A Review on Plant Bioactive Compounds and Their Modes of Action Against Coronavirus Infection

Abstract

The rapid outbreak of coronavirus disease 2019 (COVID-19) has demonstrated the need for development of new vaccine candidates and therapeutic drugs to fight against the underlying virus, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Currently, no antiviral treatment is available to treat COVID-19 as treatment is mostly directed to only relieving the symptoms. Retrospectively, herbal medicinal plants have been used for thousands of years as a medicinal alternative including for the treatment of various viral illnesses. However, a comprehensive description using various medicinal plants in treating coronavirus infection has not to date been described adequately, especially their modes of action. Most other reports and reviews have also only focused on selected ethnobotanical herbs such as Traditional Chinese Medicine, yet more plants can be considered to enrich the source of the anti-viral compounds. In this review, we have screened and identified potential herbal medicinal plants as anti-coronavirus medication across major literature databases without being limited to any regions or ethnobotanic criteria. As such we have successfully gathered experimentally validated in vivo, in vitro, or in silico findings of more than 30 plants in which these plant extracts or their related compounds, such as those of Artemisia annua L., Houttuynia cordata Thunb., and Sambucus formosana Nakai, are described through their respective modes of action against specific mechanisms or pathways during the viral infection. This includes inhibition of viral attachment and penetration, inhibition of viral RNA and protein synthesis, inhibition of viral key proteins such as 3-chymotrypsin-like cysteine protease (3CL^pro) and papain-like protease 2 (PL^pro), as well as other mechanisms including inhibition of the viral release and enhanced host immunity. We hope this compilation will help researchers and clinicians to identify the source of appropriate anti-viral drugs from plants in combating COVID-19 and, ultimately, save millions of affected human lives.

Keywords: COVID-19; SARS; Traditional Chinese medicine (TCM); drug; herb; medicinal plant; natural products; viral infection.

FIGURE 1

Mechanism of actions of antiviral agents/compounds from plants against coronavirus infection. As the virus initially infects an eukaryotic cell, several stages in the infection process occur which can be the potential sites of attack by the antiviral compounds. The life cycle of the virus begins when spike protein (S) of coronavirus binds to the angiotensin-converting enzyme 2 receptor (ACE2) located on the membrane of the host cells. The receptor binding facilitates viral envelope fusion with the host cell membrane before releasing the viral RNA into the host cell. The viral RNA encodes four structural proteins and two large non-structural polyproteins called ORF1a and ORF1b. These two non-structural polyproteins are translated and cleaved into 16 non-structural proteins (nsp) by two proteinases, 3-chymotrypsin-like cysteine protease (3CL^pro) and papain-like protease 2 (PL^pro). The yellow filled stars are the sites predicted to be cleaved by PLpro whereas the red filled stars are the sites predicted to be cleaved by 3CL^pro. Besides that, the coronavirus genome also encodes structural proteins, including spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins. After replication, transcription and translation, viral proteins and genome RNA are subsequently assembled into virions in the endoplasmic reticulum (ER) and Golgi body before they will be transported via vesicles to be released out of the cell as new virus progenies.

FIGURE 2

The chemical structure of bioactive compounds identified from plants that have inhibition effects on coronavirus infection.