Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) - Volume 23, Issue 5, 2023

In the German towns of Marburg, Frankfurt, and Belgrade in 1967, this single negativestranded RNA virus was initially discovered. The importation of infected grivet monkeys from Uganda is what caused this virus-related sickness. As a result of the early link between viruses and non-human primates, this virus is frequently referred to as vervet monkey sickness. This virus causes Marburg hemorrhagic fever in humans and non-human primates. Human endothelial cells serve as the primary vehicle for replication. According to a 2009 report, the virus was being stored in Egyptian fruit bats (Rousettus aegyptiacus). Body fluids, unprotected sex, broken or injured skin, and other bodily fluids are the main routes of transmission. After the incubation period, symptoms like chills, headaches, myalgia, and stomach pain start to show up. There is no specific medication for such an infection, only hydration therapy and adequate oxygenation are followed. The following diagnostic techniques can be used to confirm the diagnosis: (i) an antibody-capture enzyme linked immunosorbent assay (ELISA); ii) an antigen capture ELISA test; iii) a serum neutralization test; iv) an RT PCR assay; v) electron microscopy; or vi) virus isolation by cell culture. Because MARV is a risk group 4 infection, laboratory staff must take strict precautions (RG-4).

The current world is plagued by unpredictability as a result of various COVID-19 variants. The current variants of concern (VOCs) are B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma) and B.1.617/B.1.617.2(Delta). WHO classified two variants, delta (B.1.617.2) and omicron (B.1.1.529), as having highly mutable strikes. The WHO predicted that it would be more dangerous than previous variants due to its mutatable capability. The Omicron variant of coronavirus has caused widespread disruption, with countries struggling to manage the massive number of infections. Due to its unique properties, such as protein structure, symptoms, transmission, and epidemiology, this review aims to compare omicron to other variants. Furthermore, we have highlighted vaccines that have been used to combat this pandemic.

Background: Tuberculosis is the second leading cause of death from infectious diseases worldwide. Multidrug-resistant Mycobacterium tuberculosis is spreading throughout the world, creating a crisis. Hence, there is a need to develop anti-tuberculosis drugs with novel structures and versatile mechanisms of action. Objective: In this study, we identified antimicrobial compounds with a novel skeleton that inhibits mycobacterium decaprenylphosphoryl-β-D-ribose oxidase (DprE1). Methods: A multi-step, in silico, structure-based drug screening identified potential DprE1 inhibitors from a library of 154,118 compounds. We experimentally verified the growth inhibitory effects of the eight selected candidate compounds against Mycobacterium smegmatis. Molecular dynamics simulations were performed to understand the mechanism of molecular interactions between DprE1 and ompound 4. Results: Eight compounds were selected through in silico screening. Compound 4 showed strong growth inhibition against M. smegmatis. Molecular dynamics simulation (50 ns) predicted direct and stable binding of Compound 4 to the active site of DprE1. Conclusion: The structural analysis of the novel scaffold in Compound 4 can pave way for antituberculosis drug development and discovery.

Background: Pseudomonas (P.) aeruginosa is one of the leading causes of nosocomial infections. The pathogenicity of P. aeruginosa is related to its inherent antimicrobial resistance and the diverse virulence factors of this bacterium. Owing to the specific role of exotoxin A in P. aeruginosa pathogenesis, it is known as a promising therapeutic candidate to develop antibodies as an alternative to antibiotics. Objective: The present study aimed to validate the interaction between a single-chain fragment variable (scFv) antibody identified from an scFv phage library against domain I exotoxin A by bioinformatic tools. Methods: For this, several bioinformatics tools, including Ligplot, Swiss PDB viewer (SPDBV), PyMOL, I-TASSER, Gromacs, and ClusPro servers were used to evaluate the interaction of scFv antibody with P. aeruginosa exotoxin A. The I-TASSER server was utilized to predict the function and structure of proteins. The interaction of two proteins was analyzed using ClusPro tools. The best docking results were further analyzed with Ligplot, Swiss PDB viewer, and PyMOL. Consequently, molecular dynamics simulation was utilized to predict the stability of the secondary structure of the antibody and the binding energy of the scFv antibody to the domain I of exotoxin A. Results: As a result, we demonstrated that data from computational biology could provide proteinprotein interaction information between scFv antibody/domain I exotoxin A and offers new insights into antibody development and therapeutic expansion. Conclusion: In summary, a recombinant human scFv capable of neutralizing P. aeruginosa exotoxin A is recommended as a promising treatment for infections caused by P. aeruginosa.

Background: With an increasing trend of pathogenic bacteria developing resistance to the existing drugs, there is a need for newer therapeutic measures. Nigella sativa seeds and oil have been used for decades as Ayurveda, Unani Tibb and other forms of traditional medicine for various disorders. Thymoquinone is one of the active components of the N. sativa seeds. Objective: The present study determines the antibacterial effect of crude methanolic extract N. sativa seeds and thymoquinone against bacteria causing wound infection. Methods: Samples obtained from cases of wound infection received at a Microbiology laboratory attached to a tertiary care hospital over a period of six months were included in the study. The antibacterial effect of crude methanolic extract of N. sativa seeds was determined by the Punch Well method. The minimum inhibitory concentration (MIC) of thymoquinone against bacteria isolated from cases of wound infection was determined by the Micro Broth Dilution technique. Results: A total of 60 isolates were collected from 60 samples of wound infection. By the Punch Well method, Staphylococcus aureus showed varying zones of inhibition whereas all gram-negative bacilli and Enterococcus faecalis did not show any zone of inhibition. Thymoquinone showed good antibacterial activity against S. aureus with MIC values ranging from 2-8μg/ml for most of the isolates. Uniformly, MIC of thymoquinone against all gram-negative bacilli and E. faecalis was >128μg/ml, p<0.001. It was found that methicillin-resistant S. aureus (MRSA) isolates showed higher MIC than methicillin sensitive S. aureus (MSSA) isolates p<0.05. Conclusion: Antibacterial activity of thymoquinone was very good against S. aureus but showed limited activity against Enterobacteriaceae members and E. faecalis isolated from patients with wound infection. Thymoquinone may be considered a potential antibacterial agent against wound infection caused by S. aureus.

Cryptosporidiosis is caused by infection with a coccidian parasite belonging to the genus Cryptosporidium. Initially, human cryptosporidiosis was believed to be caused only by one species, but since the advent of molecular studies, 15 more species have been discovered to cause this infection. Among them, Cryptosporidium hominis and Cryptosporidium parvum are the most common species involved. This mainly affects children and causes diarrhea in most cases. It is mainly diagnosed by microscopy, especially in low-middle-income countries. This review covers the epidemiology, life cycle, risk factors, clinical manifestations, different diagnostic methods and treatment of this disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induced coronavirus disease 2019 (COVID-19) pandemic has produced an unparalleled setback for the world's economy and health. One of the best therapies to significantly lower severe illness and mortality from SARS-CoV-2 infection is vaccination. Worldwide vaccination campaigns are being implemented. New-onset autoimmune problems, such as immune thrombotic thrombocytopenia, autoimmune liver disorders, IgA nephropathy, Guillain-Barré syndrome, systemic lupus erythematosus, and rheumatoid arthritis, have recently been described more frequently after receiving COVID-19 vaccine. The creation of specific autoantibodies, molecular mimicry, and the function of specific vaccine adjuvants all emerge to play a significant role in autoimmunity. The post-acute sequelae of SARS-CoV-2, usually known as Long Covid Syndrome, are beginning to be better understood in terms of the disparities in immune responses seen in individuals with and without the condition. We anticipate that the knowledge gleaned from several COVID-19 investigations will be put to use in research on the inflammatory mechanisms implicated in serious and protracted illnesses, which is still a key unmet need.

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) and patients with COVID-19 may be treated primarily with SARS CoV- 2-targeting drugs and the therapeutic agents assisting in the management of COVID-19 complications. This review focuses on the supplements like vitamins, minerals, herbal constituents, and others that help prevent or manage negative outcomes among COVID-19 patients. The literature was searched in databases such as Medline/PubMed Central/PubMed, Google Scholar, Science Direct, EBSCO, Scopus, EMBASE, the Directory of Open Access Journals (DOAJ), and reference lists to identify relevant articles. The vitamins, including vitamin C, and vitamin D, minerals such as zinc, selenium, and copper, herbal constituents like thymoquinone, curcumin, naringenin, quercetin, and glycyrrhizin, and other supplements, including N-acetylcysteine and melatonin. Melatonin have been identified as having the potential to manage patients with COVID-19 along with standard care. Some of the ongoing clinical trials are investigating the effectiveness of different supplements among COVID-19 patients.

Background: Adenovirus generally causes upper and lower respiratory tract infections. It is common in children and occasionally in adults. Neurological involvement is rare, which may be mild aseptic meningitis to potentially fatal acute necrotizing encephalopathy. Recently, viruses have been reported increasingly to cause CNS infections. Viral aetiology typically varies with age. Case Presentation: Here, we report an unusual adenovirus meningoencephalitis with a co-infection of neurocysticercosis in an immunocompetent adult patient. An 18-year-old healthy female student was admitted with fever and headache for 11 days and progressive altered behaviour for 5 days, followed by altered sensorium for 3 days. This variable and unusual presentation of adenoviral infection involving CNS provoked diagnostic difficulties, but with the help of advanced diagnostics, especially molecular, exact aetiology was detected. Even with the neurocysticercosis infection in this patient, the outcome was not adversely affected. Conclusion: This unusual co-infection with a successful outcome is the first case of this type in literature.

Introduction: SARS-CoV-2 cause pneumonia can spread across the lung and lead to acute respiratory distress syndrome (ARDS) in severe cases. Post-exposure prophylaxis has shown great potential to prevent the transmission of some viral infections; however, such results for COVID-19 are still inconclusive. Methods: Therefore, the aim of this study was to systematically review the resources that utilized postexposure prophylaxis (PEP) for COVID-19 and the possible clinical benefits of such drugs. An organized search of relevant literature was done using the keywords and search queries on public databases of Cochrane, PubMed, Web of Science and Scopus from December 2019 to August 23, 2021. Original resources that had the inclusion criteria were included after two-phase title/abstract and full-text screenings. This review adhered to the Preferred Reporting Items for Systematic Reviews and Meta- Analysis (PRISMA) statement. Results: Out of 841 retrieved records 17 resources were appropriate to include in the systematic review. Hydroxychloroquine with a daily dose of 400-800 mg and a duration of 5-14 days was the most frequently used agent for PEP. Chloroquine was recommended to use to control treatment in patients with mild to severe COVID-19 pneumonia. Other agents like Lopinavir-ritonavir (LPV/r), angiotensinconverting enzyme inhibitors (ACEIs), Angiotensin receptor blockers (ARBs), Vitamin D, arbidol, thymosin drugs, and Xin guan no.1 (XG.1, a Chinese formula medicine) have also been applied in some studies. Conclusion: Current evidence demonstrated no established clinical benefits of any drug as PEP in individuals with COVID-19. However, scarce indication occurs for the beneficial effects of some agents, but more studies are needed to explore such effects.