Improving the Dissolution Rate and the Bioavailability of Favipiravir by Solid Dispersion with Curcumin

Favipiravir is an anti-viral agent that inhibits RNA-dependent RNA polymerase of several RNA viruses and is approved for the treatment of influenza in Japan. It has a role as an antiviral drug, an anti-coronaviral (COVID-19) agent but the poor solubility of the favipiravir in the aqueous media of the human body cause a reduction in the effectiveness and bioavailability. In the current work, the favipiravir was formulated for the first time as solid dispersed system with curcumin to improve dissolution property and antiviral activity during treatment of Covid-19. Binary and ternary mix of favipiravir and curcumin with/without soluplus were prepared and characterized by Differential Scanning Calorimetry (DSC), Powder X-ray Diffractometry (PXRD) and Fourier Transform Infrared Spec-troscopy (FTIR) and subjected to the dissolution test by apparatus I according to the European Pharma-copeia. The antiviral activity was measured by its cytotoxicity against A549-hACE2 cells. The results re-vealed that there was a reduction in the crystallinity of both binary and ternary mixtures with an en-hancement of the dissolution in comparison with the pure drug which accompanied by an improvement in the antiviral activity which is promising results that need further .Copyright © 2023, Colegio de Farmaceuticos de la Provincia de Buenos Aires. All rights reserved.

Resveratrol and Pterostilbene Inhibit SARS-CoV-2 Replication in Air-Liquid Interface Cultured Human Primary Bronchial Epithelial Cells.

The current COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has an enormous impact on human health and economy. In search for therapeutic options, researchers have proposed resveratrol, a food supplement with known antiviral, anti-inflammatory, and antioxidant properties as an advantageous antiviral therapy for SARS-CoV-2 infection. Here, we provide evidence that both resveratrol and its metabolically more stable structural analog, pterostilbene, exhibit potent antiviral properties against SARS-CoV-2 in vitro. First, we show that resveratrol and pterostilbene antiviral activity in African green monkey kidney cells. Both compounds actively inhibit virus replication within infected cells as reduced virus progeny production was observed when the compound was added at post-inoculation conditions. Without replenishment of the compound, antiviral activity was observed up to roughly five rounds of replication, demonstrating the long-lasting effect of these compounds. Second, as the upper respiratory tract represents the initial site of SARS-CoV-2 replication, we also assessed antiviral activity in air-liquid interface (ALI) cultured human primary bronchial epithelial cells, isolated from healthy volunteers. Resveratrol and pterostilbene showed a strong antiviral effect in these cells up to 48 h post-infection. Collectively, our data indicate that resveratrol and pterostilbene are promising antiviral compounds to inhibit SARS-CoV-2 infection. Because these results represent laboratory findings in cells, we advocate evaluation of these compounds in clinical trials before statements are made whether these drugs are advantageous for COVID-19 treatment.

Resveratrol-zinc nanoparticles or pterostilbene-zinc: Potential COVID-19 mono and adjuvant therapy.

In this manuscript we provide the scientific basis to adopt a novel combination of two widely available nutraceuticals; resveratrol and zinc in management of COVID-19 recommending their administration using a nano-carrier based drug-delivery system. Resveratrol, a well-known antioxidant and anti-inflammatory triphenolic stilbene, is abundant in red grapes, red wine, dark chocolate, and peanut butter. Alternatively, pterostilbene-zinc combination might be also considered without using a nano-carrier. We recommend conducting prompt clinical trials to assess the potential of the suggested combinations as a monotherapy for mild COVID-19 with a potential to prevent its progression to moderate-severe disease for which we recommend their trial as an adjuvant therapy. Furthermore, the suggested combinations might also possess a pharmacotherapeutic potential that exceeds COVID-19 to various inflammatory, immunologic, and oncologic diseases.