Andrographis paniculata (Burm. F.) Wall. Ex Nees, Andrographolide, and Andrographolide Analogues as SARS-CoV-2 Antivirals? A Rapid Review

Abstract

Drug repurposing is commonly employed in the search for potential therapeutic agents. Andrographis paniculata, a medicinal plant commonly used for symptomatic relief of the common cold, and its phytoconstituent andrographolide, have been repeatedly identified as potential antivirals against SARS-CoV-2. In light of new evidence emerging since the onset of the COVID-19 pandemic, this rapid review was conducted to identify and evaluate the current SARS-CoV-2 antiviral evidence for A. paniculata, andrographolide, and andrographolide analogs. A systematic search and screen strategy of electronic databases and gray literature was undertaken to identify relevant primary articles. One target-based in vitro study reported the 3CLpro inhibitory activity of andrographolide as being no better than disulfiram. Another Vero cell-based study reported potential SARS-CoV-2 inhibitory activity for both andrographolide and A. paniculata extract. Eleven in silico studies predicted the binding of andrographolide and its analogs to several key antiviral targets of SARS-CoV-2 including the spike protein-ACE-2 receptor complex, spike protein, ACE-2 receptor, RdRp, 3CLpro, PLpro, and N-protein RNA-binding domain. In conclusion, in silico and in vitro studies collectively suggest multi-pathway targeting SARS-CoV-2 antiviral properties of andrographolide and its analogs, but in vivo data are needed to support these predictions.

A comprehensive review on disposition kinetics and dosage of oral administration of Andrographis paniculata, an alternative herbal medicine, in co-treatment of coronavirus disease

“…Angiotensin-converting enzyme 2 (ACE-2) has been identified as one of the main receptors to which the SARS-CoV-2 virus binds (Bourgonje et al, 2020). A previous in silico prediction found that a possible mechanism of A. paniculata's beneficial effects could involve the inhibition of this receptor (Lim et al, 2021). In addition, this study has predicted the binding of AP to antiviral targets, including the spike protein-ACE-2 receptor complex, spike protein, ACE-2 receptor, RdRp, 3CLpro, PLpro, and N-protein RNA-binding domain (Lim et al, 2021).…”

“…A previous in silico prediction found that a possible mechanism of A. paniculata's beneficial effects could involve the inhibition of this receptor (Lim et al, 2021). In addition, this study has predicted the binding of AP to antiviral targets, including the spike protein-ACE-2 receptor complex, spike protein, ACE-2 receptor, RdRp, 3CLpro, PLpro, and N-protein RNA-binding domain (Lim et al, 2021). The findings in these in silico studies imply that AP possesses multi-pathway targets contributing to its SARS-CoV-2 antiviral properties.…”

An insight into the pharmacological and analytical potential of Andrographolide

“…Andrographolide is found to exhibit a broad spectrum of anti-osteoclastogenesis [12], hepatopancreatic and gastroprotective [23], anti-allergic, anticancer and immunomodulatory, antihyperglycemic [24], antiosteoporosis, antioxidant [25], anti-inflammatory [26,27], antimicrobial, antiviral [28], antidiarrheal, and antimalarial activity [29,30], as shown in Figure 4. development of B16 melanoma cancer cells in immunocompetent C57BL/6 mice and HT-29 tumors in mouse models.…”

Andrographolide: A Herbal-Chemosynthetic Approach for Enhancing Immunity, Combating Viral Infections, and Its Implication on Human Health

“…Moreover, modulation of the immune response of these combo's (herbal-synthetic agents) and their interaction with specific receptors and cellular components are being actively studied, monitored, and the data reveal the addition of their beneficial application [94]. Drugs like Remdesivir, Hydroxychloroquine, Captopril, Nafamostat in combination with AGL constituents are established to have a good antiviral activity targeting ACE-2 receptor and spike protein complex, RdRp, PL pro , 3CL pro , N-protein RNA-binding domain of SARS-CoV-2 [95][96][97][98].…”