Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) - Volume 22, Issue 6, 2022

The novel coronavirus SARS-coV-2, which emerged in Wuhan in November 2019, has increasingly spread, causing a global pandemic that infected more than 444 million people, resulting in severe social and economic ramifications, and claimed more than 6,010,000 lives by March 5, 2022. The pandemic attracted global attention with consequential multiple economic, social, and clinical studies. Among causes of poor clinical outcomes of the disease are therapeutic challenges, leading to spirals of studies in search of better therapeutic alternatives. Despite the worsening circumstances of the pandemic, no drug has yet shown remarkable efficacy in the clinical management of COVID-19 patients in large-scale trials. Many potential therapeutic strategies, including the use of nucleotide analogs, chloroquine phosphate, arbidol, protease inhibitors (lopinavir/ritonavir), plasma, monoclonal antibodies, plastic antibodies based on molecularly imprinted polymers (MIPs), traditional Chinese medicine (TCM), nanomaterials, vaccine, and mesenchymal stem cells (MSCs), have emerged with various degrees of successes. Remdesivir and dexamethasone have now been licensed based on the results of randomized controlled trials. Baricitinib, the Janus kinase (JAK) 1/2 inhibitor, is also an attractive candidate due to its properties as a potent anti-inflammatory agent and its hypothesized offtarget antiviral effects against SARS-CoV-2. Besides, human plasma from recovered COVID-19 patients is theoretically expected to be safe and effective for both therapy and post-exposure prophylaxis. In light of the literature, the correlation between the reduction of C5aR1/C5aR2 and the IL6-IL6R axis, using the available anti-IL6R mAb would be crucial. Moreover, MSCs are a potential therapeutic choice for patients with COVID-19 pneumonia. The coronavirus spike (S) protein that mediates the process of the infection via binding of host cells to the virus receptor is an essential focus for vaccine development. Importantly, with the number of patients increasing daily, there is an urgent need for effective therapeutic intervention. In this review, we expatiated on several strategies deployed for the treatment of COVID-19 infection.

Bacteriophages or phages are the most abundant organisms in the biosphere. Scientists considered phages an appropriate tool for understanding molecular biology, horizontal gene transfer vectors, stimulants of bacterial evolution, a source of diagnostic and genetic tools, and new therapeutic agents. Therefore, studying the biology of phages and their interactions with their hosts is crucial to gaining a deeper knowledge of biological systems. Numerous studies confirmed that bacteriophages are a genetic tool with high potential for treating infectious diseases, including bacterial, fungal, and viral infections. Therefore, phages may be used as an appropriate therapeutic target against some viruses, such as COVID-19 infection. In this study, we describe the role of phages in modulating the host immune system, the production of specific antibodies against the COVID-19 virus by the host immune system, and the minimization of damage caused by the COVID-19 virus to the host. Also, the present study expresses our understanding of the prospect of phage therapy as an adjunctive therapy.

After the first report of a coronavirus-associated pneumonia outbreak in December 2019, the virus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) that causes the infection/disease (COVID-19) has developed into a pandemic, with >100 million people infected in over 210 countries along with two million people deceased from COVID-19 till today. Coronaviruses are positivestranded RNA viruses having restricted RNA polymerase proofreading ability thus it is very genetically susceptible to mutation. The evolution of SARS-CoV-2 from a single-point zoonotic introduction in Wuhan in November or December 2019 was widely expected, and viral sequence surveillance was developed as a result. When the first sequence of SARS-CoV-2 was released, a race to develop vaccines started, and several vaccines are now used worldwide. Independent SARS-CoV-2 lineages have recently been identified in the UK (B.1.1.7), Brazil (P.1), South Africa (B.1.351), and India (B.1.617). The recent appearance of several SARS-CoV-2 variant strains has shattered faith in the modern generation of vaccines' ability to provide enduring defense against infection. The risk of escaping natural and induced immunity has encouraged an urgency to comprehend the implications of these improvements, as well as a drive to develop new approaches to combat SARS-CoV-2 variants.

Background: The use of herbs has recently been considered an effective method in the treatment of infections. The purpose of this study was to introduce Iranian medicinal plants with an effect on vaginal infections. Methods: In our systematic review study, keywords including ‘medicinal plants’, ‘Iranian medicinal plants’, ‘vaginal infection’, ‘essential oils’, and ‘extracts’ were searched in PubMed, Web of Science Direct, Scopus, Scientific Information Database, and Google Scholar. This study focused on the articles published from 2000 to 2019. Results and Discussion: According to our investigation, Stachys lavandulifolia, Thymus vulgaris L., Origanum vulgare L., Allium jesdianum, Cichorium intybus, Trigonella foenum-graecum, Azadirachta Indica, Stachys lavandulifolia, Coriandrum sativum L., Rosmarinus officinalis, Ferula gummosa L., Origanum syriacum, Eucalyptus globulus, Myrtus communis, Zingiber officinale, Punica granatum, Vitex agnus-castus, Mentha suaveolens, Quercus Brantii Lindl, Zataria multiflora, Berberis vulgaris, Thymus vulgaris L., Echinophora platyloba, Stachys lavandulifolia, Viola odorata, Menthe piperita, Eucalyptus camaldulensis, Ziziphus mauritiana, Quercus infectoria, Hypericum perforatum, Glycyrrhiza glabra L., Calendula officinalis, Origanum vulgare, Ziziphus nummularia, Satureja Bachtiarica, Foeniculum vulgare, Nigella sativa, Anethum graveolens, Salvia officinalis, and Calendula officinalis are used to treat vaginal infections. Conclusion: Therefore, native plants of Iran have been reported to have antimicrobial properties for the treatment of vaginal infections and can be used as a suitable and effective alternative to antibiotics in future research.

Background: Co-infection of schistosomiasis and malaria with hepatitis B virus (HBV) and hepatitis C virus (HCV) are common in countries where schistosomiasis and malaria are endemic. Objective: The present systematic review and meta-analysis was conducted to assess the prevalence of malaria/hepatitis viruses and Schistosoma/hepatitis viruses’ co-infections. Materials and Methods: Relevant published studies on the co-infection of malaria and Schistosoma spp. with HBV and HCV were retrieved via international databases (PubMed, Scopus, Web of Science, and Google Scholar). Regarding meta-analysis, the random128;effect model was employed by forest plot with a 95% of confidence interval (CI). Results: A total of 22 studies, including 15 studies with malaria/hepatitis viruses’ co-infection and 7 studies with Schistosoma/hepatitis viruses’ co-infection met the eligibility criteria. The co-infection of malaria/HCV and malaria/HBV in different populations were 15% (95% CI, 0-77%) and 5% (95% CI, 1-10%), respectively. Moreover, Schistosoma/HCV and Schistosoma/HBV co infection were detected in 7% (95% CI, 0-54%) and 2% (95% CI, 0-7%), respectively. Conclusion: The overlaps between Schistosoma spp. and malaria with hepatitis B and C viruses in endemic countries with lower income levels were high, which deserve further attention.

Background: In late December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), the causative agent of coronavirus disease 2019 (COVID-19), spread to almost all countries worldwide. The outbreak of this virus has been confirmed on 19th February, 2020, in Iran. Objective: The aim of this study was to investigate the time of viral RNA clearance in swab and serum samples of COVID-19 patients having received different medications. We also evaluated different factors that may affect viral RNA persistence in patients infected by SARS-CoV-2. Methods: In March 2020, twenty-one hospitalized COVID-19 patients participated in this prospective study. All patients received antiviral agents in their routine care. Throat swabs and blood samples were obtained from all patients in different intervals, including day 3 or 5, day 7, day 10, and finally, 14 days after the first positive real-time RT-PCR (rRT-PCT) test. Results: The median time from the symptom onset (SO) to the first negative rRT-PCR results for throat swabs and serum samples of COVID-19 patients was 18 and 14 days, respectively. These times were more significant in patients with lymphopenia, oxygen saturation ≤ 90%, and comorbidity. Conclusion: This preliminary study highlights that SASR-CoV-2 RNA was not detectable in the upper respiratory tract for longer than three weeks. In addition, SARS-CoV-2 may persist for a long period of time in the respiratory than in the serum samples. This study supports the idea that in limited resource settings, the patients should be tested earlier than three weeks for discharge management.

Background: In COVID-19, the respiratory tract is usually affected by SARS-CoV-2 infection. Due to viral transmission in the blood and an overwhelming inflammatory response, including cytokine storm, the condition can progress to acute respiratory distress syndrome and failure. Methylene blue is the only medicine that has been shown to reduce the excessive generation of reactive species and cytokines. Case Presentation: A 51-year-old male patient came to the hospital with shortness of breath. At room air, the patient was having 70% Spo2. The patient was treated with a noninvasive ventilator (NIV) and Standard of care (SOC). Due to prolonged hypoxia and respiratory distress, the patient was treated with NIV and the methylene blue (MB) was given in a humidifier for 5 days. Result: Methylene blue resulted in a significant decrease in respiratory distress and a steep rise in Spo2. Conclusion: We suggest trying methylene blue as an additional intervention in COVID-related acute respiratory distress to avoid the disease's devastating consequences.

Objective: Studies have indicated that hydroxychloroquine (HCQ) exerts antiviral effects against SARS-CoV-2 in vitro. However, trials regarding its effects on patients are very controversial. This study aims to evaluate the efficacy of (HCQ) in the treatment of hospitalized patients with COVID-19. Methods: We prospectively enrolled 260 patients hospitalized for COVID-19 in Heart and Brain Center of Excellence- Pleven, Bulgaria, for the period from November 6 to December 28, 2020. This study is not randomized, which we compensated for with Propensity Score Matching. Patients in the HCQ group were given HCQ 200 mg 3 times a day (600mg daily) for the duration of their hospitalization plus conventional treatment, while those in the control group were given conventional treatment only. The primary endpoints were transferred to the intensive care unit, needed for mechanical ventilation, and in-hospital death. Results: Of the 260 COVID-19 patients, 178 (68.5%) were male and the mean age was of 63.78 ± 12.45 years, with the most prevalent comorbidity hypertension (68.5%). We had two subgroups: treated with HCQ and conventional treatment (128 patients) and treated with conventional treatment only (132 patients). In the primary analysis, patients in the HCQ group presented with fewer comorbidities and were younger than the group without HCQ. Patients treated with HCQ demonstrated a significant benefit in the primary endpoints compared to those without HCQ, namely, transferred to ICU – 20 (20,8%) vs. 41 (36.9%), p=0.011, need for mechanical ventilation 13 (13.4%) vs. 33 (28.2%), p=0.009 and in-hospital death 14 (10.9%) vs. 35 (26.5%), p=0,001, respectively. We repeated this analysis with PSM, where 70 matched pairs were identified. Regarding the primary endpoints, we found again a statistically significant difference between the groups. Comparing transferring to ICU, better outcomes were presented in the HCQ group: 8 (17.4%) vs. 27 (44.3%), with p= 0.003. Besides, a smaller proportion of the patients needed mechanical ventilation: 6 (12.8%), compared to the control group, 23 (35.4%), p= 0.007. Notably, patients from the HCQ group died during hospitalization: 8 (11.4%) in comparison with 19 (27.1%) from the control group, p= 0.018. Conclusion: Patients treated with HCQ demonstrated a significant benefit in the primary endpoints in our study, namely, transfer to the intensive care unit, need for mechanical ventilation, and in-hospital death. HCQ improves prognosis in hospitalized patients with COVID-19.

Background: Coronavirus disease 2019 (COVID-19) was caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and patients with COVID-19 may be treated with traditional medicine like Ayurveda alone or in combination with standard allopathic treatment, as Ayurveda is one of the oldest traditional medicinal systems followed by millions around the world. Methods: The literature was searched in databases such as LitCOVID, Google Scholar, Science Direct, EBSCO, Scopus, Web of Science, EMBASE, and reference lists to identify articles relevant to the use of Ayurvedic medicines in the management of COVID-19. Results: Several clinical studies have determined the efficacy of Ayurvedic medicines and formulations in the management of patients with COVID-19. Conclusion: The Ayurvedic medicines and formulations with antiviral, antioxidant, anti-inflammatory, and immunomodulatory properties could be used along with standard allopathic medicines to assist in the earlier detection of virus, speedy recovery of patients with COVID-19, faster discharge from hospitals, and the prevention of further deterioration.

Background: Leishmaniasis, caused by the Leishmania parasite, is one of the most important tropical neglected diseases. The urgent search for effective, inexpensive, and preferably herbal anti-leishmanial agents, is needed. Objective: Curcumin is a natural polyphenolic compound derived from turmeric that is well known for its antioxidant, anti-inflammatory, anti-tumor, and anti-cancer activity. Methods: The present work evaluates the anti-leishmanial [Leishmania major] activity of curcumin. The infected PBMCs were treated with curcumin. The ROS level at 6, 12, 24 h and gene expression levels at 24, 48, and 72 h of PBMCs after treatment with curcumin were determined. Results: Based on the results, the curcumin concentrations of 268 μM [24 h] and 181.2 μM [72 h] were defined as IC50 against L. major promastigotes. Treatment of L. major infected-peripheral blood mononuclear cells [PBMCs] with IC50 concentrations of curcumin, depending on exposure time, significantly induced the reactive oxygen species [ROS] generation and increased the expression levels of interferongamma [IFN-γ], tumor necrosis factor-alpha [TNF-α], and nitric oxide synthase [iNOS] genes. Conclusion: These findings suggest the potential of curcumin against Leishmaniasis.