Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) - Volume 24, Issue 8, 2024

Every year witnesses an outbreak of some or the other zoonotic disease that causes the unparalled loss of human life. The year 2022 presented the outbreak of Crimean Congo haemorrhagic fever (CCHF), which brought unprecedented challenges to individuals as well as to the healthcare system all around the world, making it a serious health concern. Rising health concerns have highlighted the importance of managing and decreasing the further transmission of the CCHF virus. CCHF is one of tick-borne viral diseases, which spreads due to various reasons like changes in global warming, environmental influences, and other ecological factors. All these factors somehow impact the disease prevalence. This disease has a negative impact on both humans and livestock. The diverse climate and significant livestock population of India make it susceptible to the prevalence of CCHF. Therefore, it is the need of the hour to develop some strategies in order to tackle the challenges posed by CCHF. This article includes all the cases of CCHF that have occurred in India from the year 2011, along with the fatality rates associated with this disease. Also this study discusses the need to explore some specific drugs for the management and prevention of such diseases. In addition, the pathogenesis of the disease progression, along with some protective measures suggested by the government has been described for prevention of CCHF. Subsequently, this article attempted to draw attention towards the risk that may be posed by CCHF in the coming scenario, emphasizing the importance of taking proactive measures in anticipation of such risks.

Background: Regarding scientific research, Imidazo[1,2-a] pyridine derivatives are constantly being developed due to the scaffold’s intriguing chemical structure and varied biological activity. They are distinctive organic nitrogen-bridged heterocyclic compounds that have several uses in medicines, organometallics and natural products. It has become a vital tool for medicinal chemists. Methods: In order to gather scientific information on Imidazo[1,2-a] pyridines derivative, Google, PubMed, Scopus, Google Scholar, and other databases were searched. In the current study, the medicinal value and therapeutic effect of Imidazo[1,2-a] pyridines were investigated using above mentioned databases. The current study analyzed the detailed pharmacological activities of Imidazo[1,2-a] pyridine analogs through literature from diverse scientific research works. Results: Due to its wide range of biological activities, including antiulcer, anticonvulsant, antiprotozoal, anthelmintic, antiepileptic, antifungal, antibacterial, analgesic, antiviral, anticancer, anti-inflammatory, antituberculosis, and antitumor properties, imidazopyridine is one of the most significant structural skeletons in the field of natural and pharmaceutical products. An imidazopyridine scaffold serves as the basis for a number of therapeutically utilized medications, including zolpidem, alpidem, olprinone, zolimidine, and necopidem. Conclusion: This comprehensive study covers the period of the last five years, and it sheds light on the developments and emerging pharmacological actions of Imidazo[1,2-a] pyridines. Additionally, the structure-activity relationship and molecular docking studies are carefully documented throughout the paper, providing medicinal chemists with a clear picture for developing new drugs.

Background: Severe COVID-19 or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a kind of viral pneumonia induced by infection with the coronavirus that causes ARDS. It involves symptoms that are a combination of viral pneumonia and ARDS. Antiviral or immunosuppressive medicines are used to treat many COVID-19 patients. Several drugs are now undergoing clinical studies in order to see if they can be repurposed in the future. Material and Methods: In this study, in silico biomarker-targeted methodologies, such as target/ molecule virtual screening by docking technique and drug repositioning strategy, as well as data mining approach and meta-analysis of investigational data, were used. Results: In silico findings of used combination of drug repurposing and high-throughput docking methods presented acetaminophen, ursodiol, and β-carotene as a three-drug therapy regimen to treat ARDS induced by viral pneumonia in addition to inducing direct antiviral effects against COVID-19 viral infection. Conclusion: In the current study, drug repurposing and high throughput docking methods have been employed to develop combination drug regimens as multiple-molecule drugs for the therapy of COVID-19 and ARDS based on a multiple-target therapy strategy. This approach offers a promising avenue for the treatment of COVID-19 and ARDS, and highlights the potential benefits of drug repurposing in the fight against the current pandemic.

Background: The toxin-antitoxin system is a genetic element that is highly present in Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis. The toxin-antitoxin system comprises toxin protein and antitoxin protein or non-encoded RNA interacting with each other and inhibiting toxin activity. M. Tuberculosis has more classes of TA loci than non-tubercle bacilli and other microbes, including VapBC, HigBA, MazEF, ParDE, RelBE, MbcTA, PemIK, DarTG, MenTA, one tripartite type II TAC chaperone system, and hypothetical proteins. Aims: The study aims to demonstrate the genes encoded toxin-antitoxin system in mycobacterium tuberculosis strains from clinical samples. Materials and Methods: The pulmonary and extra-pulmonary tuberculosis clinical samples were collected, and smear microscopy (Ziehl-Neelsen staining) was performed for the detection of high bacilli (3+) count, followed by nucleic acid amplification assay. Bacterial culture and growth assay, genomic DNA extraction, and polymerase chain reaction were also carried out. Results: The positive PTB and EPTB samples were determined by 3+ in microscopy smear and the total count of tubercle bacilli determined by NAAT assay was 8.0×100⁵in sputum and 1.3×10⁰⁴CFU/ml in tissue abscess. Moreover, the genomic DNA was extracted from culture, and the amplification of Rv1044 and Rv1045 genes in 624 and 412 base pairs (between 600-700 and 400-500 in ladder), respectively, in the H37Rv and clinical samples was observed. Conclusion: It has been found that Rv1044 and Rv1045 are hypothetical proteins with 624 and 882 base pairs belonging to the AbiEi/AbiEii family of toxin-antitoxin loci. Moreover, the significant identification of TA-encoded loci genes may allow for the investigation of multidrugresistant and extensively drug-resistant tuberculosis.

Background: Malaria is still the deadliest parasitic disease caused by Plasmodium spp. Due to drug resistance and their unpleasant side effects, of conventional researchers are enormously seeking to achieve antimalarial drugs with more curative effective, less toxic and cost-affordable drugs using more advanced technology such as nanodrugs. Purpose: The present study aimed to examine the antimalarial effects of a novel synthesized nonochloroquine-loaded curcumin relying on dendrimer G2 in susceptible mice. Methods: Antimalarial activity and toxicity of the nanocomposite were examined on BALB/C mice with microscopy, checking RBCs morphology and related enzymatic activity rate. Results: The maximum inhibitory effect of the nanocomposite was seen at 10 mg/kg, killing 98% of P. berghei compared to sole chloroquine, whereas ED50 was reported at 5.5 mg/kg. The safety of the synthesized nanocomposite was confirmed with biochemical tests with no detrimental effects on mice. The sustainability and longevity of the nanodrug increased significantly with the NDC-CQ assay compared to the control groups. Conclusion: The study showed that nonochloroquine-loaded curcumin had a promising inhibitory effect on P. berghei growth in infected mice compared to standard drugs. However, further studies and clinical trials with large samples are recommended to study different aspects of using nanodrug.

Background: Sepsis is a major health problem worldwide and is associated with high morbidity and mortality with every hour delay in initiation of therapy. A conventional method of blood culture and Antimicrobial Susceptibility Testing (AST) takes around 48-72 hours. Empirical antibiotics need to be administered until the sensitivity report is made available. It has been estimated that 20-50% of the empirical antibiotics are inappropriate, resulting in prolonged hospital stays, adverse effects, and emergence of drug resistance. Additionally, this also puts an extra financial burden on both the patients and healthcare settings. Performing direct Antimicrobial Sensitivity Testing (dAST) is an important tool to reduce turn-around time (TAT) by at least 18-24 hours, thus reducing morbidity and mortality among critically ill patients. Methods: Direct AST (dAST) was performed from the positively flagged blood culture bottles received between December, 2021 to May, 2022 from Intensive Care Units (ICUs) on Mueller- Hinton Agar (MHA) using four drops of withdrawn blood. dAST was performed for six drugs: Ceftriaxone-30 μg (CTR), Piperacillin/Tazobactam-100/10 μg (PIT), Meropenem-10 μg (MRP), Ciprofloxacin-5 μg (CIP), Aztreonam-30 μg (AT), and Colistin (CL). The zone of inhibition was interpreted as per CLSI M100 ed32, 2022 guidelines. A parallel conventional method was also performed to examine for categorical agreement and disagreement. Identification was carried out using MALDI-TOF MS from the colonies that appeared on the dAST plate on the subsequent day. Results: A total of 162 positively flagged blood culture bottles were included in the study. The majority of the Gram-negative organisms were from Enterobacterales (n=109), followed by Acinetobacter spp. (n=28) and Pseudomonas aeruginosa (n=25). Out of the 972 isolate-antimicrobial combinations, overall Categorical Agreement (CA) was seen in 936 (96.3%), whereas disagreement was observed in 36 with minor error (mE) in 21 (2.2%), major error (ME) in 7 (0.7%), and very major error (VME) in 8 (0.8%) when compared to the routine method. Categorical agreement (CA) of > 99% was seen in ceftriaxone (CTR) and ciprofloxacin (CIP). In comparison, the lowest CA was observed with meropenem (MRP) at 92%. Colistin dAST was performed using the E-strip method, and the result obtained was highly convincing, with an overall disagreement of only 1.2%. Conclusion: Rapid dAST from positively flagged blood culture bottles proved to significantly reduce the TAT from the time of sample collection to the first availability of antimicrobial susceptibility report with excellent categorical agreement of > 95% using the conventional disc diffusion method. Results obtained were within the acceptance criteria set by U. S. Food and Drug Administration (FDA) guidelines of > 90% categorical agreement for a new method. We were able to obtain excellent concordance for colistin using the E-strip method. Performing dAST not only saves a “day”, but its proper implementation would save a “life”.