Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) - Volume 22, Issue 5, 2022

Background: In December 2019, a new coronavirus (nCoV) emerged as a public health concern spreading all around the world. Several attempts have been made to discover effective drugs and vaccines. Up to now, multiple COVID-19 vaccines have been developed against this mysterious virus, and a lot of individuals have already got vaccinated. Objective: Anti-viral drugs are effective in treating and managing COVID-19. Nucleoside reverse transcriptase inhibitors (NRTIs) are a collection of antiviral drugs for treating HIV and HBV infections. These drugs prevent virus replication by blocking reverse transcriptase (RT). In this review, we discuss the interaction of this class of anti- HIV drugs with specific functional proteins and enzymes of SARSCoV- 2. Methods: A search of the databases, including Web of Science, Embase, PubMed, Scopus, and Google Scholar, was conducted from commencement to September 2020. The relevant articles on the potential effects of NRTIs on COVID-19 were collected. Finally, twenty-three articles were selected, including all in vitro, in vivo, and clinical studies. Results: It was observed that RdRp, spike, ACE2, PNP, inflammatory cytokines, and nucleocapsid protein participate in the pathogenesis of SARS-CoV-2. NRTIs target these proteins by binding to them. Conclusion: This review is focused on the mechanisms of NRTIs to introduce them as potential therapies for COVID-19. However, further in vitro and in vivo investigations will provide helpful information for the identification of drug candidates as a part of COVID-19 management.

Coronavirus disease 2019 (COVID-19), which is a highly contagious viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a catastrophic effect on the world's demographics, resulting in more than 3.8 million deaths worldwide and establishing itself as the most serious global health crisis since the 1918 influenza pandemic. Several questions remain unanswered regarding the effects of COVID-19 disease during pregnancy. Although most infections are mild in high-risk populations, the severe disease frequently leads to intubation, intensive care unit admission, and, in some cases, death. Hormonal and physiological changes in the immune and respiratory systems, cardiovascular function, and coagulation may affect the progression of COVID-19 disease in pregnancy. However, the consequences of coronavirus infection on implantation, fetal growth and development, labor, and newborn health have yet to be determined, and, consequently, a coordinated global effort is needed in this respect. Principles of management concerning COVID-19 in pregnancy include early isolation, aggressive infection control procedures, oxygen therapy, avoidance of fluid overload, consideration of empiric antibiotics (secondary to bacterial infection risk), laboratory testing for the virus and co-infection, fetal and uterine contraction monitoring, prevention, and / or treatment of thromboembolism early mechanical ventilation for progressive respiratory failure, individualized delivery planning, and a team-based approach with multispecialty consultations. This review focuses on COVID-19 during pregnancy, its management, and the area where further investigations are needed to reduce the risk to mothers and their newborns.

Background: Flavonoid class phytochemicals are natural compounds present in different medicinal plants, vegetables and fruits. Ginkgo biloba contains significant amounts of bioflavonoid ‘bilobetin’. Bilobetin is an active phytochemical used for the treatment of human health complications due to its medicinal properties and therapeutic benefit. The purpose of this work is to collect and reviewed scientific data on bilobetin from different literature sources; highlight their biological properties, pharmacological activities and analytical aspects. Methods: Health beneficial aspects of bilobetin have been investigated in the present work through scientific data analysis. PubMed, Google Scholar, Google, Scopus, etc. have been searched in the present work in order to collect scientific information on bilobetin. Medicinal importance and therapeutic benefit of bilobetin has been searched in the present work through these databases of bilobetin. Detailed pharmacological activities of bilobetin have been reviewed in the present work through literature data analysis of various scientific research works. However, analytical data of bilobetin were also collected and reviewed in the present reaserch. Results: Literature data analysis of bilobetin in the present work revealed the medicinal properties and therapeutic potential of bilobetin mainly due to its anti-fungal, anti-inflammatory, anti-oxidant, antihyperlipidemic, and anti-proliferative activities. Literature data analysis revealed the effectiveness of bilobetin on osteoporosis, glucose metabolism, adipocytes, SARS CoV-2, Influenza A virus and human thrombin. Scientific data also revealed the importance of different analytical techniques for the isolation, separation, identification, and quantification of bilobetin. Conclusion: Scientific data analysis revealed biological importance and pharmacological activities of bilobetin in the health sector.

A cluster of unknown acute pneumonia cases by a novel coronavirus signaled an outbreak in Wuhan province of China in December 2019. The World Health Organization (WHO) initially declared COVID-19 as the global public health emergency on 30th January 2020 and subsequently a pandemic on March 11, 2020. It was also stated that the spread of COVID-19 may be interrupted by early detection, isolation, prompt treatment, and the implementation of a robust system to trace contacts. Testing is a key strategy and the role of Diagnostic Stewardship (DS) is essential to allocate and engage the present as well as new testing resources strategically, effectively, efficiently, and safely. Thus, diagnostic stewardship aims to select the right test for the right patient, at the right time to generate accurate, clinically relevant results which will optimally influence better clinical care outcomes and will conserve the available health care resources.

Lower Respiratory Tract Infections (LRTIs) and Upper Respiratory Tract Infections (URTIs) cause high morbidity and mortality worldwide. Lower respiratory tract infections are generally more serious than upper infections. Antibiotics are often inappropriately prescribed for patients with RTI. Inappropriate utilization of antibiotics, specifically the broad spectrum in respiratory tract infection, results in resistance to antibiotics. The common use of antibiotics is the prime reason for the spread of drug-resistant bacterial strains, which not only results in expensive treatments but also causes a high rate of morbidity and mortality due to undesired adverse effects of the drug. A literature survey was performed using PubMed, Science Direct, and Web of Science search engines. One hundred forty-five papers were retrieved, and more than 100 were included in this review. This article describes the overview and diagnosis of respiratory tract infections and the plethora of antibiotics that have been used in the management of RTIs.

Introduction: SARS-CoV-2 is the novel coronavirus that causes severe acute respiratory syndrome and could afflict individuals from all walks of life. Children are usually asymptomatic or represent non-specific mild to moderate symptoms; therefore, they often remain undiagnosed and could be potential reservoirs and silent carriers of the virus. Despite the global attention to COVID-19 and its importance in public health, some clinical and paraclinical aspects of this disease in children are still unclear. Thus, we conducted a comprehensive systematic review of available literature to reflect on the current knowledge and practice of the disease among children. Methods: This study was a systematic review of current evidence conducted in October 2020. We performed a systematic search using the keywords in online databases. The investigation adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist to ensure the reliability and validity of extracted literature and results. Results: We selected and reviewed 23 most related studies out of 1744 identified papers in an initial online search based on the inclusion and exclusion criteria of the present review; of whom 13 were original research studies, and 10 were letters to the editors, commentaries, viewpoints, consensus statements, and perspectives. Although due to the origin of the current pandemic, China was the country with the most publications (12 articles), data from several countries have been included in this review. Conclusion: COVID-19 can also affect children and cause systemic disease with several internal organ involvements. However, the prevalence, severity, and diversity of the symptoms in children are less than in adults. Cough and fever appear to be some of the most common symptoms, followed by other symptoms such as gastrointestinal manifestations. Comorbidities increase the risk of severe COVID-19 in children, and those without underlying conditions are very unlikely to suffer from severe disease. Mental health issues such as anxiety and depression due to the isolated situation caused by pandemics are common findings in children of early ages and should be seriously considered in current practice.

Background: Hepatitis C viral (HCV) infection is a major clinical burden globally. Pegylated IFN-α-2a (PEG-IFN-α-2a) with ribavirin (RIB) therapy induces an array of cellular antiviral responses, including dsRNA kinases (PKR), chemokines, and cytokines to tackle the HCV infection. However, many HCV patients develop resistance to PEG-IFN/RIB therapy rendering the therapy ineffective. Objectives: Here, we assess the significance of chemokines in response to PEG-IFN-α-2a with ribavirin (PEG-IFN/RIB) therapy. Methods: Twenty patients with HCV infection and ten healthy controls were enrolled in this study and patients were categorized into two groups 1), HCV-Responder (HCV-R), and 2) HCV-non-responder (HCV-NR). We analyzed IP-10, MIG, MCP-1, EOTAXIN, RANTES, IL-8, MIP-1a, and MIP-1b by a magnetic bead-based multiplex immunoassay approach based on Luminex X-MAP multiplex technology, using a MAGPIX instrument (Luminex Corporation, USA). Results: A significant elevation of ALT and AST enzymes was observed in HCV-NR. Besides, the PEG-IFN/RIB therapy in both MIG and MCP-1 in HCV-NR patients was significantly induced. PEGIFN/ RIB therapy significantly increased the levels of chemokines, such as IL-8, IP-10, EOTAXIN, MIG, RANTES, and MIP-1β, in HCV-R, indicating the chemokine response to PEG-IFN/RIB therapy. Conclusion: Hence, MCP-1 and MIG could be the potential biomarkers in HCV-NR and might be associated with the development of liver fibrosis, liver failure, and hepatocellular carcinoma. Limitations: Our study has only twenty samples of PEG-IFN/RIB treated HCV patients. This might be the reason for the lack of association between some of the inflammatory markers evaluated and the SVR, therefore, the association found between the chemokine levels observed in the plasma of HCV-R and HCV-NR and EVR cannot be extrapolated to patients infected with other HCV genotypes.

Background: The present study investigated the prevalence of Helicobacter pylori infection in peptic ulcer patients referred to the endoscopy departments in Khorramabad hospitals during 2013- 2016. Methods: The early pool of the study included all patients who had been referred to the endoscopy department and whose endoscopic and pathology reports were available and complete. After recording endoscopic reports, 1224 peptic ulcer (gastric or duodenal ulcer) cases, in which biopsy assays were performed to examine the type of ulcer and the presence of Helicobacter pylori bacteria, were selected. Pathology reports were collected by referring to the pathology departments. The information in the pathology report, including demographic information, was included in a pre-designed questionnaire to match the endoscopic reports, the location of the pathology sample, and other details, including the presence or absence of Helicobacter pylori bacteria. Finally, the data were analyzed using SPSS, version 21. Results: For all the 1224 patients studied, the mean age was 15.5 ± 17.5 years old. A total of 664 (54.2%) cases had gastric ulcers, 445 (36.4%) cases had duodenal ulcers, and 115 (9.4%) had both gastric and duodenal ulcers. Among gastric ulcer patients, 512 (65.7%) had a gastric ulcer in the antrum area, and 74.3% (579 patients) of the gastric ulcers were clean base type. Conclusion: The prevalence of infection was statistically significant in terms of the type, location, and number of peptic ulcers, including both gastric ulcer and duodenal ulcer.

Background: Rapid administration of appropriately indicated antibiotics is crucial in septic patients. Sepsis data supports that there is a higher risk of mortality for each hour delay from triage to antibiotic therapy, as well as for inappropriate antibiotic selection. There are a variety of rapid microbial detection systems, such as VERIGENE®, used in acute care facilities to rapidly detect bacteremia and identify resistance markers. Our study investigates the usefulness of VERIGENE® assays in accurately detecting Gram-positive and Gram-negative pathogens when compared to traditional blood culture analysis systems, such as VITEK®. Methods: 819 Gram-positive and 373 Gram-negative blood samples were collected and tested using both VERIGENE® and VITEK®. Statistical tests were two-tailed and observations were defined as statistically significant if P ≤ 0.05. Results: VERIGENE® detected a pathogen in 816/819 (99.6%) samples of the Gram-positive blood cultures and 367/373 (98.3%) samples of the Gram-negatives compared to 805/819 (98.3%) and 367/373 (98.4%), respectively, using VITEK®. Gram-positive cultures had a sensitivity of 99.5% and a specificity of 27.3% (PPV 99.0%, NPV 42.9%, 98.7% accuracy) with VERIGENE analysis. Gramnegatives had a sensitivity of 99.2% and a specificity of 20.0% (PPV 98.9%, NPV 25.0%, 98.4% accuracy). Conclusion: Although statistically insignificant (P = 0.25), VERIGENE® was 1.3% more likely to identify Gram-positive bacteria when compared to conventional methods. Overall, we concluded that VERIGENE® assays are valuable in their ability to rapidly detect microorganisms and resistance markers, given their high sensitivities. This allows for select targeted therapy in patients with sepsis and can ultimately reduce mortality rates.

Background: The higher mortality rate in COVID-19 patients is still a concern. Though some studies mention that elderly patients with co-morbidities are at higher risk of mortality, some others report uneventful outcomes in young patients even without co-morbidities. Secondary bacterial and fungal infections, especially with nosocomial pathogens are known to be associated with worse outcome in the ongoing pandemic as well as in the previous viral outbreaks. In such a scenario, the outcome of hospitalized COVID-19 patients can be improved by timely identification of secondary infections using appropriate biomarkers and by following appropriate infection control measures to prevent the spread of nosocomial pathogens. Objective: The study aims to find out the prevalence of bloodstream infections (BSI) among hospitalized COVID-19 patients and to analyze their laboratory markers and outcome by comparing them with those without BSI. Methods: In this descriptive cross-sectional study, the prevalence of secondary BSI was determined among the hospitalized COVID-19 patients by including 388 blood culture bottles collected from 293 patients, which were received in the microbiology lab within the study period. Results: The overall prevalence of BSI in COVID-19 patients was 39.5% (116/293), out of which 35.5% (104/293) infections were bacterial, and 4.1% (12/293) were fungal, while 8.9% (26/293) patients grew contaminants, and 51.5% (151/293) were sterile. Common causative agents of secondary BSI were found to be MDR Klebsiella pneumoniae (10.9%) and Acinetobacter baumannii (8.8%) followed by Candida species (4.1%). Patients with co-morbidities like diabetes, hypertension and COPD were at higher risk of developing BSI with significantly higher levels of sepsis markers such as Creactive protein (CRP), procalcitonin, ferritin and Interleukin-6 (IL-6). The mortality rate was significantly higher (60.2%) in patients with BSI compared to the group of patients without BSI. Conclusion: Our findings suggest the necessity of early diagnosis of the secondary infections using appropriate biomarkers and following proper infection control measures to prevent the spread of the nosocomial infections and improve the outcome of hospitalized COVID-19 patients.

Objective: This retrospective study aims to investigate the impact of tocilizumab on inflammatory markers in patients with severe COVID-19. The effect on oxygenation was also assessed. Methods: This study is a single-centre, retrospective cohort study conducted at NIMS hospital. Data of the eligible patients with severe COVID-19 pneumonia who received injection tocilizumab (max 800 mg) were charted and analysed. Oxygenation and inflammatory markers were compared before and after (day 3 and day 7) tocilizumab injection. Effect of dysglycemia on the efficacy of tocilizumab was assessed. Outcomes were analysed in the form of discharge without oxygen, discharge with oxygen, and death. Data were analysed by SPSS v22. Results: The mean age of the subjects was 57.8 ± 12.2 years, and 78.57% were male. Forty-four percent of the patient had type 2 diabetes. Tocilizumab treatment was associated with reduction in the oxygen requirement [median:10 L/min (IQR6- 14)] v/s 4 L/min (IQR 3-7, p-0.005]. Peripheral oxygen saturation also improved after tocilizumab [92 % (IQR 90-96)] v/s [95 % (IQR 94-96), p-0.01)], respectively. Serum CRP level decreased significantly when evaluated after three days (44±5 v/s 20 ±3 mg/dl, p=< 0.001). Out of the 42, 12 (29%) patients died due to severe COVID-19 or its complications. When compared with the patients who survived, patients who died had a higher level of D-dimer (1.2 ± 0.51 v/s 3.1 ±1.2 ng/dl, p-value- 0.04), and LDH: (845 ±55 v/s 1364 ±198 U/L, p - 0.01). At day seven of the tocilizumab injection, diabetic patients (n-13) had higher IL-6 serum level than nondiabetic patients (n-16) [(median- 311(IQR-1245.5) v/s (209 (IQR-546.2), p-value- 0.048]. Conclusion: In this retrospective pre-post analysis, tocilizumab injection was associated with reduced inflammation and improved oxygenation in severe COVID-19. Despite high IL-6 levels, diabetes had no impact on the efficacy of the tocilizumab.

Background: Superficial Pyogenic Infection (SPI) is the type of a pyogenic infection, which involves the infections of the skin, subcutaneous tissue, and soft tissue. These infections can cause significant morbidity. Antimicrobial Resistance (AMR) has emerged due to the rampant use of broadspectrum agents in superficial pyogenic infections. Objective: The aim of the study was to identify the microbial profile of superficial pyogenic infections and study their antimicrobial resistance. Methods: A cross-sectional observational study was carried out at the Department of Microbiology of a tertiary care hospital in the western region of Rajasthan. Samples included pus, aspirate from the abscess, necrotic tissue, and post-surgical drainage from infected skin at different sites of the patients attending OPD or admitted in IPD and ICU of the hospital. Identification of isolates was carried out by standard bacteriological techniques. The Antibiotic Susceptibility Testing (AST) of bacterial isolates was done by Kirby Bauer disk diffusion method on Mueller Hinton agar (HiMedia, India), and in a few cases, by automated Microscan system as recommended by the Clinical and Laboratory Standards Institute (CLSI), Wayne, USA. Results: A total of 2283 various specimens were obtained from different areas of healthcare facilities. Pathogenic bacterial isolates were recovered from 303 specimens. Staphylococcus aureus and Escherichia coli were found to be the main offenders. The effective antibiotics for gram-positive isolates were clindamycin, cotrimoxazole, linezolid, tetracycline, and vancomycin, and for gram-negative bacteria, meropenem, imipenem and amikacin were seen to be effective. Conclusion: This study can help formulate a local antibiotic policy which will restrict the unsupervised antibiotic use and strengthen antibiotic stewardship practices in the hospitals.

Background: Influenza is one of the most common infectious diseases, which affects the lower respiratory tract, and can lead to serious complications, including death. It is known that currently available therapeutic agents and vaccines do not provide 100% protection against influenza viruses. The development of drugs based on the RNA interference mechanism in the context of this problem is a promising area. This paper aims to assess the effect of FLT4, Nup98, and Nup205 cellular gene knockdown on the reproduction of the influenza A virus in human lung cell culture. Materials and Methods: Influenza virus strain A/WSN/1933 (St. Jude's Children's Research Hospital, USA) was used in this work as well as A549 cell culture (human lung adenocarcinoma, ATCC® CCL- 185, USA) and MDCK cell culture (dog kidney cells, Institut Pasteur, France). Small interfering RNAs (siRNAs) (Syntol, Russia) were synthesized for targeting the FLT4, Nup98, and Nup205 genes. Lipofectamin 2000 (Invitrogen, USA) was used for transfection. After 4 hours, the transfected cells were infected with the influenza virus at MOI = 0.1. Virus-containing fluid was collected within three days from the moment of transfection, and the intensity of viral reproduction was assessed by CPE titration and hemagglutination reactions. Viral RNA concentration was determined by RT-PCR. Mann- Whitney U test was used for statistical analysis. Results: In cells treated with siRNA for FLT4, Nup98, and Nup205 genes, there was a significant decrease in the expression of target genes and indicators of viral reproduction (virus titer, hemagglutinating activity, viral RNA concentration) at MOI = 0.1, although the cell survival rate did not decrease significantly. On the first day, the viral titer in cells treated with declared siRNA was lower, on average, by 1 Lg, and on the second and third days, by 2.2-2.3 Lg, compared to cells treated with nonspecific siRNA. During RT-PCR, a significant decrease in the concentration of viral RNA with Nup98.1 and Nup205 siRNA was detected: up to 190 times and 30 times on the first day, 26 and 29 times on the second day, and 6 and 30 times on the third day, respectively. For FLT4.2 siRNA, the number of viral RNA copies has been decreased by 23, 18, and 16 times on the first, second, and third days. Similar results were obtained while determining the hemagglutinating activity of the virus. The hemagglutinating activity decreased mostly (by 16 times) in cells treated with Nup205 and FLT4.2 siRNAs on the third day. In cells treated with FLT4.1, Nup98.1, and Nup98.2 siRNAs, the hemagglutinating activity decreased by 8 times. Conclusion: We identified a number of genes, such as FLT4, Nup98, and Nup205, whose expression can efficiently suppress viral reproduction when their expression is decreased. The original siRNA sequences were also obtained. These results are important for the creation of therapeutic and prophylactic agents, whose action is based on the RNA interference mechanism.

Background: In India, around 23.49 lac people have HIV/AIDS (PLHA). Strongyloidiasis and toxoplasmosis are some of the opportunistic infections that occur in HIV patients, but their dual coinfection with HIV is rarely reported. Case Presentation: A 46-year-old male was admitted to the hospital with generalized weakness, loss of weight, and bleeding per rectum for the last 3 months and a few episodes of dizziness and fever. Results: On routine investigation, he was diagnosed with human immunodeficiency virus (HIV) infection. On further evaluation, Toxoplasma gondii and Strongyloides stercoralis coinfection, as assessed by the parasitological diagnosis of the serum sample, was positive. Patient was started on artesunate, ART regimen (Tab, TLD- Dolutegravir 50 + Lamivudine 300 + Tenofovir DF 300) and cotrimoxazole. Conclusion: Herein, we report a case of Toxoplasma gondii and Strongyloides stercoralis coinfection in an immunocompromised patient.