Tackling the Future Pandemics: Broad-Spectrum Antiviral Agents (BSAAs) Based on A-Type Proanthocyanidins

Abstract

A-type proanthocyanidins (PAC-As) are plant-derived natural polyphenols that occur as oligomers or polymers of flavan-3-ol monomers, such as (+)-catechin and (−)-epicatechin, connected through an unusual double A linkage. PAC-As are present in leaves, seeds, flowers, bark, and fruits of many plants, and are thought to exert protective natural roles against microbial pathogens, insects, and herbivores. Consequently, when tested in isolation, PAC-As have shown several biological effects, through antioxidant, antibacterial, immunomodulatory, and antiviral activities. PAC-As have been observed in fact to inhibit replication of many different human viruses, and both enveloped and non-enveloped DNA and RNA viruses proved sensible to their inhibitory effect. Mechanistic studies revealed that PAC-As cause reduction of infectivity of viral particles they come in contact with, as a result of their propensity to interact with virion surface capsid proteins or envelope glycoproteins essential for viral attachment and entry. As viral infections and new virus outbreaks are a major public health concern, development of effective Broad-Spectrum Antiviral Agents (BSAAs) that can be rapidly deployable even against future emerging viruses is an urgent priority. This review summarizes the antiviral activities and mechanism of action of PAC-As, and their potential to be deployed as BSAAs against present and future viral infections.

The Flavonoid Cyanidin Shows Immunomodulatory and Broad-Spectrum Antiviral Properties, Including SARS-CoV-2

“…We should initiate comprehensive drug discovery programs for viruses that have pandemic potential, focusing on prototype pathogens. These approaches should prioritize drugs that act broadly against such virus families to provide protection against novel viruses that emerge, so they are poised to be trialed in infected patients when the next pandemic emerges [1,2].…”

“…Thus, these results indicated that A18 was able to inhibit the expression of some critical viral proteins and the viral RNA synthesis in the context of different virus infections. The antiviral action of several anthocyanidins has been associated with the inhibition of the virus adsorption to the cell surface [2]. Therefore, we decided to analyze whether A18 exerts its broad-spectrum antiviral activity through this mechanism of action.…”

“…On the other hand, the addition of A18 during virus internalization did not reduce viral infectivity (Figure 2). The antiviral action of several anthocyanidins has been associated with the inhibition of the virus adsorption to the cell surface [2]. Therefore, we decided to analyze whether A18 exerts its broad-spectrum antiviral activity through this mechanism of action.…”

“…Weight loss is a quantitative measurement of the severity of RSV infection in the murine BALB/c model [2,25]. A2 and Line 19 RSV-infected mice showed an early weight reduction on day 2 p.i., (Figure 5A,B) [18,[21][22][23][24].…”

“…New antiviral treatments are needed to deal with the unpredictable emergence of viruses. To minimize loss of life in future pandemics, we must prospectively produce broad-spectrum antiviral therapies for viruses with pandemic potential [1,2]. Despite many viral diseases causing significant mortality and morbidity in the population, vaccines and antivirals are only available for just a few viral infections, resulting in a great need for effective treatments.…”