Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) - Volume 22, Issue 3, 2022

With severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) showing new characteristics and manifesting new variants, the efficacy of vaccination can be reduced. In the meanwhile, no SARS-CoV-2-specific drug has been introduced in the fight against coronavirus disease 2019 (COVID-19) yet, and currently used drugs have also shown serious side effects in patients under treatment. Thus, it is pivotal to continue researching potential therapeutics to treat COVID-19. Recently, studies have shown that Gallium maltolate disrupts the replication of SARS-CoV-2 and therefore has antiviral activity against this virus. Nevertheless, as Gallium compounds have manifested serious side effects in the human body (e.g., hemoglobin synthesis dysfunction and pulmonary complications), drug delivery methods should be recruited to minimize the possible side effects and to optimize the efficacy of the drug in the fight against COVID-19. Liposomes, as nanocarriers, not only increase the half-life of the conjugated compound but also have shown promising features in the delivery of COVID-19-specific drugs to the target tissue. Herein, we propose that conjugation of Gallium maltolate with liposome nanocarriers can be beneficial to target tissues infected with SARS-CoV-2.

The novel coronavirus, SARS-coV-2, which emerged in Wuhan in November 2019, has increasingly spread worldwide. More than 272 million cases of infection have been identified. COVID-19 has affected 223 countries and territories across the world. The principal target of the SARS-CoV-2 infection is the lower respiratory tract. Series of moderate to non-specific severe clinical signs and symptoms appear two to fourteen days after exposure to SARS-CoV-2 in patients with COVID-19 disease, including cough, breath deficiency, and at least two of these symptoms: headache, fever, chills, repeated rigor, myalgia, oropharyngitis, anosmia, and ageusia. No therapeutic agents have been validated to have substantial efficacy in the clinical care of COVID-19 patients in large-scale trials, despite worsening infected rates of COVID-19. Early clinical evidence from many sources suggests that treatment with famotidine may decrease COVID-19-related morbidity and mortality. The mechanism by which famotidine could improve the outcomes of COVID-19 is currently unknown. A more recent postulated mechanism is that the effect of famotidine is mediated by histamine-2 receptor antagonism or inverse agonism, inferring that the SARS-CoV-2, resulting in COVID-19 infection, at least partially leads to the abnormal release of histamine and perhaps dysfunction of mast cells.

The outbreak of COVID-19 that was first reported in Wuhan, China, has constituted a new emerging epidemic that has spread around the world. There are some reports illustrating the patients getting re-infected after recovering from COVID-19. Here, we provide an overview of the biphasic cycle of COVID-19, genetic diversity, immune response, and a chance of reinfection after recovering from COVID-19. The new generation of COVID-19 is a highly contagious and pathogenic infection that can lead to acute respiratory distress syndrome. Whilst most patients suffer from a mild form of the disease, there is a rising concern that patients who recover from COVID-19 may be at risk of reinfection. The proportion of the infected population is increasing worldwide; meanwhile, the rate and concern of reinfection by the recovered population are still high. Moreover, there is little evidence on the chance of COVID-19 infection even after vaccination, which is around one percent or less. Although the hypothesis of zero reinfections after vaccination has not been clinically proven, further studies should be performed on the recovered class in clusters to study the progression of the exposure with the re-exposed subpopulations to estimate the possibilities of reinfection and, thereby, advocate the use of these antibodies for vaccine creation.

Hantaviruses are rodent viruses that have been identified as etiologic agents of 2 diseases in humans: Hemorrhagic Fever with Renal Syndrome (HFRS) and Nephropathiaepidemica (NE) in the Old World and Hantavirus Pulmonary Syndrome (HPS) in the New World. Orthohantavirus is a genus of single-stranded, enveloped, negative-sense RNA viruses in the family Hantaviridae of the order Bunyavirales. The important reservoir of Hantaviruses is rodents. Each virus serotype has its unique rodent host species and is transmitted to human beings with the aid of aerosolized virus, which is shed in urine, faeces and saliva and hardly by a bite of the contaminated host. Andes virus is the only Hantavirus identified to be transmitted from human-to-human and its major signs and symptoms include fever, headache, muscle aches, lungs filled with fluid, etc. In early 1993, this viral syndrome appeared in the Four Corner location in the southwestern United States. The only accepted therapeutics for this virus is Ribavirin. Recently, serological examinations to identify Hantavirus antibodies have become most popular for investigation among humans and rodent reservoirs.

Background: Puerperal infection is used to describe any bacterial infection of the reproductive tract after delivery. Identifying the factors affecting postpartum infections can reduce the risk and complications of such factors and postpartum maternal mortality. Objective: This structured study was designed to evaluate factors affecting postpartum infections. Methods: In this study, after selecting Scopus, PubMed, SID, and Web of Science electronic databases, all observational studies (cohort and case-control) available and published in Farsi and English to investigate factors affecting postpartum infections were searched. The search was performed using the terms postpartum, infection, wound infection, puerperium, reason, risk factor, and their equivalent Persian words from 2010 to November 2019 regardless of publication status. Results: Out of the 3227 studies obtained, 19 were reviewed after removing irrelevant articles, duplicates (shared in databases), and animal samples. Age, level of education, delivery method, presence of episiotomy, anemia due to postpartum hemorrhage, interventions and manipulations during childbirth, prenatal hygiene, Povidone Iodine usage before delivery to wash the vagina, antibiotic prevention, increased labor duration, obesity, and the presence of bacteria were common symptoms affecting postpartum infection. Conclusion: In this study, the factors affecting postpartum infection have been identified, some of which are avoidable. Identifying these factors helps reduce postpartum infections and their complications.

Background: A safe and effective rubella vaccine is available and prescribed in IRAN. Objective: This is a survey of CRS cases collected based on WHO criteria one decade after the MR vaccination campaign (2003). Methods: This Multi-stage prospective/cross-sectional study was carried out in three stages in 3 educational hospitals in Tehran (Rasoul Aram, Akbar Abadi, and Firoozabadi), In the first stage of the study between 2011 and 2012 total of 186 infants were evaluated, and in the second stage of the study, total 163 blood samples of infants with suspected INTRA UTERINE INFECTION were compared with a group of healthy matched infants. In the first and second stages, Rubella immunity (IgG) in cord blood was evaluated by the Eliza method. Results: Despite MR vaccination in Iran, after one decade"confirmed CRS" and " compatible CRS" was diagnosed in 5 and 31 from 89 CRS suspected cases. Conclusion: The incidence of "confirmed CRS" in every 100 CRS suspected infants (after campaign) is 5.6 %, and 31 CRS Compatible cases are so important. Without active CRS surveillance, mild infection such as IUGR, hearing loss, heart abnormalities, impaired vision, and mental retardation even in the developed country might be missed. Fetal infection is persistent, which imposes additional costs on the country. Another mass vaccination in women and girls is needed. Also, the anti-rubella IgG testing before pregnancy in women who were not vaccinated; vaccination of women before marriage /pregnancy should be obligatory in order to prevent the CRS.

Background: Abaumannii baumannii rapidly resistant to a wide range of antimicrobial agents. The combination of Antimicrobial Photodynamic Therapy (aPDT) and Sonodynamic Antimicrobial Chemotherapy (SACT), known as Photo-Sonodynamic Antimicrobial Chemotherapy (PSACT), has received considerable attention as one of the emerging and promising strategies against microbial infections. Objective: This study aimed to investigate the antimicrobial effects of PSACT based on nano-micelle curcumin (N-MCur) on the virulence gene expression patterns in A. baumannii. Materials and Methods: N-MCur as a photo-sonosensitizer was synthesized and confirmed. To determine sub-significant reduction dose of PSACT, sub-significant reduction dose of N-MCur and blue laser light during aPDT, and ultrasound power output during SACT was assessed. Finally, changes in the expression of genes involved in treated A. baumannii by minimum sub-significant reduction dose of PSACT were determined using quantitative real-time-PCR (qRT-PCR). Results: PSACT using 12.5 mM N-MCur at the ultrasound power outputs of 28.7, 36.9, and 45.2 mW/cm² with 4 min irradiation time of the blue laser, as well as 6.2 mM N-MCur at an ultrasound power output of 45.2 mW/cm² plus 3 min blue laser irradiation time exhibited the significant dosedependent reduction against A. baumannii cell viability compared to the control group (P<0.05). After treatment of A. baumannii using 3.1 mM N-MCur + 2 min blue laser irradiation time + 28.7 mW/cm2 ultrasound as the minimum sub-significant reduction doses of PSACT, mRNA expression was significantly upregulated to 6.0-, 11.2-, and 13.7-folds in recA, blsA, and dnaK and downregulated to 8.6-, 10.1-, and 14.5-folds in csuE, espA, and abaI, respectively. Conclusion: N-MCur-mediated PSACT could regulate the expression of genes involved in A. baumannii pathogenesis. Therefore, PSACT can be proposed as a promising application to treat infections caused by A. baumannii.

Background: There is increasing evidence supporting a central role of the viral-induced hyper-inflammatory immune response in the pathogenesis of COVID-19. Serum procalcitonin (PCT) is an emerging prognostic marker in coronavirus disease 2019 (COVID-19). The aim of this study was to investigate the relationship between serum procalcitonin and clinical severity and outcomes in patients with coronavirus disease 2019 (COVID-19). Materials and Methods: Hematological and biochemical parameters were evaluated in patients with COVID-19 infection from February to April 2020 at Hajar Hospital in the Shahrekord University of Medical Science, Shahrekord, Iran. Results: The results showed that total lymphocyte counts, albumin, calcium, and creatinine levels were significantly different between the two moderate and severe groups, and the mean of procalcitonin level in COVID-19 patients with severe disease was higher (0.36 ng/mL) compared with the patients with moderate disease, and its level was found to be >5 ng/mL in 14.2% of5 ng/mL in 14.2% of patients in the former group. Conclusion: PCT may be a marker of disease severity in COVID-19 and may contribute to determining the severity of patients infected with SARS-CoV-2. Moreover, serial PCT measurements may be beneficial in predicting the prognosis.

Background: Coronavirus disease 2019 (COVID-19) has been recently declared as a global public health emergency, where the infection is caused by SARS-CoV-2. Nowadays, there is no specific treatment to cure this infection. The main protease (M^pro) of SARS-CoV-2 and SARS spike glycoprotein- human ACE2 complex have been recognized as suitable targets for treatment, including COVID-19 vaccines. Objective: In our current study, we identified the potential of Momordica charantia as a prospective alternative and a choice in dietary food during a pandemic. Materials and Methods: A total of 16 bioactive compounds of Momordica charantia were screened for activity against 6LU7 and 6CS2 with AutoDockVina. Results: We found that momordicoside B showed the lowest binding energy compared to other compounds. In addition, kuguaglycoside A and cucurbitadienol showed better profiles for drug-like properties based on Lipinski's rule of five. Conclusion: Our result indicates that these molecules can be further explored as promising candidates against SARS-CoV-2 or Momordica charantia can be used as one of the best food alternatives to be consumed during the pandemic.

Background: An impressive treatment for toxoplasmosis is the combinatory use of sulfadiazine and pyrimethamine. However, both the drugs involve significant side effects and toxicity for the host. Therefore, the discovery of new anti-toxoplasma medications with high efficacy and less to no side effects is urgently needed. Objective: This study aimed to evaluate the anti-toxoplasmic effects of Holothuria leucospilota (H. leucospilota) extract and TiO2NPs on the cell death of Toxoplasma gondii (T. gondii) tachyzoites in vitro and serum liver enzymes (AST, ALT, and ALP), and also to evaluate the immune response and production of IL-5, IFN-γ, and TNF-α in a mouse model. Materials and Methods: The cytotoxicity of TiO2NPs and H. leucospilota extract against the tachyzoite of T. gondii was evaluated by the methyl thiazolyl tetrazolium (MTT) assay. The levels of serum TNF-α, IFN-γ, IL-5, and liver enzymes were measured, as well. All the groups were subjected to T. gondii, and the survival rate of experimental mice was evaluated. Results: Our findings suggested in vivo and in vitro anti-toxoplasmic activity of TiO2NPs and H. leucospilota extract by inhibiting the proliferation and invasion of T. gondii tachyzoite. In addition, a significant increase in IFN-γ and TNF-α production was observed in mice treated with high doses of TiO2NPs and H. leucospilota extract. However, IL-5 levels decreased in TiO2NPs and H. leucospilota extract-treated mice. Our results also showed a highly significant increase (P < 0.05) in the levels of ALT, AST, and ALP in the groups injected with TiO2NPs and H. leucospilota extract, but not the control group. Conclusion: TiO2NPs and H. leucospilota extract have greater anti-toxoplasma effects in vitro and in vivo. These two compounds could be considered as a candidate for use against toxoplasmosis, both therapeutically and prophylactically.

Background: HPV tests have significant drawbacks in terms of detecting and differentiating types of the virus. PCR techniques provide timely and necessary results for patient care with high quality, sensitivity, and reasonable cost. Methods: The sensitivity of PCR depends on the primers. In this study, a method was designed that exploited PCR with designed primers (ScTd) by changing the annealing temperature (Ta) along with Sanger sequencing for pap smear samples. Sanger sequencing has confirmed that ScTd primers have a relative differentiation power using PCR. The primers caused a relative differentiation by PCR. In the pap smear sample 22 with contamination of types 16, 31, and 45, confirmed by dot blot hybridization, type 16 was not amplified at the specific Ta. Moreover, the band was observed at low Ta. Results: Sanger sequencing showed that type 16 was detected instead of type 52. Sequencing the heterozygous bands in multiple infections also led to the identification of different types. Moreover, with a combination of 7 pairs of primers, HPV types can be detected in multiple infections by PCR. Conclusion: As compared with the clinical dot blot hybridization technique, the utilization of complementary PCR and sequencing methods with designed primers can provide a higher positive predictive value in the detection of high-risk types.

Background: The novel coronavirus disease 2019 (COVID-19) has led to a global pandemic since its emergence from Wuhan, China, in December of 2019. As research continues to evolve, there is a paucity of reports describing the management and treatment of COVID-19 in patients with acute kidney failure and End-Stage Renal Disease (ESRD). These patients have increased susceptibility to developing severe clinical symptoms from SARS-CoV-2 infection due to their underlying comorbidities. Remdesivir has emerged as a promising antiviral drug against SARS-CoV-2. However, data regarding the clinical benefits of remdesivir in patients with severe renal impairment is unavailable as they have been excluded from clinical trials due to the risk of sulfobutylether-β-cyclodextrin (SBECD) accumulation in patients with eGFR<30 ml/min per 1.73m². Case Presentation: We present the first case of a 47-year-old male with end-stage renal disease who was successfully treated with remdesivir during hospitalization for acute respiratory distress syndrome and respiratory failure arising from COVID-19. The worsening clinical progress of the patient despite intensive care and treatment with intravenous azithromycin therapy led to the decision to utilize remdesivir after a risk-benefit analysis, despite his eGFR being <15 ml/min per 1.73m². Although the patient developed reversible hepatotoxicity, marked improvement of symptoms was observed after the five-day course of remdesivir was completed. Conclusion: Our findings describe the first instance of compassionate use of remdesivir for the treatment of COVID-19 in the setting of end-stage renal disease, acute respiratory distress syndrome, and hypoxemic respiratory failure.