Anti-Infective Agents - Volume 19, Issue 4, 2021

Currently, mankind is fighting against an invisible enemy. The novel Coronavirus disease (COVID-19) has been spreading at a rapid rate across the world, which made the World Health Organization (WHO) to declare it as pandemic disease. COVID-19 is an acute respiratory tract infection that was first reported in December 2019, initially presented as pneumonia of unknown etiology in a group of patients in Wuhan, a city in the Hubei Province of China. Sometimes, animals infected with coronavirus infect humans and spread further via human-to-human transmission similar to the case of Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome-related coronavirus (SARS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), previously referred to as 2019-nCoV (COVID-19). SARS-- CoV-2 is an extremely pathogenic virus and is crushing the well-equipped health systems of developed countries. According to the WHO situation report updated on October 25, 2020 over 42 million cases and 1.1 million deaths have been reported globally. Since the figure of cases continues to increase, these viruses create a threat to global public health. This review summarizes an overview of the study of the novel coronavirus, including origin, epidemiology, etiology, targets for viral entry, and describes the clinical manifestation, diagnosis, and therapeutics used in clinical settings. Furthermore, our review focuses on the most up-to-date clinical information for the effective management, prevention, and counseling to control COVID-19 worldwide.

With the current scenario of emerging drug-resistant microbial strains, there prevails a continuous threat to health and the development of new antimicrobial agents is a challenging task. Quantitative Structure Activity Relationship (QSAR) has proven to elevate the likelihood of finding a new pharmacophore. Intermolecular binding like hydrophobic bond, electrostatic and steric interactions helps to understand drug interaction with the receptors. Some common conclusions have been drawn after analyzing diverse case studies. Few descriptors were identified to be common in enhancing the antimicrobial activity. The structural features modifying the antimicrobial activity were analyzed using critically published results from significant QSAR studies on antimicrobial compounds. This commentary will assist the synthetic chemist in synthesizing novel derivatives, which could be potential antimicrobial compounds.

Introduction: Today, we see advances in the use of medicinal plants in the treatment of fungal infections. Curcumin has major antimicrobial, antifungal, antimutagenic, and anticancer activities. This systematic review study is designed to evaluate the effectiveness of curcumin on a dermatophyte fungus, Trichophyton spp. Methods: In this study, antifungal effects of curcumin on the different strains of Trichophyton were evaluated. For this reason, several databases, including PubMed, Scopus, Web of Science, Embase and Google Scholar were searched systematically in years from1995 to 2020. Only articles with at least English abstracts were evaluated. The syntax was constructed with the combination of some keywords along with specific tags used for each of the databases. Results: In this systematic review, studies showed that curcumin has a potent effect on the inhibition of Trichophyton growth. Of the 2,500 studies in the search step, only 11articleswere eligible for the survey, 6 of which were on T.rubrum, 3 on T. mentagrophytes, 1 on both T. mentagrophyte and T. rubrum, and 1 on T. longifusus. Conclusion: Today, due to an increase in drug resistance to antifungal agents, plant extracts can be a good alternative in controlling fungal diseases. Curcumin and its compounds are effective in inhibiting or reducing Trichophyton infections in vitro and in vivo.

Background: Entamoeba histolytica is a causative agent of amoebiasis, estimated to cause more than 100,000 deaths per year. Metronidazole is used to treatment of E. histolytica infection. However, this drug has several untoward side effects, the current study was designed to analysis of the bioactive chemical products in extracts of Reseda sphenocleoides leaves and evaluation of anti-amoebic activity in vitro. Methods: Bioactive chemical compounds were tested by GC-MS and FT-IR. Entamoeba histolytica was cultured under xenic conditions in Locke's egg (LE) medium and different concentrations of extracts of R. sphenocleoides were added to cultivated parasites. Results: 11 and 18 bioactive phytochemical compounds were shown in the ethanolic and aqueous extracts of R. sphenocleoides leaves, respectively, by GC-MS analysis. FT-IR analysis of extracts of R. sphenocleoides leaves proved the presence of many functional groups for various phytocompounds. The ethanolic extract of R. sphenocleoides leaves was inhibited the growth of E. histolytica in vitro at concentrations 5 and 10 mg/ml after 96 hrs of incubation. At the same time, the highest concentration 20 mg/ml used in this study, inhibited the E. histolytica at all times of incubation. The aqueous extract showed that there was no growth of E. histolytica at the concentrations of 5 and 10 mg/ml after 72 and 48 hrs, respectively. However, the higher concentrations (15 and 20 mg/ml) of the aqueous extract were on the growth of E. histolytica parasite during the period of incubation. It was found that the minimum inhibitory concentration (MIC) for ethanolic and aqueous extracts of R. sphenocleoides leaves was <15 mg/ml and <10 mg/ml, respectively. Conclusion: The results specify that the extracts of R. sphenocleoides has a higher capacity of reducing E. histolytica number in vitro. Moreover, these results showed that the extracts of R. sphenocleoides contain various bioactive compounds and therefore have various medicinal properties that can be used for the treatment of various diseases.

Background: Identification of non-tuberculosis mycobacteria by culture and phenotypic description is commonly used; however, it takes 4 to 6 weeks or even a longer time for slow growing species as well as for identification of some species that may be missed by biochemical characteristics methods. This study aimed to evaluate Real Time PCR for Detection of NTM by Amplification of Internal Transcribed Spacer (ITS) and 16S rRNA. Methods: In our investigation, using Real Time PCR and two pairs of unique primers targeted to ITS and 16S rRNA genes as well as Beta-actin as an internal control, Non tuberculosis mycobacteria species were detected. Results: Real time PCR was performed on the prepared dilutions. In addition, the threshold of sensitivity in this study was 10pg. To test the specificity, the genome of several bacteria responsible for respiratory infections was used, in which only the test response related to the non-tuberculosis mycobacterium genome and internal control was positive. Conclusion: In this research, an effective and up-to-date Real Time PCR method was used to design a diagnostic kit from all aspects. To avoid any error or mistake and to minimize the false results, internal control was used. The ability to design diagnostic kits allows us to increase efficiency, minimize mistakes, and save a considerable amount of time and cost.

Background: Sidr honey has been reported to exhibit antimicrobial activity against numerous pathogenic bacteria making this honey a promising functional food for the treatment of wounds or stomach ulcers. Objective: The purpose of this study was to investigate the effect of Sidr honey against P. aeruginosa and S. pyogenes. Methods: Minimum inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) for Sidr honey were determined by the broth dilution method. The growth curve of both bacteria with MIC, half-MIC, and quarter-MIC was monitored by optical density (at OD570). The timekill curve was used to determine the bacteriostatic and bactericidal activity of Sidr honey on both bacteria by plotting colony-forming unit (CFUs) versus time. The effect of Sidr honey on the ultrastructure of the P. aeruginosa and S. pyogenes was investigated using scanning electron microscopy (SEM). The effect of Sidr honey on the expression of virulence genes in both bacteria was determined using quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Results: The results showed that Sidr honey possessed the lowest MIC value against P. aeruginosa and S. pyogenes with 12.5% (w/v) and 20% (w/v), respectively. In addition, the MBC value for Sidr honey was found to be 20% (w/v) and 25% (w/v) against P. aeruginosa and S. pyogenes respectively. Growth curves conducted with MIC Sidr honey resulted in no growth of P. aeruginosa and S. pyogenes. Growth curves with half-MIC Sidr honey resulted in a reduced growth rate and reduction in overall cell number in both bacteria over a period of 24 h, compared with cells grown without honey. In the time-kill curve, treatment of P. aeruginosa and S. pyogenes with Sidr honey for 8 hours resulted in decreases of 4-log reduction (P < 0.05) in total viable counts (TVCs). SEM analysis revealed marked changes in the bacterial cell morphology for both bacteria following treatment with Sidr honey. These changes included the appearance of irregular shapes, incomplete cell division, and swelling cells. The RT-qPCR results showed that the expression of algD, oprF, fleN, fleQ, fleR, fliA, and fliC in P. aeruginosa decreased 0.43-fold, 0.38-fold, 0.41-fold, 0.51-fold, 0.40-fold, 0.61-fold, and 0.39-fold respectively after exposure to Sidr honey. Meanwhile, the expression of sof, sfbl, and scpA in S. pyogenes decreased 0.18-fold, 0.21-fold, and 0.28-fold respectively, after treated with Sidr honey. Conclusion: Using varying methods to evaluate the planktonic integrity, this study demonstrated that Sidr honey has antibacterial activity against both bacteria and has potential as a therapeutic agent for microbial infection, particularly against these two organisms. To our knowledge, this study is the first to indicate that Sidr honey is effective at inducing cell lysis and identify target genes at the genetic level that might be involved in this process.

Introduction: The housefly (Musca domestica) is an important host for various pathogenic bacteria, including the ESKAPE group, and acts as a reservoir for transmitting resistance factors. In this regard, this study was performed in order to survey the role of houseflies as a mechanical vector for ESKAPE pathogens and antibiotic resistance profiles of these strains in the four teaching hospitals and rural areas in Babol, north of Iran. In this cross-sectional study, 280 adult house flies were collected with a sterilized nylon net. Methods: All samples were put inside separately in a sterile tube and anesthetized using freezing at 0#146;C for 5 minutes. Bacterial isolates were identified from the external and internal surfaces. The antibiotic susceptibility test was performed by the disk diffusion method. A. baumannii, P. aeruginosa, and Enterobacter isolates were not detected in rural samples. Only one methicillin-resistance S. aureus was found in rural flies. In hospitals, the prevalence of the ESKAPE pathogens in the Cuticular surface and GI were 22.9% and 22.1%, respectively. Results: In total, the highest and lowest frequency rate was related to P. aeruginosa (6.1%) and A. baumannii (1.1%). Also, 66.7%, 5.9%, and 12.5% of A. baumannii, P. aeruginosa, and Enterobacter were resistant to imipenem, respectively. 21.4% of E. faecium were resistant to vancomycin. In total, 63 (22.5%) bacterial species collected from both the cuticular surface and GI, 29 (46%) were multidrug- resistant (MDR). Conclusion: Houseflies obtained from hospitals may be involved in the distribution of drug-resistant bacteria and may increase the potential of human exposure to drug-resistant organisms.

Background: Enterobacteriaceae, the normal dwellers in the human intestine, are commonly associated with a variety of community-acquired and nosocomial infections. An emerging trend of antibiotic resistance among these strains is a notable issue globally; a more serious threat is the resistance against the available last resort antibiotics- the carbapenems. Objective: The objective of our study was intended to determine the burden of resistance towards common antibiotic classes so as to address the gap of drug resistance prevalence data, among the Enterobacteriaceae isolates obtained from the health settings in this region. Methodology: A cross-sectional study was done with an inclusion of clinical isolates collected from varied sources from health settings in upper Assam. The isolates were identified based on standard methods of morphology study and biochemical tests. The identified isolates were then subjected to antibiotic susceptibility testing by following the Kirby-Bauer disc diffusion method, and the result was interpreted as per the CLSI guidelines. The resistance of the reported carbapenem-resistant isolates was confirmed by minimum inhibitory concentration (MIC) determination using a commercial E-strip kit. Results: Among the enterobacterial isolates Klebsiella spp. accounted for the majority, followed by Escherichia coli, Citrobacter spp., Shigella spp. and others. Multi-drug resistance (MDR) was noted among 67.6% isolates; however, carbapenem resistance was confirmed in 18.9% of the total Enterobacteriaceae isolates. Conclusion: Higher prevalence of resistance towards carbapenems, among the Enterbacteriaceae isolates of upper Assam seems to be an upcoming threat to the region, limiting the treatment options in the future.

Objective: Recent pandemic caused by the SARS-CoV-2, first described in Wuhan city of China in December 2019, spread widely in almost all the countries of the world. Coronavirus (COVID-19) led to the unexpected death of many people and caused a severe economic loss in a number of countries. Virtual screening based on molecular docking, drug-likeness prediction, and in silico ADMET studies are some of the effective tools for the identification of small molecules as novel antiviral drugs to treat diseases. Methods: In the current study, virtual screening was performed through molecular docking for identifying potent inhibitors against Mpro enzyme from the ZINC library for the possible treatment of the COVID-19 pandemic. Interestingly, some compounds have been identified as possible anti-covid-19 agents for future research. A total of 350 compounds were screened based on their similarity score with reference compound X77 from ZINC data bank and were subjected to docking with crystal structure available of Mpro enzyme. These compounds were then filtered by their in silico ADME-Tox and drug-likeness prediction values. Results: Out of these 350 screened compounds, 10 compounds were selected based on their docking score and best-docked pose in comparison to the reference compound X77. In silico ADME-Tox and drug likeliness predictions of the top compounds were performed and showed excellent results. All the 10 screened compounds showed a significant binding pose with the target main protease (Mpro) enzyme and satisfactory pharmacokinetic and toxicological properties. Conclusion: Based on these results, it is suggested that the identified compounds may be considered for therapeutic development against the COVID-19 virus and can further be evaluated for in vitro activity, preclinical, clinical studies, and formulated in a suitable dosage form to maximize their bioavailability.