Broad-spectrum antivirals from nature: studies on efficacy and molecular mechanism

Abstract

Viral diseases and their outbreaks continue to challenge our society. They are not only responsible for causing numerous infections but also disrupt the global economy and public health system. The recent COVID-19 pandemic was one of the most catastrophic event in human history that caused millions of fatalities worldwide. Enteroviruses are group of viruses that cause an array of diseases ranging from the mild, common cold to more severe infections like myocarditis and central nervous system infections. They are also associated with chronic infections such as type I diabetes. Currently, no antivirals have been clinically approved against enteroviruses and only one drug has been granted a conditional marketing authorization against coronaviruses by the European medicines agency (EMA). It has become important that one looks beyond the conventional routes and explore bioactive compounds from natural products to identify novel broad-spectrum antivirals. This study concentrates on the screening of different natural compounds for their antiviral potential against enteroviruses and coronaviruses and investigates their mechanism of action. We found broad-spectrum antiviral activity of Salix bark extract and Ganoderma sp. ferment against enveloped and non-enveloped viruses. These natural antivirals inhibited enteroviruses by stabilizing them and preventing their genome release. In contrast, the bark extract treatment led to disruption of coronaviruses. In addition, polyphenolic compounds also exhibited potent antiviral efficacy against enteroviruses and their efficacy was improved by several folds when they were functionalized on the surface of nanoparticles. Polyphenols inhibited the infection by binding at multiple sites on the virus capsid, leading to clustering and stabilization of the virus. Keywords: Coronavirus; enterovirus; natural antivirals; polyphenols; screening; stabilization