Potential of DNA Intercalating Alkaloids and Other Plant Secondary Metabolites against SARS-CoV-2 Causing COVID-19

Many plants produce secondary metabolites (PSMs) with antiviral activities. Among the antiviral PSMs, lipophilic terpenoids in essential oils can disturb the lipid envelope of viruses. Phenols and polyphenols (flavonoids, rosmarinic acid and tannins) attack viral proteins present in the viral membrane or inside the virus particle. Both phenolics and essential oils are active against free viral particles but not-or to a lesser degree-after a virus has entered a host cell. Another group of PSMs is directed against DNA or RNA. These are DNA intercalators such as sanguinarine, berberine, emetine and other isoquinoline alkaloids, ss-carboline, and quinoline alkaloids such as quinine, cinchonine, dictamine and skimmianine. The DNA intercalators stabilize double-stranded nucleic acids and inhibit the replication, transcription, and translation of genetic material. These alkaloids can inhibit viral development and viral replication in cells, as shown for SARS-CoV-1 and other viruses. Since chloroquine (which is also a DNA intercalator and a chemical derivative of the alkaloid quinine) is apparently clinically helpful against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, it is assumed that intercalating alkaloids, or the medicinal plants producing them, may be interesting candidates for the development of new antiviral drugs for the treatment of coronavirus disease 2019 (COVID-19).