In Silico Analysis of Flavonoids From Crescentia cujete L. for Possible Antiviral Applications

Abstract

Introduction: Viruses, including the novel coronavirus responsible for the COVID-19 pandemic, continuously infect humans, causing illnesses of varying severity. Despite this, only a number of medicines were developed to counter some of these viruses and only preventive measures are being taken globally for some. This study explores the antiviral potential of flavonoids from Crescentia cujete. Methods: Molecular docking was performed on seven flavonoid compounds isolated from Crescentia cujete, targeting viral proteins associated with COVID-19 (Omicron and Delta variants), dengue, hepatitis C, Japanese encephalitis, and influenza A. The binding affinities of these compounds were calculated to determine the most effective antiviral interactions. Results: Docking simulations and absorption, distribution, metabolism, excretion, toxicity (ADMET) analyses identified naringenin as exhibiting the highest binding affinities against dengue (-10.44 kcal/mol) and COVID19 (-9.24 and -10.31 kcal/mol) Omicron and Delta variants. Luteolin demonstrated strong activity against Hepatitis C (-10.26 kcal/mol) and Influenza A (-8.4 kcal/mol), while pinocembrin showed optimal binding with Japanese Encephalitis protein (-10.6 kcal/mol). ADMET predictions indicated a low carcinogenic risk for pinocembrin and naringenin, highlighting their potential safety and efficacy. Conclusions: The seven identified flavonoids in Crescentia cujete exhibit promising antiviral properties, with superior docking scores and favourable ADMET profiles compared to certain commercial drugs. These flavonoids showed notable interactions with key viral proteins, with naringenin being the most active against the dengue and two COVID proteins, luteolin against hepatitis C and influenza A proteins, and pinocembrin against the Japanese encephalitis protein, suggesting these compounds as candidates for multitarget antiviral drug development.