapeutic approaches to COVID-19. Using computational approaches, we examined griseofulvin and its derivatives against four key anti-SARS-CoV-2 targets: main protease, RdRp, spike protein receptor-binding domain (RBD), and human host angiotensin-converting enzyme 2 (ACE2). Molecular docking analysis revealed that griseofulvin (CID 441140) has the highest docking score (-6.

Conservation of griseofulvin genes in the gsf gene cluster among fungal genomes.

The polyketide griseofulvin is a natural antifungal compound and research in griseofulvin has been key in establishing our current understanding of polyketide biosynthesis. Nevertheless, the griseofulvin gsf biosynthetic gene cluster (BGC) remains poorly understood in most fungal species, including Penicillium griseofulvum where griseofulvin was first isolated. To elucidate essential genes involved in griseofulvin biosynthesis, we performed third-generation sequencing to obtain the genome of P.

Two carbapenem-resistant ST1:ST231:KL1:OCL1 strains recovered in Tehran, Iran, carry AbaR31 in the chromosome and AbaR4 and Tn in a RepAci6 plasmid.

Objectives: To analyse the context of genes conferring antibiotic resistance in two carbapenem-resistant isolates recovered in Tehran, Iran.

Methods: The antibiotic resistance phenotype for 28 antibiotics was determined using disc diffusion. The whole genome sequences of ABH008 and ABS200 were determined using the Illumina HiSeq X Ten platform.

Predicting mammalian species at risk of being infected by SARS-CoV-2 from an ACE2 perspective.

SARS-CoV-2 can transmit efficiently in humans, but it is less clear which other mammals are at risk of being infected. SARS-CoV-2 encodes a Spike (S) protein that binds to human ACE2 receptor to mediate cell entry. A species with a human-like ACE2 receptor could therefore be at risk of being infected by SARS-CoV-2.

Coronavirus genomes carry the signatures of their habitats.

Coronaviruses such as SARS-CoV-2 regularly infect host tissues that express antiviral proteins (AVPs) in abundance. Understanding how they evolve to adapt or evade host immune responses is important in the effort to control the spread of infection. Two AVPs that may shape viral genomes are the zinc finger antiviral protein (ZAP) and the apolipoprotein B mRNA editing enzyme-catalytic polypeptide-like 3 (APOBEC3).

Molecular mechanisms and prevalence of colistin resistance of Klebsiella pneumoniae in the Middle East region: A review over the last 5 years.

The increasing prevalence of multidrug-resistant (MDR) Klebsiella pneumoniae is a serious clinical and public health problem, and colistin is the last-resort treatment option for MDR infections. However, resistance to colistin has been increasingly reported in the world, such as the Middle East region, where antibiotics are used more in the human and agriculture industry. In this paper, we review the available data on the molecular mechanisms and prevalence of colistin resistance of K.

Accumulation of Antibiotic Resistance Genes in Carbapenem-Resistant Isolates Belonging to Lineage 2, Global Clone 1, from Outbreaks in 2012-2013 at a Tehran Burns Hospital.

The worldwide distribution of carbapenem-resistant (CRAB) has become a global concern, particularly in countries where antibiotic prescription is not tightly regulated. However, knowledge of the genomic aspects of CRAB from many parts of the world is still limited. Here, 50 carbapenem-resistant isolates recovered at a single hospital in Tehran, Iran, during several outbreaks in 2012 and 2013 were found to be resistant to multiple antibiotics.

Amikacin resistance due to the aphA6 gene in multi-antibiotic resistant Acinetobacter baumannii isolates belonging to global clone 1 from Iran.

Background: TnaphA6-carrying repAci6 plasmids have been detected in Acinetobacter baumannii isolates belonging to global clones, GC1 and GC2, worldwide. Here, we examined whether RepAci6 plasmids family play a role in the dissemination of the aphA6 in GC1 A. baumannii isolates from Iran.

The Activity of Fosfomycin Against Extended-Spectrum Beta-Lactamase-Producing Isolates of Enterobacteriaceae Recovered from Urinary Tract Infections: A Single-Center Study Over a Period of 12 Years.

Despite global efforts to tackle resistance in extended-spectrum beta-lactamase (ESBL)-producing isolates via old antibiotics, there are limited data on the efficacy of fosfomycin-an old oral antibiotic-against Enterobacteriaceae in the Middle East. The purpose of this study was to evaluate the in vitro activity of fosfomycin against urinary ESBL-producing isolates of Enterobacteriaceae. Between 2004 and 2015, 363 isolates of ESBL-producing Enterobacteriaceae were recovered from high-risk patients suffering from cardiac disorders and were subjected to polymerase chain reaction using specific primers for the bla, bla, and bla genes.