Background and Aim: Viral infection dissemination and cytokine storm play an important role in the aggravation of COVID-19 disease, thus developing a drug that provides both antiviral and anti-inflammatory properties is essential. Method: In this study, we reviewed the remarkable properties of two major active compounds (hyperforin and hypericin) in Hypericum perforatum plant with a special focus on the molecular pathways that have been involved in their anti-inflammatory and antiviral effects. Results: Hyperforin can inhibit inflammation and regulate the function of the immune system by inhibiting the phosphorylation of three main signaling pathways including JAK/STAT, NF-κB, MAPK and increasing Treg cells. Hypericin by destruction of viral membrane, proteins, and nucleic acids can inactivate only enveloped viruses. Conclusion: Recently, studies have shown that hypericin has the ability to bind to the SARS-CoV- 2 NSP14, ACE2 recognition region of SARS-CoV-2\\\'s S-protein. The antiviral and anti- inflammatory properties of hypericin and hyperforin increase the probability of H. perforatum effectiveness against SARS-CoV-2. We believe that H. perforatum extract has the potential to be considered as an antiviral herbal medicine.

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