Síntese de flavonoides e avaliação da atividade inibitória sobre a COVID-19

Abstract

In late 2019, a viral outbreak originating in Wuhan, China, led to the COVID-19 pandemic, presenting unprecedented challenges to global public health. While agencies such as the U.S. Food and Drug Administration (FDA) and Brazil's National Health Surveillance Agency (ANVISA) have authorized certain treatments for COVID-19, these therapies often come with limitations, including drug interactions, the necessity for intravenous administration, and limited efficacy. Consequently, there is a pressing need for the development of more effective and accessible antiviral agents. In response to this need, collaborations between the pharmaceutical industry and academic institutions have increasingly employed Computer-Aided Drug Design (CADD). This approach facilitates the creation of bioactive compounds by analyzing the structures of molecular targets. A notable example is nafamostat mesylate, a serine protease inhibitor traditionally used for other indications, which has demonstrated the ability to inhibit SARS-CoV-2 replication by targeting the TMPRSS2 enzyme. Additionally, secondary metabolites such as flavonoids and capsaicinoids have shown potential antiviral properties. Flavonoids, widely found in various plants, exhibit antioxidant, anti-inflammatory, and antiviral activities. Capsaicinoids, have also demonstrated inhibitory effects against SARS-CoV-2. Given the significant health and economic impacts of the COVID-19 pandemic, this study aimed to synthesize compounds with potential antiviral activity using CADD methodologies. The proposed synthetic routes were designed to be straightforward, sustainable, and scalable. The study is organized into three chapters: the first discusses the pathology of SARS-CoV-2 and the global health emergency it precipitated; the second details the synthesis of capsaicin analogs derived from nafamostat mesylate; and the third presents findings related to flavonoid analogs and prospects for COVID-19.