Therapeutic Strategies for COVID-19 Patients: An Update.

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.

Antifungal Activity of Capric Acid, Nystatin, and Fluconazole and Their In Vitro Interactions Against Candida Isolates from Neonatal Oral Thrush.

Due to the increasing resistance of various Candida species to azole drugs, particularly fluconazole, it would be of significant importance to look for alternative therapies. The aim of this study was to investigate the antifungal activity of capric acid and its in vitro interactions with nystatin and fluconazole against Candida isolates. A total of 40 Candida isolates (C. albicans, 36; C. kefyr, 2; C. tropicalis, 1; C. glabrata, 1) collected from the oral cavity of neonates with oropharyngeal candidiasis and a reference strain of C. albicans (ATCC 10231) were used in this study. Antifungal activity of capric acid and two comparator antifungal drugs, namely fluconazole and nystatin, was tested according to CLSI M27-A3/M60 method. The in vitro interaction between capric acid with fluconazole and nystatin was determined following a checkerboard method and results were interpreted using fractional inhibitory concentration index. Nystatin had the lowest minimum inhibitory concentrations (range, 0.125-8 µg/mL; geometric mean [GM], 0.6229 µg/mL) followed by fluconazole (range, 0.5-16 µg/mL; GM, 1.9011 µg/mL) and capric acid (range, 128-2,048 µg/mL; GM, 835.9756 µg/mL). When tested in combination, capric acid with fluconazole demonstrated synergistic, indifferent, and antagonistic interactions in 3 (7.317%), 24 (58.536%), and 14 (34.146%) cases, respectively. For combination of capric acid with nystatin, synergistic, indifferent, and antagonistic interactions were observed in 1 (2.439%), 19 (46.341%), and 21 (51.219%) cases, respectively. All cases of synergistic interactions were against resistant or susceptible dose-dependent isolates. Fluconazole, nystatin, and capric acid seem to be more effective when they are used alone compared with their combination. However, their combination might be effective on resistant isolates.