Natural Product-inspired Antiviral Drug Discovery: A Systematic Review On The Multi-target Efficacy Of Plant...

Viral infections continue to pose a significant health problem to all parts of the world because of a high rate of mutation and the ability to resist traditional single-target antivirals. Multi-target inhibition of core viral proteins (main protease, RNA-dependent RNA polymerase, and spike glycoprotein) with plant metabolites as the target of drug discovery is a promising alternative. This review presented a systematic review of the antiviral potential and mechanism of plantderived compounds published from 2020 to 2025.

The systematic search of the literature was performed with the help of PubMed, Scopus, Web of Science, Science Direct, and EMBASE in accordance with PRISMA 2020. Peer-reviewed articles that reported precise molecular targets, quantifiable antiviral activity (IC50, EC50 or %inhibition), and mechanistic information were included. Qualitative synthesis of data was done because of heterogeneity in methodology.

Sixty studies were eligible. Flavonoids (quercetin, kaempferol) had an inhibitory effect on viral protease and polymerase with an IC50 value of 2-12 μM. The terpenoids (glycyrrhizin, betulinic acid) inhibited spike-ACE2 binding and viral fusion with up to 80% infectivity in vitro. The polymerases of hepatitis and influenza viruses were inhibited by polyphenols (EGCG, resveratrol). The bioavailability increased 150-200% with nano formulations, which enhanced therapeutic potency.

Metabolites of plants have direct antiviral and host immunomodulatory properties. Nevertheless, a lack of clinical validation and inconsistency in the standardization of phytochemicals are critical issues.

Plant-based metabolites are highly promising, multi-target antiviral leads. Nanotechnology, together with standardized pharmacological assessment and enhanced regulatory validation, has the potential to hasten clinical translation of plant metabolites into safe, broad-spectrum antiviral therapies.